Neurodevelopmental and Epilepsy Phenotypes in Individuals With Missense Variants in the Voltage-Sensing and Pore Domains of KCNH5 .

Autor:	Happ HC; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Sadleir LG; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Zemel M; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., de Valles-Ibáñez G; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Hildebrand MS; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., McConkie-Rosell A; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., McDonald M; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., May H; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Sands T; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Aggarwal V; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Elder C; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Feyma T; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Bayat A; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Møller RS; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Fenger CD; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Klint Nielsen JE; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Datta AN; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Gorman KM; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., King MD; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Linhares ND; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Burton BK; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Paras A; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Ellard S; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Rankin J; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Shukla A; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Majethia P; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Olson RJ; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Muthusamy K; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Schimmenti LA; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Starnes K; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Sedláčková L; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Štěrbová K; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Vlčková M; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Laššuthová P; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Jahodová A; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Porter BE; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Couque N; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Colin E; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Prouteau C; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Collet C; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Smol T; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Caumes R; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Vansenne F; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Bisulli F; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Licchetta L; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Person R; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Torti E; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., McWalter K; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Webster R; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Gerard EE; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Lesca G; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Szepetowski P; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Scheffer IE; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Mefford HC; These authors contributed equally as first authors.; †These authors contributed equally as senior authors.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL., Carvill GL; These authors contributed equally as first authors. gemma.carvill@northwestern.edu.; †These authors contributed equally as senior authors. gemma.carvill@northwestern.edu.; From the Ken and Ruth Davee Department of Neurology (K.C.H., E.E.G., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; University of Otago (L.G.S.), Wellington, New Zealand; University of Washington (M.Z.), Seattle; Department of Medicine (G.d.V.-I., R.W., I.E.S.), Epilepsy Research Centre, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia; Duke University Medical Center (A.M.-R., M.M.), Durham, NC; Institute for Genomic Medicine (H.M., T.S.), Columbia University Irving Medical Center, New York, NY; Departments of Pathology and Cell Biology (V.A.), and Neurology (C.E.), Columbia University Irving Medical Center, New York, NY; Gillette Children's Specialty Healthcare (T.F.), St. Paul, MN; Department of Epilepsy Genetics and Personalized Medicine (A.B., R.S.M., C.D.F.), Danish Epilepsy Center, Dianalund, Denmark; Institute of Regional Health Research (A.B., R.S.M.), University of Southern Denmark; Amplexa Genetics (C.D.F.), Odense, Denmark; Department of Clinical Medicine (J.E.K.N.), Zealand University Hospital, Roskilde, Denmark; University of British Columbia (A.N.D.), Vancouver, Canada; The Department of Neurology and Clinical Neurophysiology (K.M.G., M.D.K.), Children's Health Ireland at Temple St., Dublin 1, Ireland; School of Medicine and Medical Science (K.M.G., M.D.K.), University College Dublin, Ireland; Genuity Science (N.L.), Dublin, Ireland; Ann & Robert H. Lurie Children's Hospital of Chicago (B.K.B., A.P.), Chicago, IL; Department of Pediatrics (B.K.B., A.P., G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL; Exeter Genomics Laboratory (S.E.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Institute of Clinical and Biomedical Science (S.E.), University of Exeter, United Kingdom; Department Clinical Genetics (J.R.), Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom; Department of Medical Genetics (A.S., P.M.), Kasturba Medical College, Manipal, Manipal Academy of Higher Education, India; Center for Individualized Medicine (R.J.O., K.M., L.A.S.), Mayo Clinic, Rochester, MN; Departments of Clinical Genomics (K.M., L.A.S.), and Neurology (K.S.), Mayo Clinic, Rochester, MN; Neurogenetic Laboratory (L.S., P.J.), Department of Pediatric Neurology, Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Epilepsy Research Centre Prague-EpiReC Consortium (L.S., K.S., M.V., P.L., A.J.); Motol University Hospital is a full member of the ERN EpiCARE; Department of Pediatric Neurology (K.S., A.J.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Biology and Medical Genetics (M.V.), Second Faculty of Medicine, Charles University in Prague and Motol University Hospital, Czech Republic; Stanford University School of Medicine (B.E.P.), Palo Alto, CA; Laboratoire de Biologie médicale multisites Seqoia-FMG2025 (N.C., C.C.), Laboratoire Génétique Moléculaire Robert-Debré, Paris, France; Service de Génétique (E.C., C.P.), CHU d'Angers, Angers, France; University Lille (T.S.), CHU Lille, ULR7364-RADEME, Institut de Genetique Medicale, France; University Lille (R.C.), CHU Lille, ULR7364-RADEME, Clinique de Genetique, France; Univeristy Medical Center Groningen (F.V.), Groningen, the Netherlands; Department of Biomedical and NeuroMotor Sciences (F.B.), University of Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna (F.B., L.L.), Full Member of the ERN EpiCARE Bologna, Italy; GeneDx (R.P., E.T., K.M.), Gaithersburg, MD; T.Y. Nelson Department of Neurology and Neurosurgery (R.W.), Children's Hospital at Westmead, Westmead, New South Wales, Australia; Department of Medical Genetics (G.L.), University Hospital of Lyon, Claude Bernard Lyon 1 University, France; INSERM, Aix-Marseille University (P.S.), INMED, France; Department of Neurology (I.E.S.), Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, and Murdoch Children's Research Institute, Parkville, Victoria, Australia; The Florey Institute of Neuroscience and Mental Health (I.E.S.), Victoria, Australia; Center for Pediatric Neurological Disease Research (H.C.M.), St. Jude Children's Research Hospital, Memphis, TN; and Department of Pharmacology (G.L.C.), Northwestern University Feinberg School of Medicine, Chicago, IL. gemma.carvill@northwestern.edu.
Jazyk:	angličtina
Zdroj:	Neurology [Neurology] 2023 Feb 07; Vol. 100 (6), pp. e603-e615. Date of Electronic Publication: 2022 Oct 28.
DOI:	10.1212/WNL.0000000000201492
Abstrakt:	Background and Objectives: KCNH5 encodes the voltage-gated potassium channel EAG2/Kv10.2. We aimed to delineate the neurodevelopmental and epilepsy phenotypic spectrum associated with de novo KCNH5 variants. Methods: We screened 893 individuals with developmental and epileptic encephalopathies for KCNH5 variants using targeted or exome sequencing. Additional individuals with KCNH5 variants were identified through an international collaboration. Clinical history, EEG, and imaging data were analyzed; seizure types and epilepsy syndromes were classified. We included 3 previously published individuals including additional phenotypic details. Results: We report a cohort of 17 patients, including 9 with a recurrent de novo missense variant p.Arg327His, 4 with a recurrent missense variant p.Arg333His, and 4 additional novel missense variants. All variants were located in or near the functionally critical voltage-sensing or pore domains, absent in the general population, and classified as pathogenic or likely pathogenic using the American College of Medical Genetics and Genomics criteria. All individuals presented with epilepsy with a median seizure onset at 6 months. They had a wide range of seizure types, including focal and generalized seizures. Cognitive outcomes ranged from normal intellect to profound impairment. Individuals with the recurrent p.Arg333His variant had a self-limited drug-responsive focal or generalized epilepsy and normal intellect, whereas the recurrent p.Arg327His variant was associated with infantile-onset DEE. Two individuals with variants in the pore domain were more severely affected, with a neonatal-onset movement disorder, early-infantile DEE, profound disability, and childhood death. Discussion: We describe a cohort of 17 individuals with pathogenic or likely pathogenic missense variants in the voltage-sensing and pore domains of Kv10.2, including 14 previously unreported individuals. We present evidence for a putative emerging genotype-phenotype correlation with a spectrum of epilepsy and cognitive outcomes. Overall, we expand the role of EAG proteins in human disease and establish KCNH5 as implicated in a spectrum of neurodevelopmental disorders and epilepsy. (© 2022 American Academy of Neurology.)
Databáze:	MEDLINE
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