Therapeutic Role of Nusinersen on Respiratory Progression in Pediatric Patients With Spinal Muscular Atrophy Type 2 and Nonambulant Type 3.

Autor:	Trucco F; Dubowitz Neuromuscular Centre (FT, HW, MS, AR, MLM, GB, FM), UCL Institute of Child Health & Great Ormond Street Hospital, London; Department Paediatric Neuroscience Evelina London Children's Hospital and Department Paediatric Respiratory Medicine (FT), Royal Brompton Hospital, Guy's and St Thomas NHS Trust London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (FT), IRCCS Istituto Giannina Gaslini, Genova and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Italy; Population (DR), Policy and Practice Programme, UCL GOS Institute of Child Health, London; Paediatric Neurology (GC, RDS, MP, MCP, EM), Università Cattolica del Sacro Cuore; Centro Clinico Nemo (GC, RDS, MP, MCP, EM), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Newcastle University and Newcastle Hospitals NHS Foundation Trust (AGM, CM-B), Newcastle Upon Tyne, United Kingdom; Department of Rehabilitation and Regenerative Medicine (JM), Columbia University Irving Medical Center, New York; Neurorehabilitation Unit (VAS, EA), University of Milan, Neuromuscular Omnicentre Clinical Center, Niguarda Hospital; Unit of Neuromuscular and Neurodegenerative Disorders (ADA, ESB), Bambino Gesù Children's Hospital IRCCS, Rome; Center of Experimental and Translational Myology (CB), IRCCS Istituto Giannina Gaslini, Genoa and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa; Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud (SSM), University of Messina, Italy; Leeds Children Hospital (A-MC); The Robert Jones and Agnes Hunt Orthopaedic Hospital (TW), Oswestry; Sheffield Children's Hospital (MTO, LS); MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre (LS), University of Oxford, United Kingdom; Neuromuscular Reference Center, Department of Paediatrics, University and University Hospital of Liege, Belgium; Royal Hospital for Children (AM), Bristol; Royal Manchester Children's Hospital (IH); University Hospitals Birmingham (DP), United Kingdom; Evelina London Children's Hospital (VLG), London, UK; Departments of Neurology and Pediatrics (DCDV), Columbia University Irving Medical Center, New York; Department of Neurology (BTD), Boston Children's Hospital, Harvard Medical School, Boston, MA; Department of Neurology (JWD), Stanford University, Palo Alto, CA; Department of Paediatrics The Children's Hospital of Philadelphia (OM, ZZ-C), Philadelphia, PA; Nemours Children's Hospital (RSF), University of Central Florida College of Medicine, Orlando; St. Jude Children's Research Hospital (RSF), Memphis, TN; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), London, United Kingdom., Ridout D; Dubowitz Neuromuscular Centre (FT, HW, MS, AR, MLM, GB, FM), UCL Institute of Child Health & Great Ormond Street Hospital, London; Department Paediatric Neuroscience Evelina London Children's Hospital and Department Paediatric Respiratory Medicine (FT), Royal Brompton Hospital, Guy's and St Thomas NHS Trust London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (FT), IRCCS Istituto Giannina Gaslini, Genova and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Italy; Population (DR), Policy and Practice Programme, UCL GOS Institute of Child Health, London; Paediatric Neurology (GC, RDS, MP, MCP, EM), Università Cattolica del Sacro Cuore; Centro Clinico Nemo (GC, RDS, MP, MCP, EM), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Newcastle University and Newcastle Hospitals NHS Foundation Trust (AGM, CM-B), Newcastle Upon Tyne, United Kingdom; Department of Rehabilitation and Regenerative Medicine (JM), Columbia University Irving Medical Center, New York; Neurorehabilitation Unit (VAS, EA), University of Milan, Neuromuscular Omnicentre Clinical Center, Niguarda Hospital; Unit of Neuromuscular and Neurodegenerative Disorders (ADA, ESB), Bambino Gesù Children's Hospital IRCCS, Rome; Center of Experimental and Translational Myology (CB), IRCCS Istituto Giannina Gaslini, Genoa and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa; Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud (SSM), University of Messina, Italy; Leeds Children Hospital (A-MC); The Robert Jones and Agnes Hunt Orthopaedic Hospital (TW), Oswestry; Sheffield Children's Hospital (MTO, LS); MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre (LS), University of Oxford, United Kingdom; Neuromuscular Reference Center, Department of Paediatrics, University and University Hospital of Liege, Belgium; Royal Hospital for Children (AM), Bristol; Royal Manchester Children's Hospital (IH); University Hospitals Birmingham (DP), United Kingdom; Evelina London Children's Hospital (VLG), London, UK; Departments of Neurology and Pediatrics (DCDV), Columbia University Irving Medical Center, New York; Department of Neurology (BTD), Boston Children's Hospital, Harvard Medical School, Boston, MA; Department of Neurology (JWD), Stanford University, Palo Alto, CA; Department of Paediatrics The Children's Hospital of Philadelphia (OM, ZZ-C), Philadelphia, PA; Nemours Children's Hospital (RSF), University of Central Florida College of Medicine, Orlando; St. Jude Children's Research Hospital (RSF), Memphis, TN; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), London, United Kingdom., Weststrate H; Dubowitz Neuromuscular Centre (FT, HW, MS, AR, MLM, GB, FM), UCL Institute of Child Health & Great Ormond Street Hospital, London; Department Paediatric Neuroscience Evelina London Children's Hospital and Department Paediatric Respiratory Medicine (FT), Royal Brompton Hospital, Guy's and St Thomas NHS Trust London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (FT), IRCCS Istituto Giannina Gaslini, Genova and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Italy; Population (DR), Policy and Practice Programme, UCL GOS Institute of Child Health, London; Paediatric Neurology (GC, RDS, MP, MCP, EM), Università Cattolica del Sacro Cuore; Centro Clinico Nemo (GC, RDS, MP, MCP, EM), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Newcastle University and Newcastle Hospitals NHS Foundation Trust (AGM, CM-B), Newcastle Upon Tyne, United Kingdom; Department of Rehabilitation and Regenerative Medicine (JM), Columbia University Irving Medical Center, New York; Neurorehabilitation Unit (VAS, EA), University of Milan, Neuromuscular Omnicentre Clinical Center, Niguarda Hospital; Unit of Neuromuscular and Neurodegenerative Disorders (ADA, ESB), Bambino Gesù Children's Hospital IRCCS, Rome; Center of Experimental and Translational Myology (CB), IRCCS Istituto Giannina Gaslini, Genoa and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa; Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud (SSM), University of Messina, Italy; Leeds Children Hospital (A-MC); The Robert Jones and Agnes Hunt Orthopaedic Hospital (TW), Oswestry; Sheffield Children's Hospital (MTO, LS); MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre (LS), University of Oxford, United Kingdom; Neuromuscular Reference Center, Department of Paediatrics, University and University Hospital of Liege, Belgium; Royal Hospital for Children (AM), Bristol; Royal Manchester Children's Hospital (IH); University Hospitals Birmingham (DP), United Kingdom; Evelina London Children's Hospital (VLG), London, UK; Departments of Neurology and Pediatrics (DCDV), Columbia University Irving Medical Center, New York; Department of Neurology (BTD), Boston Children's Hospital, Harvard Medical School, Boston, MA; Department of Neurology (JWD), Stanford University, Palo Alto, CA; Department of Paediatrics The Children's Hospital of Philadelphia (OM, ZZ-C), Philadelphia, PA; Nemours Children's Hospital (RSF), University of Central Florida College of Medicine, Orlando; St. Jude Children's Research Hospital (RSF), Memphis, TN; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), London, United Kingdom., Scoto M; Dubowitz Neuromuscular Centre (FT, HW, MS, AR, MLM, GB, FM), UCL Institute of Child Health & Great Ormond Street Hospital, London; Department Paediatric Neuroscience Evelina London Children's Hospital and Department Paediatric Respiratory Medicine (FT), Royal Brompton Hospital, Guy's and St Thomas NHS Trust London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (FT), IRCCS Istituto Giannina Gaslini, Genova and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Italy; Population (DR), Policy and Practice Programme, UCL GOS Institute of Child Health, London; Paediatric Neurology (GC, RDS, MP, MCP, EM), Università Cattolica del Sacro Cuore; Centro Clinico Nemo (GC, RDS, MP, MCP, EM), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Newcastle University and Newcastle Hospitals NHS Foundation Trust (AGM, CM-B), Newcastle Upon Tyne, United Kingdom; Department of Rehabilitation and Regenerative Medicine (JM), Columbia University Irving Medical Center, New York; Neurorehabilitation Unit (VAS, EA), University of Milan, Neuromuscular Omnicentre Clinical Center, Niguarda Hospital; Unit of Neuromuscular and Neurodegenerative Disorders (ADA, ESB), Bambino Gesù Children's Hospital IRCCS, Rome; Center of Experimental and Translational Myology (CB), IRCCS Istituto Giannina Gaslini, Genoa and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa; Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud (SSM), University of Messina, Italy; Leeds Children Hospital (A-MC); The Robert Jones and Agnes Hunt Orthopaedic Hospital (TW), Oswestry; Sheffield Children's Hospital (MTO, LS); MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre (LS), University of Oxford, United Kingdom; Neuromuscular Reference Center, Department of Paediatrics, University and University Hospital of Liege, Belgium; Royal Hospital for Children (AM), Bristol; Royal Manchester Children's Hospital (IH); University Hospitals Birmingham (DP), United Kingdom; Evelina London Children's Hospital (VLG), London, UK; Departments of Neurology and Pediatrics (DCDV), Columbia University Irving Medical Center, New York; Department of Neurology (BTD), Boston Children's Hospital, Harvard Medical School, Boston, MA; Department of Neurology (JWD), Stanford University, Palo Alto, CA; Department of Paediatrics The Children's Hospital of Philadelphia (OM, ZZ-C), Philadelphia, PA; Nemours Children's Hospital (RSF), University of Central Florida College of Medicine, Orlando; St. Jude Children's Research Hospital (RSF), Memphis, TN; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), London, United Kingdom., Rohwer A; Dubowitz Neuromuscular Centre (FT, HW, MS, AR, MLM, GB, FM), UCL Institute of Child Health & Great Ormond Street Hospital, London; Department Paediatric Neuroscience Evelina London Children's Hospital and Department Paediatric Respiratory Medicine (FT), Royal Brompton Hospital, Guy's and St Thomas NHS Trust London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (FT), IRCCS Istituto Giannina Gaslini, Genova and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Italy; Population (DR), Policy and Practice Programme, UCL GOS Institute of Child Health, London; Paediatric Neurology (GC, RDS, MP, MCP, EM), Università Cattolica del Sacro Cuore; Centro Clinico Nemo (GC, RDS, MP, MCP, EM), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Newcastle University and Newcastle Hospitals NHS Foundation Trust (AGM, CM-B), Newcastle Upon Tyne, United Kingdom; Department of Rehabilitation and Regenerative Medicine (JM), Columbia University Irving Medical Center, New York; Neurorehabilitation Unit (VAS, EA), University of Milan, Neuromuscular Omnicentre Clinical Center, Niguarda Hospital; Unit of Neuromuscular and Neurodegenerative Disorders (ADA, ESB), Bambino Gesù Children's Hospital IRCCS, Rome; Center of Experimental and Translational Myology (CB), IRCCS Istituto Giannina Gaslini, Genoa and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa; Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud (SSM), University of Messina, Italy; Leeds Children Hospital (A-MC); The Robert Jones and Agnes Hunt Orthopaedic Hospital (TW), Oswestry; Sheffield Children's Hospital (MTO, LS); MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre (LS), University of Oxford, United Kingdom; Neuromuscular Reference Center, Department of Paediatrics, University and University Hospital of Liege, Belgium; Royal Hospital for Children (AM), Bristol; Royal Manchester Children's Hospital (IH); University Hospitals Birmingham (DP), United Kingdom; Evelina London Children's Hospital (VLG), London, UK; Departments of Neurology and Pediatrics (DCDV), Columbia University Irving Medical Center, New York; Department of Neurology (BTD), Boston Children's Hospital, Harvard Medical School, Boston, MA; Department of Neurology (JWD), Stanford University, Palo Alto, CA; Department of Paediatrics The Children's Hospital of Philadelphia (OM, ZZ-C), Philadelphia, PA; Nemours Children's Hospital (RSF), University of Central Florida College of Medicine, Orlando; St. Jude Children's Research Hospital (RSF), Memphis, TN; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), London, United Kingdom., Coratti G; Dubowitz Neuromuscular Centre (FT, HW, MS, AR, MLM, GB, FM), UCL Institute of Child Health & Great Ormond Street Hospital, London; Department Paediatric Neuroscience Evelina London Children's Hospital and Department Paediatric Respiratory Medicine (FT), Royal Brompton Hospital, Guy's and St Thomas NHS Trust London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (FT), IRCCS Istituto Giannina Gaslini, Genova and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Italy; Population (DR), Policy and Practice Programme, UCL GOS Institute of Child Health, London; Paediatric Neurology (GC, RDS, MP, MCP, EM), Università Cattolica del Sacro Cuore; Centro Clinico Nemo (GC, RDS, MP, MCP, EM), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Newcastle University and Newcastle Hospitals NHS Foundation Trust (AGM, CM-B), Newcastle Upon Tyne, United Kingdom; Department of Rehabilitation and Regenerative Medicine (JM), Columbia University Irving Medical Center, New York; Neurorehabilitation Unit (VAS, EA), University of Milan, Neuromuscular Omnicentre Clinical Center, Niguarda Hospital; Unit of Neuromuscular and Neurodegenerative Disorders (ADA, ESB), Bambino Gesù Children's Hospital IRCCS, Rome; Center of Experimental and Translational Myology (CB), IRCCS Istituto Giannina Gaslini, Genoa and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa; Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud (SSM), University of Messina, Italy; Leeds Children Hospital (A-MC); The Robert Jones and Agnes Hunt Orthopaedic Hospital (TW), Oswestry; Sheffield Children's Hospital (MTO, LS); MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre (LS), University of Oxford, United Kingdom; Neuromuscular Reference Center, Department of Paediatrics, University and University Hospital of Liege, Belgium; Royal Hospital for Children (AM), Bristol; Royal Manchester Children's Hospital (IH); University Hospitals Birmingham (DP), United Kingdom; Evelina London Children's Hospital (VLG), London, UK; Departments of Neurology and Pediatrics (DCDV), Columbia University Irving Medical Center, New York; Department of Neurology (BTD), Boston Children's Hospital, Harvard Medical School, Boston, MA; Department of Neurology (JWD), Stanford University, Palo Alto, CA; Department of Paediatrics The Children's Hospital of Philadelphia (OM, ZZ-C), Philadelphia, PA; Nemours Children's Hospital (RSF), University of Central Florida College of Medicine, Orlando; St. Jude Children's Research Hospital (RSF), Memphis, TN; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), London, United Kingdom., Main ML; Dubowitz Neuromuscular Centre (FT, HW, MS, AR, MLM, GB, FM), UCL Institute of Child Health & Great Ormond Street Hospital, London; Department Paediatric Neuroscience Evelina London Children's Hospital and Department Paediatric Respiratory Medicine (FT), Royal Brompton Hospital, Guy's and St Thomas NHS Trust London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (FT), IRCCS Istituto Giannina Gaslini, Genova and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Italy; Population (DR), Policy and Practice Programme, UCL GOS Institute of Child Health, London; Paediatric Neurology (GC, RDS, MP, MCP, EM), Università Cattolica del Sacro Cuore; Centro Clinico Nemo (GC, RDS, MP, MCP, EM), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Newcastle University and Newcastle Hospitals NHS Foundation Trust (AGM, CM-B), Newcastle Upon Tyne, United Kingdom; Department of Rehabilitation and Regenerative Medicine (JM), Columbia University Irving Medical Center, New York; Neurorehabilitation Unit (VAS, EA), University of Milan, Neuromuscular Omnicentre Clinical Center, Niguarda Hospital; Unit of Neuromuscular and Neurodegenerative Disorders (ADA, ESB), Bambino Gesù Children's Hospital IRCCS, Rome; Center of Experimental and Translational Myology (CB), IRCCS Istituto Giannina Gaslini, Genoa and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa; Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud (SSM), University of Messina, Italy; Leeds Children Hospital (A-MC); The Robert Jones and Agnes Hunt Orthopaedic Hospital (TW), Oswestry; Sheffield Children's Hospital (MTO, LS); MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre (LS), University of Oxford, United Kingdom; Neuromuscular Reference Center, Department of Paediatrics, University and University Hospital of Liege, Belgium; Royal Hospital for Children (AM), Bristol; Royal Manchester Children's Hospital (IH); University Hospitals Birmingham (DP), United Kingdom; Evelina London Children's Hospital (VLG), London, UK; Departments of Neurology and Pediatrics (DCDV), Columbia University Irving Medical Center, New York; Department of Neurology (BTD), Boston Children's Hospital, Harvard Medical School, Boston, MA; Department of Neurology (JWD), Stanford University, Palo Alto, CA; Department of Paediatrics The Children's Hospital of Philadelphia (OM, ZZ-C), Philadelphia, PA; Nemours Children's Hospital (RSF), University of Central Florida College of Medicine, Orlando; St. Jude Children's Research Hospital (RSF), Memphis, TN; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), London, United Kingdom., Mayhew AG; Dubowitz Neuromuscular Centre (FT, HW, MS, AR, MLM, GB, FM), UCL Institute of Child Health & Great Ormond Street Hospital, London; Department Paediatric Neuroscience Evelina London Children's Hospital and Department Paediatric Respiratory Medicine (FT), Royal Brompton Hospital, Guy's and St Thomas NHS Trust London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (FT), IRCCS Istituto Giannina Gaslini, Genova and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Italy; Population (DR), Policy and Practice Programme, UCL GOS Institute of Child Health, London; Paediatric Neurology (GC, RDS, MP, MCP, EM), Università Cattolica del Sacro Cuore; Centro Clinico Nemo (GC, RDS, MP, MCP, EM), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Newcastle University and Newcastle Hospitals NHS Foundation Trust (AGM, CM-B), Newcastle Upon Tyne, United Kingdom; Department of Rehabilitation and Regenerative Medicine (JM), Columbia University Irving Medical Center, New York; Neurorehabilitation Unit (VAS, EA), University of Milan, Neuromuscular Omnicentre Clinical Center, Niguarda Hospital; Unit of Neuromuscular and Neurodegenerative Disorders (ADA, ESB), Bambino Gesù Children's Hospital IRCCS, Rome; Center of Experimental and Translational Myology (CB), IRCCS Istituto Giannina Gaslini, Genoa and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa; Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud (SSM), University of Messina, Italy; Leeds Children Hospital (A-MC); The Robert Jones and Agnes Hunt Orthopaedic Hospital (TW), Oswestry; Sheffield Children's Hospital (MTO, LS); MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre (LS), University of Oxford, United Kingdom; Neuromuscular Reference Center, Department of Paediatrics, University and University Hospital of Liege, Belgium; Royal Hospital for Children (AM), Bristol; Royal Manchester Children's Hospital (IH); University Hospitals Birmingham (DP), United Kingdom; Evelina London Children's Hospital (VLG), London, UK; Departments of Neurology and Pediatrics (DCDV), Columbia University Irving Medical Center, New York; Department of Neurology (BTD), Boston Children's Hospital, Harvard Medical School, Boston, MA; Department of Neurology (JWD), Stanford University, Palo Alto, CA; Department of Paediatrics The Children's Hospital of Philadelphia (OM, ZZ-C), Philadelphia, PA; Nemours Children's Hospital (RSF), University of Central Florida College of Medicine, Orlando; St. Jude Children's Research Hospital (RSF), Memphis, TN; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), London, United Kingdom., Montes J; Dubowitz Neuromuscular Centre (FT, HW, MS, AR, MLM, GB, FM), UCL Institute of Child Health & Great Ormond Street Hospital, London; Department Paediatric Neuroscience Evelina London Children's Hospital and Department Paediatric Respiratory Medicine (FT), Royal Brompton Hospital, Guy's and St Thomas NHS Trust London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (FT), IRCCS Istituto Giannina Gaslini, Genova and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Italy; Population (DR), Policy and Practice Programme, UCL GOS Institute of Child Health, London; Paediatric Neurology (GC, RDS, MP, MCP, EM), Università Cattolica del Sacro Cuore; Centro Clinico Nemo (GC, RDS, MP, MCP, EM), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Newcastle University and Newcastle Hospitals NHS Foundation Trust (AGM, CM-B), Newcastle Upon Tyne, United Kingdom; Department of Rehabilitation and Regenerative Medicine (JM), Columbia University Irving Medical Center, New York; Neurorehabilitation Unit (VAS, EA), University of Milan, Neuromuscular Omnicentre Clinical Center, Niguarda Hospital; Unit of Neuromuscular and Neurodegenerative Disorders (ADA, ESB), Bambino Gesù Children's Hospital IRCCS, Rome; Center of Experimental and Translational Myology (CB), IRCCS Istituto Giannina Gaslini, Genoa and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa; Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud (SSM), University of Messina, Italy; Leeds Children Hospital (A-MC); The Robert Jones and Agnes Hunt Orthopaedic Hospital (TW), Oswestry; Sheffield Children's Hospital (MTO, LS); MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre (LS), University of Oxford, United Kingdom; Neuromuscular Reference Center, Department of Paediatrics, University and University Hospital of Liege, Belgium; Royal Hospital for Children (AM), Bristol; Royal Manchester Children's Hospital (IH); University Hospitals Birmingham (DP), United Kingdom; Evelina London Children's Hospital (VLG), London, UK; Departments of Neurology and Pediatrics (DCDV), Columbia University Irving Medical Center, New York; Department of Neurology (BTD), Boston Children's Hospital, Harvard Medical School, Boston, MA; Department of Neurology (JWD), Stanford University, Palo Alto, CA; Department of Paediatrics The Children's Hospital of Philadelphia (OM, ZZ-C), Philadelphia, PA; Nemours Children's Hospital (RSF), University of Central Florida College of Medicine, Orlando; St. Jude Children's Research Hospital (RSF), Memphis, TN; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), London, United Kingdom., De Sanctis R; Dubowitz Neuromuscular Centre (FT, HW, MS, AR, MLM, GB, FM), UCL Institute of Child Health & Great Ormond Street Hospital, London; Department Paediatric Neuroscience Evelina London Children's Hospital and Department Paediatric Respiratory Medicine (FT), Royal Brompton Hospital, Guy's and St Thomas NHS Trust London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (FT), IRCCS Istituto Giannina Gaslini, Genova and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Italy; Population (DR), Policy and Practice Programme, UCL GOS Institute of Child Health, London; Paediatric Neurology (GC, RDS, MP, MCP, EM), Università Cattolica del Sacro Cuore; Centro Clinico Nemo (GC, RDS, MP, MCP, EM), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Newcastle University and Newcastle Hospitals NHS Foundation Trust (AGM, CM-B), Newcastle Upon Tyne, United Kingdom; Department of Rehabilitation and Regenerative Medicine (JM), Columbia University Irving Medical Center, New York; Neurorehabilitation Unit (VAS, EA), University of Milan, Neuromuscular Omnicentre Clinical Center, Niguarda Hospital; Unit of Neuromuscular and Neurodegenerative Disorders (ADA, ESB), Bambino Gesù Children's Hospital IRCCS, Rome; Center of Experimental and Translational Myology (CB), IRCCS Istituto Giannina Gaslini, Genoa and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa; Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud (SSM), University of Messina, Italy; Leeds Children Hospital (A-MC); The Robert Jones and Agnes Hunt Orthopaedic Hospital (TW), Oswestry; Sheffield Children's Hospital (MTO, LS); MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre (LS), University of Oxford, United Kingdom; Neuromuscular Reference Center, Department of Paediatrics, University and University Hospital of Liege, Belgium; Royal Hospital for Children (AM), Bristol; Royal Manchester Children's Hospital (IH); University Hospitals Birmingham (DP), United Kingdom; Evelina London Children's Hospital (VLG), London, UK; Departments of Neurology and Pediatrics (DCDV), Columbia University Irving Medical Center, New York; Department of Neurology (BTD), Boston Children's Hospital, Harvard Medical School, Boston, MA; Department of Neurology (JWD), Stanford University, Palo Alto, CA; Department of Paediatrics The Children's Hospital of Philadelphia (OM, ZZ-C), Philadelphia, PA; Nemours Children's Hospital (RSF), University of Central Florida College of Medicine, Orlando; St. Jude Children's Research Hospital (RSF), Memphis, TN; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), London, United Kingdom., Pane M; Dubowitz Neuromuscular Centre (FT, HW, MS, AR, MLM, GB, FM), UCL Institute of Child Health & Great Ormond Street Hospital, London; Department Paediatric Neuroscience Evelina London Children's Hospital and Department Paediatric Respiratory Medicine (FT), Royal Brompton Hospital, Guy's and St Thomas NHS Trust London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (FT), IRCCS Istituto Giannina Gaslini, Genova and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Italy; Population (DR), Policy and Practice Programme, UCL GOS Institute of Child Health, London; Paediatric Neurology (GC, RDS, MP, MCP, EM), Università Cattolica del Sacro Cuore; Centro Clinico Nemo (GC, RDS, MP, MCP, EM), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Newcastle University and Newcastle Hospitals NHS Foundation Trust (AGM, CM-B), Newcastle Upon Tyne, United Kingdom; Department of Rehabilitation and Regenerative Medicine (JM), Columbia University Irving Medical Center, New York; Neurorehabilitation Unit (VAS, EA), University of Milan, Neuromuscular Omnicentre Clinical Center, Niguarda Hospital; Unit of Neuromuscular and Neurodegenerative Disorders (ADA, ESB), Bambino Gesù Children's Hospital IRCCS, Rome; Center of Experimental and Translational Myology (CB), IRCCS Istituto Giannina Gaslini, Genoa and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa; Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud (SSM), University of Messina, Italy; Leeds Children Hospital (A-MC); The Robert Jones and Agnes Hunt Orthopaedic Hospital (TW), Oswestry; Sheffield Children's Hospital (MTO, LS); MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre (LS), University of Oxford, United Kingdom; Neuromuscular Reference Center, Department of Paediatrics, University and University Hospital of Liege, Belgium; Royal Hospital for Children (AM), Bristol; Royal Manchester Children's Hospital (IH); University Hospitals Birmingham (DP), United Kingdom; Evelina London Children's Hospital (VLG), London, UK; Departments of Neurology and Pediatrics (DCDV), Columbia University Irving Medical Center, New York; Department of Neurology (BTD), Boston Children's Hospital, Harvard Medical School, Boston, MA; Department of Neurology (JWD), Stanford University, Palo Alto, CA; Department of Paediatrics The Children's Hospital of Philadelphia (OM, ZZ-C), Philadelphia, PA; Nemours Children's Hospital (RSF), University of Central Florida College of Medicine, Orlando; St. Jude Children's Research Hospital (RSF), Memphis, TN; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), London, United Kingdom., Pera MC; Dubowitz Neuromuscular Centre (FT, HW, MS, AR, MLM, GB, FM), UCL Institute of Child Health & Great Ormond Street Hospital, London; Department Paediatric Neuroscience Evelina London Children's Hospital and Department Paediatric Respiratory Medicine (FT), Royal Brompton Hospital, Guy's and St Thomas NHS Trust London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (FT), IRCCS Istituto Giannina Gaslini, Genova and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Italy; Population (DR), Policy and Practice Programme, UCL GOS Institute of Child Health, London; Paediatric Neurology (GC, RDS, MP, MCP, EM), Università Cattolica del Sacro Cuore; Centro Clinico Nemo (GC, RDS, MP, MCP, EM), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Newcastle University and Newcastle Hospitals NHS Foundation Trust (AGM, CM-B), Newcastle Upon Tyne, United Kingdom; Department of Rehabilitation and Regenerative Medicine (JM), Columbia University Irving Medical Center, New York; Neurorehabilitation Unit (VAS, EA), University of Milan, Neuromuscular Omnicentre Clinical Center, Niguarda Hospital; Unit of Neuromuscular and Neurodegenerative Disorders (ADA, ESB), Bambino Gesù Children's Hospital IRCCS, Rome; Center of Experimental and Translational Myology (CB), IRCCS Istituto Giannina Gaslini, Genoa and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa; Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud (SSM), University of Messina, Italy; Leeds Children Hospital (A-MC); The Robert Jones and Agnes Hunt Orthopaedic Hospital (TW), Oswestry; Sheffield Children's Hospital (MTO, LS); MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre (LS), University of Oxford, United Kingdom; Neuromuscular Reference Center, Department of Paediatrics, University and University Hospital of Liege, Belgium; Royal Hospital for Children (AM), Bristol; Royal Manchester Children's Hospital (IH); University Hospitals Birmingham (DP), United Kingdom; Evelina London Children's Hospital (VLG), London, UK; Departments of Neurology and Pediatrics (DCDV), Columbia University Irving Medical Center, New York; Department of Neurology (BTD), Boston Children's Hospital, Harvard Medical School, Boston, MA; Department of Neurology (JWD), Stanford University, Palo Alto, CA; Department of Paediatrics The Children's Hospital of Philadelphia (OM, ZZ-C), Philadelphia, PA; Nemours Children's Hospital (RSF), University of Central Florida College of Medicine, Orlando; St. Jude Children's Research Hospital (RSF), Memphis, TN; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), London, United Kingdom., Sansone VA; Dubowitz Neuromuscular Centre (FT, HW, MS, AR, MLM, GB, FM), UCL Institute of Child Health & Great Ormond Street Hospital, London; Department Paediatric Neuroscience Evelina London Children's Hospital and Department Paediatric Respiratory Medicine (FT), Royal Brompton Hospital, Guy's and St Thomas NHS Trust London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (FT), IRCCS Istituto Giannina Gaslini, Genova and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Italy; Population (DR), Policy and Practice Programme, UCL GOS Institute of Child Health, London; Paediatric Neurology (GC, RDS, MP, MCP, EM), Università Cattolica del Sacro Cuore; Centro Clinico Nemo (GC, RDS, MP, MCP, EM), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Newcastle University and Newcastle Hospitals NHS Foundation Trust (AGM, CM-B), Newcastle Upon Tyne, United Kingdom; Department of Rehabilitation and Regenerative Medicine (JM), Columbia University Irving Medical Center, New York; Neurorehabilitation Unit (VAS, EA), University of Milan, Neuromuscular Omnicentre Clinical Center, Niguarda Hospital; Unit of Neuromuscular and Neurodegenerative Disorders (ADA, ESB), Bambino Gesù Children's Hospital IRCCS, Rome; Center of Experimental and Translational Myology (CB), IRCCS Istituto Giannina Gaslini, Genoa and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa; Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud (SSM), University of Messina, Italy; Leeds Children Hospital (A-MC); The Robert Jones and Agnes Hunt Orthopaedic Hospital (TW), Oswestry; Sheffield Children's Hospital (MTO, LS); MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre (LS), University of Oxford, United Kingdom; Neuromuscular Reference Center, Department of Paediatrics, University and University Hospital of Liege, Belgium; Royal Hospital for Children (AM), Bristol; Royal Manchester Children's Hospital (IH); University Hospitals Birmingham (DP), United Kingdom; Evelina London Children's Hospital (VLG), London, UK; Departments of Neurology and Pediatrics (DCDV), Columbia University Irving Medical Center, New York; Department of Neurology (BTD), Boston Children's Hospital, Harvard Medical School, Boston, MA; Department of Neurology (JWD), Stanford University, Palo Alto, CA; Department of Paediatrics The Children's Hospital of Philadelphia (OM, ZZ-C), Philadelphia, PA; Nemours Children's Hospital (RSF), University of Central Florida College of Medicine, Orlando; St. Jude Children's Research Hospital (RSF), Memphis, TN; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), London, United Kingdom., Albamonte E; Dubowitz Neuromuscular Centre (FT, HW, MS, AR, MLM, GB, FM), UCL Institute of Child Health & Great Ormond Street Hospital, London; Department Paediatric Neuroscience Evelina London Children's Hospital and Department Paediatric Respiratory Medicine (FT), Royal Brompton Hospital, Guy's and St Thomas NHS Trust London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (FT), IRCCS Istituto Giannina Gaslini, Genova and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Italy; Population (DR), Policy and Practice Programme, UCL GOS Institute of Child Health, London; Paediatric Neurology (GC, RDS, MP, MCP, EM), Università Cattolica del Sacro Cuore; Centro Clinico Nemo (GC, RDS, MP, MCP, EM), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Newcastle University and Newcastle Hospitals NHS Foundation Trust (AGM, CM-B), Newcastle Upon Tyne, United Kingdom; Department of Rehabilitation and Regenerative Medicine (JM), Columbia University Irving Medical Center, New York; Neurorehabilitation Unit (VAS, EA), University of Milan, Neuromuscular Omnicentre Clinical Center, Niguarda Hospital; Unit of Neuromuscular and Neurodegenerative Disorders (ADA, ESB), Bambino Gesù Children's Hospital IRCCS, Rome; Center of Experimental and Translational Myology (CB), IRCCS Istituto Giannina Gaslini, Genoa and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa; Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud (SSM), University of Messina, Italy; Leeds Children Hospital (A-MC); The Robert Jones and Agnes Hunt Orthopaedic Hospital (TW), Oswestry; Sheffield Children's Hospital (MTO, LS); MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre (LS), University of Oxford, United Kingdom; Neuromuscular Reference Center, Department of Paediatrics, University and University Hospital of Liege, Belgium; Royal Hospital for Children (AM), Bristol; Royal Manchester Children's Hospital (IH); University Hospitals Birmingham (DP), United Kingdom; Evelina London Children's Hospital (VLG), London, UK; Departments of Neurology and Pediatrics (DCDV), Columbia University Irving Medical Center, New York; Department of Neurology (BTD), Boston Children's Hospital, Harvard Medical School, Boston, MA; Department of Neurology (JWD), Stanford University, Palo Alto, CA; Department of Paediatrics The Children's Hospital of Philadelphia (OM, ZZ-C), Philadelphia, PA; Nemours Children's Hospital (RSF), University of Central Florida College of Medicine, Orlando; St. Jude Children's Research Hospital (RSF), Memphis, TN; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), London, United Kingdom., D'Amico A; Dubowitz Neuromuscular Centre (FT, HW, MS, AR, MLM, GB, FM), UCL Institute of Child Health & Great Ormond Street Hospital, London; Department Paediatric Neuroscience Evelina London Children's Hospital and Department Paediatric Respiratory Medicine (FT), Royal Brompton Hospital, Guy's and St Thomas NHS Trust London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (FT), IRCCS Istituto Giannina Gaslini, Genova and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Italy; Population (DR), Policy and Practice Programme, UCL GOS Institute of Child Health, London; Paediatric Neurology (GC, RDS, MP, MCP, EM), Università Cattolica del Sacro Cuore; Centro Clinico Nemo (GC, RDS, MP, MCP, EM), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Newcastle University and Newcastle Hospitals NHS Foundation Trust (AGM, CM-B), Newcastle Upon Tyne, United Kingdom; Department of Rehabilitation and Regenerative Medicine (JM), Columbia University Irving Medical Center, New York; Neurorehabilitation Unit (VAS, EA), University of Milan, Neuromuscular Omnicentre Clinical Center, Niguarda Hospital; Unit of Neuromuscular and Neurodegenerative Disorders (ADA, ESB), Bambino Gesù Children's Hospital IRCCS, Rome; Center of Experimental and Translational Myology (CB), IRCCS Istituto Giannina Gaslini, Genoa and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa; Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud (SSM), University of Messina, Italy; Leeds Children Hospital (A-MC); The Robert Jones and Agnes Hunt Orthopaedic Hospital (TW), Oswestry; Sheffield Children's Hospital (MTO, LS); MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre (LS), University of Oxford, United Kingdom; Neuromuscular Reference Center, Department of Paediatrics, University and University Hospital of Liege, Belgium; Royal Hospital for Children (AM), Bristol; Royal Manchester Children's Hospital (IH); University Hospitals Birmingham (DP), United Kingdom; Evelina London Children's Hospital (VLG), London, UK; Departments of Neurology and Pediatrics (DCDV), Columbia University Irving Medical Center, New York; Department of Neurology (BTD), Boston Children's Hospital, Harvard Medical School, Boston, MA; Department of Neurology (JWD), Stanford University, Palo Alto, CA; Department of Paediatrics The Children's Hospital of Philadelphia (OM, ZZ-C), Philadelphia, PA; Nemours Children's Hospital (RSF), University of Central Florida College of Medicine, Orlando; St. Jude Children's Research Hospital (RSF), Memphis, TN; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), London, United Kingdom., Bruno C; Dubowitz Neuromuscular Centre (FT, HW, MS, AR, MLM, GB, FM), UCL Institute of Child Health & Great Ormond Street Hospital, London; Department Paediatric Neuroscience Evelina London Children's Hospital and Department Paediatric Respiratory Medicine (FT), Royal Brompton Hospital, Guy's and St Thomas NHS Trust London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (FT), IRCCS Istituto Giannina Gaslini, Genova and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Italy; Population (DR), Policy and Practice Programme, UCL GOS Institute of Child Health, London; Paediatric Neurology (GC, RDS, MP, MCP, EM), Università Cattolica del Sacro Cuore; Centro Clinico Nemo (GC, RDS, MP, MCP, EM), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Newcastle University and Newcastle Hospitals NHS Foundation Trust (AGM, CM-B), Newcastle Upon Tyne, United Kingdom; Department of Rehabilitation and Regenerative Medicine (JM), Columbia University Irving Medical Center, New York; Neurorehabilitation Unit (VAS, EA), University of Milan, Neuromuscular Omnicentre Clinical Center, Niguarda Hospital; Unit of Neuromuscular and Neurodegenerative Disorders (ADA, ESB), Bambino Gesù Children's Hospital IRCCS, Rome; Center of Experimental and Translational Myology (CB), IRCCS Istituto Giannina Gaslini, Genoa and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa; Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud (SSM), University of Messina, Italy; Leeds Children Hospital (A-MC); The Robert Jones and Agnes Hunt Orthopaedic Hospital (TW), Oswestry; Sheffield Children's Hospital (MTO, LS); MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre (LS), University of Oxford, United Kingdom; Neuromuscular Reference Center, Department of Paediatrics, University and University Hospital of Liege, Belgium; Royal Hospital for Children (AM), Bristol; Royal Manchester Children's Hospital (IH); University Hospitals Birmingham (DP), United Kingdom; Evelina London Children's Hospital (VLG), London, UK; Departments of Neurology and Pediatrics (DCDV), Columbia University Irving Medical Center, New York; Department of Neurology (BTD), Boston Children's Hospital, Harvard Medical School, Boston, MA; Department of Neurology (JWD), Stanford University, Palo Alto, CA; Department of Paediatrics The Children's Hospital of Philadelphia (OM, ZZ-C), Philadelphia, PA; Nemours Children's Hospital (RSF), University of Central Florida College of Medicine, Orlando; St. Jude Children's Research Hospital (RSF), Memphis, TN; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), London, United Kingdom., Messina SS; Dubowitz Neuromuscular Centre (FT, HW, MS, AR, MLM, GB, FM), UCL Institute of Child Health & Great Ormond Street Hospital, London; Department Paediatric Neuroscience Evelina London Children's Hospital and Department Paediatric Respiratory Medicine (FT), Royal Brompton Hospital, Guy's and St Thomas NHS Trust London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (FT), IRCCS Istituto Giannina Gaslini, Genova and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Italy; Population (DR), Policy and Practice Programme, UCL GOS Institute of Child Health, London; Paediatric Neurology (GC, RDS, MP, MCP, EM), Università Cattolica del Sacro Cuore; Centro Clinico Nemo (GC, RDS, MP, MCP, EM), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Newcastle University and Newcastle Hospitals NHS Foundation Trust (AGM, CM-B), Newcastle Upon Tyne, United Kingdom; Department of Rehabilitation and Regenerative Medicine (JM), Columbia University Irving Medical Center, New York; Neurorehabilitation Unit (VAS, EA), University of Milan, Neuromuscular Omnicentre Clinical Center, Niguarda Hospital; Unit of Neuromuscular and Neurodegenerative Disorders (ADA, ESB), Bambino Gesù Children's Hospital IRCCS, Rome; Center of Experimental and Translational Myology (CB), IRCCS Istituto Giannina Gaslini, Genoa and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa; Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud (SSM), University of Messina, Italy; Leeds Children Hospital (A-MC); The Robert Jones and Agnes Hunt Orthopaedic Hospital (TW), Oswestry; Sheffield Children's Hospital (MTO, LS); MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre (LS), University of Oxford, United Kingdom; Neuromuscular Reference Center, Department of Paediatrics, University and University Hospital of Liege, Belgium; Royal Hospital for Children (AM), Bristol; Royal Manchester Children's Hospital (IH); University Hospitals Birmingham (DP), United Kingdom; Evelina London Children's Hospital (VLG), London, UK; Departments of Neurology and Pediatrics (DCDV), Columbia University Irving Medical Center, New York; Department of Neurology (BTD), Boston Children's Hospital, Harvard Medical School, Boston, MA; Department of Neurology (JWD), Stanford University, Palo Alto, CA; Department of Paediatrics The Children's Hospital of Philadelphia (OM, ZZ-C), Philadelphia, PA; Nemours Children's Hospital (RSF), University of Central Florida College of Medicine, Orlando; St. Jude Children's Research Hospital (RSF), Memphis, TN; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), London, United Kingdom., Childs AM; Dubowitz Neuromuscular Centre (FT, HW, MS, AR, MLM, GB, FM), UCL Institute of Child Health & Great Ormond Street Hospital, London; Department Paediatric Neuroscience Evelina London Children's Hospital and Department Paediatric Respiratory Medicine (FT), Royal Brompton Hospital, Guy's and St Thomas NHS Trust London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (FT), IRCCS Istituto Giannina Gaslini, Genova and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Italy; Population (DR), Policy and Practice Programme, UCL GOS Institute of Child Health, London; Paediatric Neurology (GC, RDS, MP, MCP, EM), Università Cattolica del Sacro Cuore; Centro Clinico Nemo (GC, RDS, MP, MCP, EM), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Newcastle University and Newcastle Hospitals NHS Foundation Trust (AGM, CM-B), Newcastle Upon Tyne, United Kingdom; Department of Rehabilitation and Regenerative Medicine (JM), Columbia University Irving Medical Center, New York; Neurorehabilitation Unit (VAS, EA), University of Milan, Neuromuscular Omnicentre Clinical Center, Niguarda Hospital; Unit of Neuromuscular and Neurodegenerative Disorders (ADA, ESB), Bambino Gesù Children's Hospital IRCCS, Rome; Center of Experimental and Translational Myology (CB), IRCCS Istituto Giannina Gaslini, Genoa and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa; Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud (SSM), University of Messina, Italy; Leeds Children Hospital (A-MC); The Robert Jones and Agnes Hunt Orthopaedic Hospital (TW), Oswestry; Sheffield Children's Hospital (MTO, LS); MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre (LS), University of Oxford, United Kingdom; Neuromuscular Reference Center, Department of Paediatrics, University and University Hospital of Liege, Belgium; Royal Hospital for Children (AM), Bristol; Royal Manchester Children's Hospital (IH); University Hospitals Birmingham (DP), United Kingdom; Evelina London Children's Hospital (VLG), London, UK; Departments of Neurology and Pediatrics (DCDV), Columbia University Irving Medical Center, New York; Department of Neurology (BTD), Boston Children's Hospital, Harvard Medical School, Boston, MA; Department of Neurology (JWD), Stanford University, Palo Alto, CA; Department of Paediatrics The Children's Hospital of Philadelphia (OM, ZZ-C), Philadelphia, PA; Nemours Children's Hospital (RSF), University of Central Florida College of Medicine, Orlando; St. Jude Children's Research Hospital (RSF), Memphis, TN; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), London, United Kingdom., Willis T; Dubowitz Neuromuscular Centre (FT, HW, MS, AR, MLM, GB, FM), UCL Institute of Child Health & Great Ormond Street Hospital, London; Department Paediatric Neuroscience Evelina London Children's Hospital and Department Paediatric Respiratory Medicine (FT), Royal Brompton Hospital, Guy's and St Thomas NHS Trust London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (FT), IRCCS Istituto Giannina Gaslini, Genova and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Italy; Population (DR), Policy and Practice Programme, UCL GOS Institute of Child Health, London; Paediatric Neurology (GC, RDS, MP, MCP, EM), Università Cattolica del Sacro Cuore; Centro Clinico Nemo (GC, RDS, MP, MCP, EM), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Newcastle University and Newcastle Hospitals NHS Foundation Trust (AGM, CM-B), Newcastle Upon Tyne, United Kingdom; Department of Rehabilitation and Regenerative Medicine (JM), Columbia University Irving Medical Center, New York; Neurorehabilitation Unit (VAS, EA), University of Milan, Neuromuscular Omnicentre Clinical Center, Niguarda Hospital; Unit of Neuromuscular and Neurodegenerative Disorders (ADA, ESB), Bambino Gesù Children's Hospital IRCCS, Rome; Center of Experimental and Translational Myology (CB), IRCCS Istituto Giannina Gaslini, Genoa and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa; Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud (SSM), University of Messina, Italy; Leeds Children Hospital (A-MC); The Robert Jones and Agnes Hunt Orthopaedic Hospital (TW), Oswestry; Sheffield Children's Hospital (MTO, LS); MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre (LS), University of Oxford, United Kingdom; Neuromuscular Reference Center, Department of Paediatrics, University and University Hospital of Liege, Belgium; Royal Hospital for Children (AM), Bristol; Royal Manchester Children's Hospital (IH); University Hospitals Birmingham (DP), United Kingdom; Evelina London Children's Hospital (VLG), London, UK; Departments of Neurology and Pediatrics (DCDV), Columbia University Irving Medical Center, New York; Department of Neurology (BTD), Boston Children's Hospital, Harvard Medical School, Boston, MA; Department of Neurology (JWD), Stanford University, Palo Alto, CA; Department of Paediatrics The Children's Hospital of Philadelphia (OM, ZZ-C), Philadelphia, PA; Nemours Children's Hospital (RSF), University of Central Florida College of Medicine, Orlando; St. Jude Children's Research Hospital (RSF), Memphis, TN; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), London, United Kingdom., Ong MT; Dubowitz Neuromuscular Centre (FT, HW, MS, AR, MLM, GB, FM), UCL Institute of Child Health & Great Ormond Street Hospital, London; Department Paediatric Neuroscience Evelina London Children's Hospital and Department Paediatric Respiratory Medicine (FT), Royal Brompton Hospital, Guy's and St Thomas NHS Trust London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (FT), IRCCS Istituto Giannina Gaslini, Genova and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Italy; Population (DR), Policy and Practice Programme, UCL GOS Institute of Child Health, London; Paediatric Neurology (GC, RDS, MP, MCP, EM), Università Cattolica del Sacro Cuore; Centro Clinico Nemo (GC, RDS, MP, MCP, EM), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Newcastle University and Newcastle Hospitals NHS Foundation Trust (AGM, CM-B), Newcastle Upon Tyne, United Kingdom; Department of Rehabilitation and Regenerative Medicine (JM), Columbia University Irving Medical Center, New York; Neurorehabilitation Unit (VAS, EA), University of Milan, Neuromuscular Omnicentre Clinical Center, Niguarda Hospital; Unit of Neuromuscular and Neurodegenerative Disorders (ADA, ESB), Bambino Gesù Children's Hospital IRCCS, Rome; Center of Experimental and Translational Myology (CB), IRCCS Istituto Giannina Gaslini, Genoa and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa; Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud (SSM), University of Messina, Italy; Leeds Children Hospital (A-MC); The Robert Jones and Agnes Hunt Orthopaedic Hospital (TW), Oswestry; Sheffield Children's Hospital (MTO, LS); MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre (LS), University of Oxford, United Kingdom; Neuromuscular Reference Center, Department of Paediatrics, University and University Hospital of Liege, Belgium; Royal Hospital for Children (AM), Bristol; Royal Manchester Children's Hospital (IH); University Hospitals Birmingham (DP), United Kingdom; Evelina London Children's Hospital (VLG), London, UK; Departments of Neurology and Pediatrics (DCDV), Columbia University Irving Medical Center, New York; Department of Neurology (BTD), Boston Children's Hospital, Harvard Medical School, Boston, MA; Department of Neurology (JWD), Stanford University, Palo Alto, CA; Department of Paediatrics The Children's Hospital of Philadelphia (OM, ZZ-C), Philadelphia, PA; Nemours Children's Hospital (RSF), University of Central Florida College of Medicine, Orlando; St. Jude Children's Research Hospital (RSF), Memphis, TN; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), London, United Kingdom., Servais L; Dubowitz Neuromuscular Centre (FT, HW, MS, AR, MLM, GB, FM), UCL Institute of Child Health & Great Ormond Street Hospital, London; Department Paediatric Neuroscience Evelina London Children's Hospital and Department Paediatric Respiratory Medicine (FT), Royal Brompton Hospital, Guy's and St Thomas NHS Trust London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (FT), IRCCS Istituto Giannina Gaslini, Genova and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Italy; Population (DR), Policy and Practice Programme, UCL GOS Institute of Child Health, London; Paediatric Neurology (GC, RDS, MP, MCP, EM), Università Cattolica del Sacro Cuore; Centro Clinico Nemo (GC, RDS, MP, MCP, EM), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Newcastle University and Newcastle Hospitals NHS Foundation Trust (AGM, CM-B), Newcastle Upon Tyne, United Kingdom; Department of Rehabilitation and Regenerative Medicine (JM), Columbia University Irving Medical Center, New York; Neurorehabilitation Unit (VAS, EA), University of Milan, Neuromuscular Omnicentre Clinical Center, Niguarda Hospital; Unit of Neuromuscular and Neurodegenerative Disorders (ADA, ESB), Bambino Gesù Children's Hospital IRCCS, Rome; Center of Experimental and Translational Myology (CB), IRCCS Istituto Giannina Gaslini, Genoa and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa; Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud (SSM), University of Messina, Italy; Leeds Children Hospital (A-MC); The Robert Jones and Agnes Hunt Orthopaedic Hospital (TW), Oswestry; Sheffield Children's Hospital (MTO, LS); MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre (LS), University of Oxford, United Kingdom; Neuromuscular Reference Center, Department of Paediatrics, University and University Hospital of Liege, Belgium; Royal Hospital for Children (AM), Bristol; Royal Manchester Children's Hospital (IH); University Hospitals Birmingham (DP), United Kingdom; Evelina London Children's Hospital (VLG), London, UK; Departments of Neurology and Pediatrics (DCDV), Columbia University Irving Medical Center, New York; Department of Neurology (BTD), Boston Children's Hospital, Harvard Medical School, Boston, MA; Department of Neurology (JWD), Stanford University, Palo Alto, CA; Department of Paediatrics The Children's Hospital of Philadelphia (OM, ZZ-C), Philadelphia, PA; Nemours Children's Hospital (RSF), University of Central Florida College of Medicine, Orlando; St. Jude Children's Research Hospital (RSF), Memphis, TN; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), London, United Kingdom., Majumdar A; Dubowitz Neuromuscular Centre (FT, HW, MS, AR, MLM, GB, FM), UCL Institute of Child Health & Great Ormond Street Hospital, London; Department Paediatric Neuroscience Evelina London Children's Hospital and Department Paediatric Respiratory Medicine (FT), Royal Brompton Hospital, Guy's and St Thomas NHS Trust London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (FT), IRCCS Istituto Giannina Gaslini, Genova and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Italy; Population (DR), Policy and Practice Programme, UCL GOS Institute of Child Health, London; Paediatric Neurology (GC, RDS, MP, MCP, EM), Università Cattolica del Sacro Cuore; Centro Clinico Nemo (GC, RDS, MP, MCP, EM), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Newcastle University and Newcastle Hospitals NHS Foundation Trust (AGM, CM-B), Newcastle Upon Tyne, United Kingdom; Department of Rehabilitation and Regenerative Medicine (JM), Columbia University Irving Medical Center, New York; Neurorehabilitation Unit (VAS, EA), University of Milan, Neuromuscular Omnicentre Clinical Center, Niguarda Hospital; Unit of Neuromuscular and Neurodegenerative Disorders (ADA, ESB), Bambino Gesù Children's Hospital IRCCS, Rome; Center of Experimental and Translational Myology (CB), IRCCS Istituto Giannina Gaslini, Genoa and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa; Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud (SSM), University of Messina, Italy; Leeds Children Hospital (A-MC); The Robert Jones and Agnes Hunt Orthopaedic Hospital (TW), Oswestry; Sheffield Children's Hospital (MTO, LS); MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre (LS), University of Oxford, United Kingdom; Neuromuscular Reference Center, Department of Paediatrics, University and University Hospital of Liege, Belgium; Royal Hospital for Children (AM), Bristol; Royal Manchester Children's Hospital (IH); University Hospitals Birmingham (DP), United Kingdom; Evelina London Children's Hospital (VLG), London, UK; Departments of Neurology and Pediatrics (DCDV), Columbia University Irving Medical Center, New York; Department of Neurology (BTD), Boston Children's Hospital, Harvard Medical School, Boston, MA; Department of Neurology (JWD), Stanford University, Palo Alto, CA; Department of Paediatrics The Children's Hospital of Philadelphia (OM, ZZ-C), Philadelphia, PA; Nemours Children's Hospital (RSF), University of Central Florida College of Medicine, Orlando; St. Jude Children's Research Hospital (RSF), Memphis, TN; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), London, United Kingdom., Hughes I; Dubowitz Neuromuscular Centre (FT, HW, MS, AR, MLM, GB, FM), UCL Institute of Child Health & Great Ormond Street Hospital, London; Department Paediatric Neuroscience Evelina London Children's Hospital and Department Paediatric Respiratory Medicine (FT), Royal Brompton Hospital, Guy's and St Thomas NHS Trust London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (FT), IRCCS Istituto Giannina Gaslini, Genova and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Italy; Population (DR), Policy and Practice Programme, UCL GOS Institute of Child Health, London; Paediatric Neurology (GC, RDS, MP, MCP, EM), Università Cattolica del Sacro Cuore; Centro Clinico Nemo (GC, RDS, MP, MCP, EM), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Newcastle University and Newcastle Hospitals NHS Foundation Trust (AGM, CM-B), Newcastle Upon Tyne, United Kingdom; Department of Rehabilitation and Regenerative Medicine (JM), Columbia University Irving Medical Center, New York; Neurorehabilitation Unit (VAS, EA), University of Milan, Neuromuscular Omnicentre Clinical Center, Niguarda Hospital; Unit of Neuromuscular and Neurodegenerative Disorders (ADA, ESB), Bambino Gesù Children's Hospital IRCCS, Rome; Center of Experimental and Translational Myology (CB), IRCCS Istituto Giannina Gaslini, Genoa and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa; Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud (SSM), University of Messina, Italy; Leeds Children Hospital (A-MC); The Robert Jones and Agnes Hunt Orthopaedic Hospital (TW), Oswestry; Sheffield Children's Hospital (MTO, LS); MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre (LS), University of Oxford, United Kingdom; Neuromuscular Reference Center, Department of Paediatrics, University and University Hospital of Liege, Belgium; Royal Hospital for Children (AM), Bristol; Royal Manchester Children's Hospital (IH); University Hospitals Birmingham (DP), United Kingdom; Evelina London Children's Hospital (VLG), London, UK; Departments of Neurology and Pediatrics (DCDV), Columbia University Irving Medical Center, New York; Department of Neurology (BTD), Boston Children's Hospital, Harvard Medical School, Boston, MA; Department of Neurology (JWD), Stanford University, Palo Alto, CA; Department of Paediatrics The Children's Hospital of Philadelphia (OM, ZZ-C), Philadelphia, PA; Nemours Children's Hospital (RSF), University of Central Florida College of Medicine, Orlando; St. Jude Children's Research Hospital (RSF), Memphis, TN; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), London, United Kingdom., Marini-Bettolo C; Dubowitz Neuromuscular Centre (FT, HW, MS, AR, MLM, GB, FM), UCL Institute of Child Health & Great Ormond Street Hospital, London; Department Paediatric Neuroscience Evelina London Children's Hospital and Department Paediatric Respiratory Medicine (FT), Royal Brompton Hospital, Guy's and St Thomas NHS Trust London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (FT), IRCCS Istituto Giannina Gaslini, Genova and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Italy; Population (DR), Policy and Practice Programme, UCL GOS Institute of Child Health, London; Paediatric Neurology (GC, RDS, MP, MCP, EM), Università Cattolica del Sacro Cuore; Centro Clinico Nemo (GC, RDS, MP, MCP, EM), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Newcastle University and Newcastle Hospitals NHS Foundation Trust (AGM, CM-B), Newcastle Upon Tyne, United Kingdom; Department of Rehabilitation and Regenerative Medicine (JM), Columbia University Irving Medical Center, New York; Neurorehabilitation Unit (VAS, EA), University of Milan, Neuromuscular Omnicentre Clinical Center, Niguarda Hospital; Unit of Neuromuscular and Neurodegenerative Disorders (ADA, ESB), Bambino Gesù Children's Hospital IRCCS, Rome; Center of Experimental and Translational Myology (CB), IRCCS Istituto Giannina Gaslini, Genoa and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa; Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud (SSM), University of Messina, Italy; Leeds Children Hospital (A-MC); The Robert Jones and Agnes Hunt Orthopaedic Hospital (TW), Oswestry; Sheffield Children's Hospital (MTO, LS); MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre (LS), University of Oxford, United Kingdom; Neuromuscular Reference Center, Department of Paediatrics, University and University Hospital of Liege, Belgium; Royal Hospital for Children (AM), Bristol; Royal Manchester Children's Hospital (IH); University Hospitals Birmingham (DP), United Kingdom; Evelina London Children's Hospital (VLG), London, UK; Departments of Neurology and Pediatrics (DCDV), Columbia University Irving Medical Center, New York; Department of Neurology (BTD), Boston Children's Hospital, Harvard Medical School, Boston, MA; Department of Neurology (JWD), Stanford University, Palo Alto, CA; Department of Paediatrics The Children's Hospital of Philadelphia (OM, ZZ-C), Philadelphia, PA; Nemours Children's Hospital (RSF), University of Central Florida College of Medicine, Orlando; St. Jude Children's Research Hospital (RSF), Memphis, TN; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), London, United Kingdom., Parasuraman D; Dubowitz Neuromuscular Centre (FT, HW, MS, AR, MLM, GB, FM), UCL Institute of Child Health & Great Ormond Street Hospital, London; Department Paediatric Neuroscience Evelina London Children's Hospital and Department Paediatric Respiratory Medicine (FT), Royal Brompton Hospital, Guy's and St Thomas NHS Trust London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (FT), IRCCS Istituto Giannina Gaslini, Genova and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Italy; Population (DR), Policy and Practice Programme, UCL GOS Institute of Child Health, London; Paediatric Neurology (GC, RDS, MP, MCP, EM), Università Cattolica del Sacro Cuore; Centro Clinico Nemo (GC, RDS, MP, MCP, EM), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Newcastle University and Newcastle Hospitals NHS Foundation Trust (AGM, CM-B), Newcastle Upon Tyne, United Kingdom; Department of Rehabilitation and Regenerative Medicine (JM), Columbia University Irving Medical Center, New York; Neurorehabilitation Unit (VAS, EA), University of Milan, Neuromuscular Omnicentre Clinical Center, Niguarda Hospital; Unit of Neuromuscular and Neurodegenerative Disorders (ADA, ESB), Bambino Gesù Children's Hospital IRCCS, Rome; Center of Experimental and Translational Myology (CB), IRCCS Istituto Giannina Gaslini, Genoa and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa; Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud (SSM), University of Messina, Italy; Leeds Children Hospital (A-MC); The Robert Jones and Agnes Hunt Orthopaedic Hospital (TW), Oswestry; Sheffield Children's Hospital (MTO, LS); MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre (LS), University of Oxford, United Kingdom; Neuromuscular Reference Center, Department of Paediatrics, University and University Hospital of Liege, Belgium; Royal Hospital for Children (AM), Bristol; Royal Manchester Children's Hospital (IH); University Hospitals Birmingham (DP), United Kingdom; Evelina London Children's Hospital (VLG), London, UK; Departments of Neurology and Pediatrics (DCDV), Columbia University Irving Medical Center, New York; Department of Neurology (BTD), Boston Children's Hospital, Harvard Medical School, Boston, MA; Department of Neurology (JWD), Stanford University, Palo Alto, CA; Department of Paediatrics The Children's Hospital of Philadelphia (OM, ZZ-C), Philadelphia, PA; Nemours Children's Hospital (RSF), University of Central Florida College of Medicine, Orlando; St. Jude Children's Research Hospital (RSF), Memphis, TN; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), London, United Kingdom., Gowda VL; Dubowitz Neuromuscular Centre (FT, HW, MS, AR, MLM, GB, FM), UCL Institute of Child Health & Great Ormond Street Hospital, London; Department Paediatric Neuroscience Evelina London Children's Hospital and Department Paediatric Respiratory Medicine (FT), Royal Brompton Hospital, Guy's and St Thomas NHS Trust London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (FT), IRCCS Istituto Giannina Gaslini, Genova and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Italy; Population (DR), Policy and Practice Programme, UCL GOS Institute of Child Health, London; Paediatric Neurology (GC, RDS, MP, MCP, EM), Università Cattolica del Sacro Cuore; Centro Clinico Nemo (GC, RDS, MP, MCP, EM), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Newcastle University and Newcastle Hospitals NHS Foundation Trust (AGM, CM-B), Newcastle Upon Tyne, United Kingdom; Department of Rehabilitation and Regenerative Medicine (JM), Columbia University Irving Medical Center, New York; Neurorehabilitation Unit (VAS, EA), University of Milan, Neuromuscular Omnicentre Clinical Center, Niguarda Hospital; Unit of Neuromuscular and Neurodegenerative Disorders (ADA, ESB), Bambino Gesù Children's Hospital IRCCS, Rome; Center of Experimental and Translational Myology (CB), IRCCS Istituto Giannina Gaslini, Genoa and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa; Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud (SSM), University of Messina, Italy; Leeds Children Hospital (A-MC); The Robert Jones and Agnes Hunt Orthopaedic Hospital (TW), Oswestry; Sheffield Children's Hospital (MTO, LS); MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre (LS), University of Oxford, United Kingdom; Neuromuscular Reference Center, Department of Paediatrics, University and University Hospital of Liege, Belgium; Royal Hospital for Children (AM), Bristol; Royal Manchester Children's Hospital (IH); University Hospitals Birmingham (DP), United Kingdom; Evelina London Children's Hospital (VLG), London, UK; Departments of Neurology and Pediatrics (DCDV), Columbia University Irving Medical Center, New York; Department of Neurology (BTD), Boston Children's Hospital, Harvard Medical School, Boston, MA; Department of Neurology (JWD), Stanford University, Palo Alto, CA; Department of Paediatrics The Children's Hospital of Philadelphia (OM, ZZ-C), Philadelphia, PA; Nemours Children's Hospital (RSF), University of Central Florida College of Medicine, Orlando; St. Jude Children's Research Hospital (RSF), Memphis, TN; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), London, United Kingdom., Baranello G; Dubowitz Neuromuscular Centre (FT, HW, MS, AR, MLM, GB, FM), UCL Institute of Child Health & Great Ormond Street Hospital, London; Department Paediatric Neuroscience Evelina London Children's Hospital and Department Paediatric Respiratory Medicine (FT), Royal Brompton Hospital, Guy's and St Thomas NHS Trust London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (FT), IRCCS Istituto Giannina Gaslini, Genova and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Italy; Population (DR), Policy and Practice Programme, UCL GOS Institute of Child Health, London; Paediatric Neurology (GC, RDS, MP, MCP, EM), Università Cattolica del Sacro Cuore; Centro Clinico Nemo (GC, RDS, MP, MCP, EM), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Newcastle University and Newcastle Hospitals NHS Foundation Trust (AGM, CM-B), Newcastle Upon Tyne, United Kingdom; Department of Rehabilitation and Regenerative Medicine (JM), Columbia University Irving Medical Center, New York; Neurorehabilitation Unit (VAS, EA), University of Milan, Neuromuscular Omnicentre Clinical Center, Niguarda Hospital; Unit of Neuromuscular and Neurodegenerative Disorders (ADA, ESB), Bambino Gesù Children's Hospital IRCCS, Rome; Center of Experimental and Translational Myology (CB), IRCCS Istituto Giannina Gaslini, Genoa and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa; Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud (SSM), University of Messina, Italy; Leeds Children Hospital (A-MC); The Robert Jones and Agnes Hunt Orthopaedic Hospital (TW), Oswestry; Sheffield Children's Hospital (MTO, LS); MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre (LS), University of Oxford, United Kingdom; Neuromuscular Reference Center, Department of Paediatrics, University and University Hospital of Liege, Belgium; Royal Hospital for Children (AM), Bristol; Royal Manchester Children's Hospital (IH); University Hospitals Birmingham (DP), United Kingdom; Evelina London Children's Hospital (VLG), London, UK; Departments of Neurology and Pediatrics (DCDV), Columbia University Irving Medical Center, New York; Department of Neurology (BTD), Boston Children's Hospital, Harvard Medical School, Boston, MA; Department of Neurology (JWD), Stanford University, Palo Alto, CA; Department of Paediatrics The Children's Hospital of Philadelphia (OM, ZZ-C), Philadelphia, PA; Nemours Children's Hospital (RSF), University of Central Florida College of Medicine, Orlando; St. Jude Children's Research Hospital (RSF), Memphis, TN; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), London, United Kingdom., Bertini ES; Dubowitz Neuromuscular Centre (FT, HW, MS, AR, MLM, GB, FM), UCL Institute of Child Health & Great Ormond Street Hospital, London; Department Paediatric Neuroscience Evelina London Children's Hospital and Department Paediatric Respiratory Medicine (FT), Royal Brompton Hospital, Guy's and St Thomas NHS Trust London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (FT), IRCCS Istituto Giannina Gaslini, Genova and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Italy; Population (DR), Policy and Practice Programme, UCL GOS Institute of Child Health, London; Paediatric Neurology (GC, RDS, MP, MCP, EM), Università Cattolica del Sacro Cuore; Centro Clinico Nemo (GC, RDS, MP, MCP, EM), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Newcastle University and Newcastle Hospitals NHS Foundation Trust (AGM, CM-B), Newcastle Upon Tyne, United Kingdom; Department of Rehabilitation and Regenerative Medicine (JM), Columbia University Irving Medical Center, New York; Neurorehabilitation Unit (VAS, EA), University of Milan, Neuromuscular Omnicentre Clinical Center, Niguarda Hospital; Unit of Neuromuscular and Neurodegenerative Disorders (ADA, ESB), Bambino Gesù Children's Hospital IRCCS, Rome; Center of Experimental and Translational Myology (CB), IRCCS Istituto Giannina Gaslini, Genoa and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa; Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud (SSM), University of Messina, Italy; Leeds Children Hospital (A-MC); The Robert Jones and Agnes Hunt Orthopaedic Hospital (TW), Oswestry; Sheffield Children's Hospital (MTO, LS); MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre (LS), University of Oxford, United Kingdom; Neuromuscular Reference Center, Department of Paediatrics, University and University Hospital of Liege, Belgium; Royal Hospital for Children (AM), Bristol; Royal Manchester Children's Hospital (IH); University Hospitals Birmingham (DP), United Kingdom; Evelina London Children's Hospital (VLG), London, UK; Departments of Neurology and Pediatrics (DCDV), Columbia University Irving Medical Center, New York; Department of Neurology (BTD), Boston Children's Hospital, Harvard Medical School, Boston, MA; Department of Neurology (JWD), Stanford University, Palo Alto, CA; Department of Paediatrics The Children's Hospital of Philadelphia (OM, ZZ-C), Philadelphia, PA; Nemours Children's Hospital (RSF), University of Central Florida College of Medicine, Orlando; St. Jude Children's Research Hospital (RSF), Memphis, TN; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), London, United Kingdom., De Vivo DC; Dubowitz Neuromuscular Centre (FT, HW, MS, AR, MLM, GB, FM), UCL Institute of Child Health & Great Ormond Street Hospital, London; Department Paediatric Neuroscience Evelina London Children's Hospital and Department Paediatric Respiratory Medicine (FT), Royal Brompton Hospital, Guy's and St Thomas NHS Trust London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (FT), IRCCS Istituto Giannina Gaslini, Genova and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Italy; Population (DR), Policy and Practice Programme, UCL GOS Institute of Child Health, London; Paediatric Neurology (GC, RDS, MP, MCP, EM), Università Cattolica del Sacro Cuore; Centro Clinico Nemo (GC, RDS, MP, MCP, EM), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Newcastle University and Newcastle Hospitals NHS Foundation Trust (AGM, CM-B), Newcastle Upon Tyne, United Kingdom; Department of Rehabilitation and Regenerative Medicine (JM), Columbia University Irving Medical Center, New York; Neurorehabilitation Unit (VAS, EA), University of Milan, Neuromuscular Omnicentre Clinical Center, Niguarda Hospital; Unit of Neuromuscular and Neurodegenerative Disorders (ADA, ESB), Bambino Gesù Children's Hospital IRCCS, Rome; Center of Experimental and Translational Myology (CB), IRCCS Istituto Giannina Gaslini, Genoa and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa; Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud (SSM), University of Messina, Italy; Leeds Children Hospital (A-MC); The Robert Jones and Agnes Hunt Orthopaedic Hospital (TW), Oswestry; Sheffield Children's Hospital (MTO, LS); MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre (LS), University of Oxford, United Kingdom; Neuromuscular Reference Center, Department of Paediatrics, University and University Hospital of Liege, Belgium; Royal Hospital for Children (AM), Bristol; Royal Manchester Children's Hospital (IH); University Hospitals Birmingham (DP), United Kingdom; Evelina London Children's Hospital (VLG), London, UK; Departments of Neurology and Pediatrics (DCDV), Columbia University Irving Medical Center, New York; Department of Neurology (BTD), Boston Children's Hospital, Harvard Medical School, Boston, MA; Department of Neurology (JWD), Stanford University, Palo Alto, CA; Department of Paediatrics The Children's Hospital of Philadelphia (OM, ZZ-C), Philadelphia, PA; Nemours Children's Hospital (RSF), University of Central Florida College of Medicine, Orlando; St. Jude Children's Research Hospital (RSF), Memphis, TN; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), London, United Kingdom., Darras BT; Dubowitz Neuromuscular Centre (FT, HW, MS, AR, MLM, GB, FM), UCL Institute of Child Health & Great Ormond Street Hospital, London; Department Paediatric Neuroscience Evelina London Children's Hospital and Department Paediatric Respiratory Medicine (FT), Royal Brompton Hospital, Guy's and St Thomas NHS Trust London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (FT), IRCCS Istituto Giannina Gaslini, Genova and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Italy; Population (DR), Policy and Practice Programme, UCL GOS Institute of Child Health, London; Paediatric Neurology (GC, RDS, MP, MCP, EM), Università Cattolica del Sacro Cuore; Centro Clinico Nemo (GC, RDS, MP, MCP, EM), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Newcastle University and Newcastle Hospitals NHS Foundation Trust (AGM, CM-B), Newcastle Upon Tyne, United Kingdom; Department of Rehabilitation and Regenerative Medicine (JM), Columbia University Irving Medical Center, New York; Neurorehabilitation Unit (VAS, EA), University of Milan, Neuromuscular Omnicentre Clinical Center, Niguarda Hospital; Unit of Neuromuscular and Neurodegenerative Disorders (ADA, ESB), Bambino Gesù Children's Hospital IRCCS, Rome; Center of Experimental and Translational Myology (CB), IRCCS Istituto Giannina Gaslini, Genoa and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa; Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud (SSM), University of Messina, Italy; Leeds Children Hospital (A-MC); The Robert Jones and Agnes Hunt Orthopaedic Hospital (TW), Oswestry; Sheffield Children's Hospital (MTO, LS); MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre (LS), University of Oxford, United Kingdom; Neuromuscular Reference Center, Department of Paediatrics, University and University Hospital of Liege, Belgium; Royal Hospital for Children (AM), Bristol; Royal Manchester Children's Hospital (IH); University Hospitals Birmingham (DP), United Kingdom; Evelina London Children's Hospital (VLG), London, UK; Departments of Neurology and Pediatrics (DCDV), Columbia University Irving Medical Center, New York; Department of Neurology (BTD), Boston Children's Hospital, Harvard Medical School, Boston, MA; Department of Neurology (JWD), Stanford University, Palo Alto, CA; Department of Paediatrics The Children's Hospital of Philadelphia (OM, ZZ-C), Philadelphia, PA; Nemours Children's Hospital (RSF), University of Central Florida College of Medicine, Orlando; St. Jude Children's Research Hospital (RSF), Memphis, TN; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), London, United Kingdom., Day JW; Dubowitz Neuromuscular Centre (FT, HW, MS, AR, MLM, GB, FM), UCL Institute of Child Health & Great Ormond Street Hospital, London; Department Paediatric Neuroscience Evelina London Children's Hospital and Department Paediatric Respiratory Medicine (FT), Royal Brompton Hospital, Guy's and St Thomas NHS Trust London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (FT), IRCCS Istituto Giannina Gaslini, Genova and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Italy; Population (DR), Policy and Practice Programme, UCL GOS Institute of Child Health, London; Paediatric Neurology (GC, RDS, MP, MCP, EM), Università Cattolica del Sacro Cuore; Centro Clinico Nemo (GC, RDS, MP, MCP, EM), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Newcastle University and Newcastle Hospitals NHS Foundation Trust (AGM, CM-B), Newcastle Upon Tyne, United Kingdom; Department of Rehabilitation and Regenerative Medicine (JM), Columbia University Irving Medical Center, New York; Neurorehabilitation Unit (VAS, EA), University of Milan, Neuromuscular Omnicentre Clinical Center, Niguarda Hospital; Unit of Neuromuscular and Neurodegenerative Disorders (ADA, ESB), Bambino Gesù Children's Hospital IRCCS, Rome; Center of Experimental and Translational Myology (CB), IRCCS Istituto Giannina Gaslini, Genoa and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa; Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud (SSM), University of Messina, Italy; Leeds Children Hospital (A-MC); The Robert Jones and Agnes Hunt Orthopaedic Hospital (TW), Oswestry; Sheffield Children's Hospital (MTO, LS); MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre (LS), University of Oxford, United Kingdom; Neuromuscular Reference Center, Department of Paediatrics, University and University Hospital of Liege, Belgium; Royal Hospital for Children (AM), Bristol; Royal Manchester Children's Hospital (IH); University Hospitals Birmingham (DP), United Kingdom; Evelina London Children's Hospital (VLG), London, UK; Departments of Neurology and Pediatrics (DCDV), Columbia University Irving Medical Center, New York; Department of Neurology (BTD), Boston Children's Hospital, Harvard Medical School, Boston, MA; Department of Neurology (JWD), Stanford University, Palo Alto, CA; Department of Paediatrics The Children's Hospital of Philadelphia (OM, ZZ-C), Philadelphia, PA; Nemours Children's Hospital (RSF), University of Central Florida College of Medicine, Orlando; St. Jude Children's Research Hospital (RSF), Memphis, TN; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), London, United Kingdom., Mayer O; Dubowitz Neuromuscular Centre (FT, HW, MS, AR, MLM, GB, FM), UCL Institute of Child Health & Great Ormond Street Hospital, London; Department Paediatric Neuroscience Evelina London Children's Hospital and Department Paediatric Respiratory Medicine (FT), Royal Brompton Hospital, Guy's and St Thomas NHS Trust London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (FT), IRCCS Istituto Giannina Gaslini, Genova and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Italy; Population (DR), Policy and Practice Programme, UCL GOS Institute of Child Health, London; Paediatric Neurology (GC, RDS, MP, MCP, EM), Università Cattolica del Sacro Cuore; Centro Clinico Nemo (GC, RDS, MP, MCP, EM), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Newcastle University and Newcastle Hospitals NHS Foundation Trust (AGM, CM-B), Newcastle Upon Tyne, United Kingdom; Department of Rehabilitation and Regenerative Medicine (JM), Columbia University Irving Medical Center, New York; Neurorehabilitation Unit (VAS, EA), University of Milan, Neuromuscular Omnicentre Clinical Center, Niguarda Hospital; Unit of Neuromuscular and Neurodegenerative Disorders (ADA, ESB), Bambino Gesù Children's Hospital IRCCS, Rome; Center of Experimental and Translational Myology (CB), IRCCS Istituto Giannina Gaslini, Genoa and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa; Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud (SSM), University of Messina, Italy; Leeds Children Hospital (A-MC); The Robert Jones and Agnes Hunt Orthopaedic Hospital (TW), Oswestry; Sheffield Children's Hospital (MTO, LS); MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre (LS), University of Oxford, United Kingdom; Neuromuscular Reference Center, Department of Paediatrics, University and University Hospital of Liege, Belgium; Royal Hospital for Children (AM), Bristol; Royal Manchester Children's Hospital (IH); University Hospitals Birmingham (DP), United Kingdom; Evelina London Children's Hospital (VLG), London, UK; Departments of Neurology and Pediatrics (DCDV), Columbia University Irving Medical Center, New York; Department of Neurology (BTD), Boston Children's Hospital, Harvard Medical School, Boston, MA; Department of Neurology (JWD), Stanford University, Palo Alto, CA; Department of Paediatrics The Children's Hospital of Philadelphia (OM, ZZ-C), Philadelphia, PA; Nemours Children's Hospital (RSF), University of Central Florida College of Medicine, Orlando; St. Jude Children's Research Hospital (RSF), Memphis, TN; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), London, United Kingdom., Zolkipli-Cunningham Z; Dubowitz Neuromuscular Centre (FT, HW, MS, AR, MLM, GB, FM), UCL Institute of Child Health & Great Ormond Street Hospital, London; Department Paediatric Neuroscience Evelina London Children's Hospital and Department Paediatric Respiratory Medicine (FT), Royal Brompton Hospital, Guy's and St Thomas NHS Trust London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (FT), IRCCS Istituto Giannina Gaslini, Genova and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Italy; Population (DR), Policy and Practice Programme, UCL GOS Institute of Child Health, London; Paediatric Neurology (GC, RDS, MP, MCP, EM), Università Cattolica del Sacro Cuore; Centro Clinico Nemo (GC, RDS, MP, MCP, EM), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Newcastle University and Newcastle Hospitals NHS Foundation Trust (AGM, CM-B), Newcastle Upon Tyne, United Kingdom; Department of Rehabilitation and Regenerative Medicine (JM), Columbia University Irving Medical Center, New York; Neurorehabilitation Unit (VAS, EA), University of Milan, Neuromuscular Omnicentre Clinical Center, Niguarda Hospital; Unit of Neuromuscular and Neurodegenerative Disorders (ADA, ESB), Bambino Gesù Children's Hospital IRCCS, Rome; Center of Experimental and Translational Myology (CB), IRCCS Istituto Giannina Gaslini, Genoa and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa; Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud (SSM), University of Messina, Italy; Leeds Children Hospital (A-MC); The Robert Jones and Agnes Hunt Orthopaedic Hospital (TW), Oswestry; Sheffield Children's Hospital (MTO, LS); MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre (LS), University of Oxford, United Kingdom; Neuromuscular Reference Center, Department of Paediatrics, University and University Hospital of Liege, Belgium; Royal Hospital for Children (AM), Bristol; Royal Manchester Children's Hospital (IH); University Hospitals Birmingham (DP), United Kingdom; Evelina London Children's Hospital (VLG), London, UK; Departments of Neurology and Pediatrics (DCDV), Columbia University Irving Medical Center, New York; Department of Neurology (BTD), Boston Children's Hospital, Harvard Medical School, Boston, MA; Department of Neurology (JWD), Stanford University, Palo Alto, CA; Department of Paediatrics The Children's Hospital of Philadelphia (OM, ZZ-C), Philadelphia, PA; Nemours Children's Hospital (RSF), University of Central Florida College of Medicine, Orlando; St. Jude Children's Research Hospital (RSF), Memphis, TN; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), London, United Kingdom., Finkel RS; Dubowitz Neuromuscular Centre (FT, HW, MS, AR, MLM, GB, FM), UCL Institute of Child Health & Great Ormond Street Hospital, London; Department Paediatric Neuroscience Evelina London Children's Hospital and Department Paediatric Respiratory Medicine (FT), Royal Brompton Hospital, Guy's and St Thomas NHS Trust London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (FT), IRCCS Istituto Giannina Gaslini, Genova and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Italy; Population (DR), Policy and Practice Programme, UCL GOS Institute of Child Health, London; Paediatric Neurology (GC, RDS, MP, MCP, EM), Università Cattolica del Sacro Cuore; Centro Clinico Nemo (GC, RDS, MP, MCP, EM), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Newcastle University and Newcastle Hospitals NHS Foundation Trust (AGM, CM-B), Newcastle Upon Tyne, United Kingdom; Department of Rehabilitation and Regenerative Medicine (JM), Columbia University Irving Medical Center, New York; Neurorehabilitation Unit (VAS, EA), University of Milan, Neuromuscular Omnicentre Clinical Center, Niguarda Hospital; Unit of Neuromuscular and Neurodegenerative Disorders (ADA, ESB), Bambino Gesù Children's Hospital IRCCS, Rome; Center of Experimental and Translational Myology (CB), IRCCS Istituto Giannina Gaslini, Genoa and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa; Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud (SSM), University of Messina, Italy; Leeds Children Hospital (A-MC); The Robert Jones and Agnes Hunt Orthopaedic Hospital (TW), Oswestry; Sheffield Children's Hospital (MTO, LS); MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre (LS), University of Oxford, United Kingdom; Neuromuscular Reference Center, Department of Paediatrics, University and University Hospital of Liege, Belgium; Royal Hospital for Children (AM), Bristol; Royal Manchester Children's Hospital (IH); University Hospitals Birmingham (DP), United Kingdom; Evelina London Children's Hospital (VLG), London, UK; Departments of Neurology and Pediatrics (DCDV), Columbia University Irving Medical Center, New York; Department of Neurology (BTD), Boston Children's Hospital, Harvard Medical School, Boston, MA; Department of Neurology (JWD), Stanford University, Palo Alto, CA; Department of Paediatrics The Children's Hospital of Philadelphia (OM, ZZ-C), Philadelphia, PA; Nemours Children's Hospital (RSF), University of Central Florida College of Medicine, Orlando; St. Jude Children's Research Hospital (RSF), Memphis, TN; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), London, United Kingdom., Mercuri E; Dubowitz Neuromuscular Centre (FT, HW, MS, AR, MLM, GB, FM), UCL Institute of Child Health & Great Ormond Street Hospital, London; Department Paediatric Neuroscience Evelina London Children's Hospital and Department Paediatric Respiratory Medicine (FT), Royal Brompton Hospital, Guy's and St Thomas NHS Trust London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (FT), IRCCS Istituto Giannina Gaslini, Genova and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Italy; Population (DR), Policy and Practice Programme, UCL GOS Institute of Child Health, London; Paediatric Neurology (GC, RDS, MP, MCP, EM), Università Cattolica del Sacro Cuore; Centro Clinico Nemo (GC, RDS, MP, MCP, EM), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Newcastle University and Newcastle Hospitals NHS Foundation Trust (AGM, CM-B), Newcastle Upon Tyne, United Kingdom; Department of Rehabilitation and Regenerative Medicine (JM), Columbia University Irving Medical Center, New York; Neurorehabilitation Unit (VAS, EA), University of Milan, Neuromuscular Omnicentre Clinical Center, Niguarda Hospital; Unit of Neuromuscular and Neurodegenerative Disorders (ADA, ESB), Bambino Gesù Children's Hospital IRCCS, Rome; Center of Experimental and Translational Myology (CB), IRCCS Istituto Giannina Gaslini, Genoa and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa; Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud (SSM), University of Messina, Italy; Leeds Children Hospital (A-MC); The Robert Jones and Agnes Hunt Orthopaedic Hospital (TW), Oswestry; Sheffield Children's Hospital (MTO, LS); MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre (LS), University of Oxford, United Kingdom; Neuromuscular Reference Center, Department of Paediatrics, University and University Hospital of Liege, Belgium; Royal Hospital for Children (AM), Bristol; Royal Manchester Children's Hospital (IH); University Hospitals Birmingham (DP), United Kingdom; Evelina London Children's Hospital (VLG), London, UK; Departments of Neurology and Pediatrics (DCDV), Columbia University Irving Medical Center, New York; Department of Neurology (BTD), Boston Children's Hospital, Harvard Medical School, Boston, MA; Department of Neurology (JWD), Stanford University, Palo Alto, CA; Department of Paediatrics The Children's Hospital of Philadelphia (OM, ZZ-C), Philadelphia, PA; Nemours Children's Hospital (RSF), University of Central Florida College of Medicine, Orlando; St. Jude Children's Research Hospital (RSF), Memphis, TN; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), London, United Kingdom., Muntoni F; Dubowitz Neuromuscular Centre (FT, HW, MS, AR, MLM, GB, FM), UCL Institute of Child Health & Great Ormond Street Hospital, London; Department Paediatric Neuroscience Evelina London Children's Hospital and Department Paediatric Respiratory Medicine (FT), Royal Brompton Hospital, Guy's and St Thomas NHS Trust London, United Kingdom; Pediatric Neurology and Muscular Diseases Unit (FT), IRCCS Istituto Giannina Gaslini, Genova and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Italy; Population (DR), Policy and Practice Programme, UCL GOS Institute of Child Health, London; Paediatric Neurology (GC, RDS, MP, MCP, EM), Università Cattolica del Sacro Cuore; Centro Clinico Nemo (GC, RDS, MP, MCP, EM), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy; Newcastle University and Newcastle Hospitals NHS Foundation Trust (AGM, CM-B), Newcastle Upon Tyne, United Kingdom; Department of Rehabilitation and Regenerative Medicine (JM), Columbia University Irving Medical Center, New York; Neurorehabilitation Unit (VAS, EA), University of Milan, Neuromuscular Omnicentre Clinical Center, Niguarda Hospital; Unit of Neuromuscular and Neurodegenerative Disorders (ADA, ESB), Bambino Gesù Children's Hospital IRCCS, Rome; Center of Experimental and Translational Myology (CB), IRCCS Istituto Giannina Gaslini, Genoa and Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa; Department of Clinical and Experimental Medicine and Centro Clinico Nemo Sud (SSM), University of Messina, Italy; Leeds Children Hospital (A-MC); The Robert Jones and Agnes Hunt Orthopaedic Hospital (TW), Oswestry; Sheffield Children's Hospital (MTO, LS); MDUK Oxford Neuromuscular Centre & NIHR Oxford Biomedical Research Centre (LS), University of Oxford, United Kingdom; Neuromuscular Reference Center, Department of Paediatrics, University and University Hospital of Liege, Belgium; Royal Hospital for Children (AM), Bristol; Royal Manchester Children's Hospital (IH); University Hospitals Birmingham (DP), United Kingdom; Evelina London Children's Hospital (VLG), London, UK; Departments of Neurology and Pediatrics (DCDV), Columbia University Irving Medical Center, New York; Department of Neurology (BTD), Boston Children's Hospital, Harvard Medical School, Boston, MA; Department of Neurology (JWD), Stanford University, Palo Alto, CA; Department of Paediatrics The Children's Hospital of Philadelphia (OM, ZZ-C), Philadelphia, PA; Nemours Children's Hospital (RSF), University of Central Florida College of Medicine, Orlando; St. Jude Children's Research Hospital (RSF), Memphis, TN; and NIHR Great Ormond Street Hospital Biomedical Research Centre (FM), London, United Kingdom.
Jazyk:	angličtina
Zdroj:	Neurology. Clinical practice [Neurol Clin Pract] 2024 Jun; Vol. 14 (3), pp. e200298. Date of Electronic Publication: 2024 May 17.
DOI:	10.1212/CPJ.0000000000200298
Abstrakt:	Background and Objectives: Nusinersen has shown significant functional motor benefit in the milder types of spinal muscular atrophy (SMA). Less is known on the respiratory outcomes in patients with nusinersen-treated SMA. The aim of this study was to describe changes in respiratory function in pediatric patients with SMA type 2 and 3 on regular treatment with nusinersen within the iSMAc international cohort and to compare their trajectory with the natural history (NH) data published by the consortium in 2020. Methods: This is a 5-year retrospective observational study of pediatric SMA type 2 and nonambulant type 3 (age ≤18 years) treated with nusinersen. The primary objective was to compare the slopes of decline in forced vital capacity % predicted (FVC% pred.), FVC, and age when FVC dropped below 60% between the treated patients and a control group from the natural history cohort. Data on peak cough flow and the use of noninvasive ventilation (NIV) and cough assist were collected. Results: Data were available for 69 treated patients, 53 were SMA type 2 and 16 type 3. The mean (SD) age at first injection was 8.5 (3.2) and 9.7 (3.7) years, respectively. The median (interquartile range) treatment duration was 1 (0.7; 1.9) and 1.2 (0.9; 1.9) years, respectively. At the time of the first nusinersen injection, 24 of 52 (46%) patients with SMA type 2 and 2 of 16 (13%) patients with SMA type 3 were on NIV. Forty-three of 53 (81%) and 4 of 16 (25%) patients used cough device. FVC% pred. in treated patients with SMA type 2 declined annually by 2.3% vs 3.9% in NH ( p = 0.08) and in treated patients with type 3 by 2.6% vs 3.4% NH ( p = 0.59). Patients treated reached FVC <60% later than untreated (12.1 vs 10 years, p = 0.05). A higher percentage of treated vs untreated patients maintained FVC% pred. equal/above their baseline after 12 (65% vs 36%) and 24 (50% vs 24%) months, respectively. NIV use among treated did not significantly change throughout 1-year follow-up. Discussion: This study included the largest real-world cohort of pediatric patients with milder SMA types. The results suggest a positive role of nusinersen in delaying the respiratory decline in patients treated longer than 1 year when compared with natural history. Larger cohorts and longer observation are planned. Classification of Evidence: This study provided Class III evidence that nusinersen slows progression for patients with SMA types 2 and 3 compared with a natural history cohort. Competing Interests: F. Trucco reports participation to Scientific Advisory Boards for Roche UK and teaching initiatives for Biogen, Avexis, Roche, and BREAS. D. Ridout, I. Hughes, Z. Zolkipli-Cunningham, and M. Main report no disclosures. M. Scoto reports participation in Scientific Advisory Boards and teaching initiatives for Avexis, Biogen, and Roche. She is involved as an investigator in clinical trials from Avexis, Biogen, and Roche. In addition, she is the co-principal investigator of the SMA REACH UK clinical network, partially funded by Biogen and Roche. F. Muntoni reports participation in Scientific Advisory Boards and teaching initiatives for Biogen, Roche, and Novartis. He is member of the Rare Disease Scientific Advisory Board for Pfizer. He is involved as an investigator in clinical trials from Novartis, Biogen, and Roche. In addition, he is the principal investigator of the SMA REACH UK clinical network, partially funded by Biogen and Roche. E. Mercuri reports participation in Scientific Advisory Boards and teaching initiatives for Biogen, Roche, Scholar Rock, and Novartis. He is involved as an investigator in clinical trials from Novartis, Biogen, Scholar Rock, and Roche. In addition, he is the principal investigator of the Italian registry participating in iSMAc, partially funded by Biogen, Roche, and Novartis. R. Finkel reports participation in Medical and Scientific Advisory Boards on SMA topics with Novartis, Biogen, Ionis, Roche, Cure SMA, SMA Europe, SMA REACH UK, SMA Foundation, and MDA. Finkel participates as an investigator in SMA-related clinical trials sponsored or supported by Novartis, Biogen, Ionis, Roche, and Scholar Rock. Dr. D. De Vivo reports participation as a consultant in Medical and Scientific Advisory Boards and as an investigator with Novartis, Biogen, Ionis, Roche, PTC, Santhera, Scholar Rock, Sanofi, GliaPharm, Fulcrum Therapeutics, Sarepta, NS Pharma, SMA Foundation, Cure SMA, DoD, NIH, Glut1 Deficiency Foundation, and Hope for Children Research Foundation. B. Darras has served as an ad hoc Scientific Advisory Board member for Novartis, Biogen, Cytokinetics, Vertex, Genentech, Roche, and Sarepta; Steering Committee chair for Roche; and Data Safety Monitoring Board member for Amicus Inc. He has no financial interests in these companies. He has received research support from the NIH/National Institute of Neurological Disorders and Stroke, the Slaney Family Fund for SMA, the Spinal Muscular Atrophy Foundation, CureSMA, and Working on Walking Fund and has received grants from Ionis Pharmaceuticals, Inc, for the ENDEAR, CHERISH, CS2/CS12 studies; from Biogen for CS11; and from Cytokinetics, Sarepta Pharmaceuticals, PTC Therapeutics, Fibrogen, and Summit. O. Mayer reports participation in Advisory Boards for Roche, Biogen, and PTC Therapeutics. He is participating in SMA REACH and iSMAC, partially funded by Biogen. C. Bruno reports participation in Scientific Advisory Boards on SMA topics with Novartis, Biogen, and Roche and participates as a principal investigator in SMA-related clinical trials sponsored by Novartis, Biogen, Ionis, and Roche. S. Messina reports participation in Scientific Advisory Boards and teaching initiatives for Novartis, Biogen, and Roche. She is involved as an investigator in clinical trials from Novartis, Biogen, Scholar Rock, and Roche. M. Pane reports participation in Scientific Advisory Boards and teaching initiatives for Novartis and Biogen. V.A. Sansone provides intellectual support in Advisory Boards and teaching activities for Biogen, Santhera, Sarepta, PTC, Dyne, Triplet, and Novartis. A. D'Amico reports participation in Scientific Advisory Board for Novartis, Roche, and Novartis and teaching initiatives for Biogen. She is also involved as an investigator in clinical trials from Novartis, Biogen, and Roche. In addition, she is an investigator of the Italian registry participating in iSMAc, partially funded by Biogen. E.S. Bertini reports participation in Scientific Advisory Boards for Novartis, Roche, Novartis, and PTC and teaching initiatives for Biogen. He is also involved as an investigator in clinical trials from Novartis, Biogen, Roche, and Novartis. In addition, he is an investigator of the Italian registry participating in iSMAc, partially funded by Biogen. C. Marini-Bettolo reports participation in Scientific Advisory Boards and teaching initiatives for Novartis, Biogen, and Roche. She is involved as an investigator in clinical trials from Novartis. In addition, she is principal investigator for the UK SMA patient registry funded by SMA UK. A. Childs reports participation in Advisory Boards for Novartis, Roche, Biogen, Santhera, and PTC Therapeutics. She is principal investigator for clinical trials supported by Sarepta, Santhera, and PTC Therapeutics. She is participating in SMA REACH and iSMAC, partially funded by Biogen. M. Ong reports participation in Advisory Boards or received consultation fees for Novartis, Roche, Biogen, and CSL Behring. She is participating in SMA REACH and iSMAC, partially funded by Biogen. Dr. A. Mayhew reports participation in Scientific Advisory Boards and teaching initiatives for Biogen and Roche. She is involved as an evaluator at site and acts as an independent consultant to train evaluators in clinical trials from Novartis, Biogen, and Roche. In addition, she is the principal investigator at Newcastle for the SMA REACH UK clinical network, partially funded by Biogen and by SMA UK. J. Montes reports participation as a consultant and on Scientific Advisory Boards for Biogen, Ionis, Roche, and Scholar Rock. G. Coratti reports consultant activities for Novartis, Biogen, Roche, Biologix, and Genesis Pharma. She is involved as a clinical evaluator in clinical trials from Novartis, Biogen, Scholar Rock, and Roche. R. De Sanctis reports consultant activities for Biogen and Roche. He is involved as a clinical evaluator in clinical trials from Novartis, Biogen, Scholar Rock, and Roche. L. Servais reports consultancy/board attendance/lectures for Novartis, Biogen, Roche, Scholar Rock, and BioHaven. A. Majumdar reports participation in Advisory Boards for Novartis, Roche, Biogen, Santhera, and PTC Therapeutics. He is principal investigator for clinical trials supported by Wave Therapeutics. He is participating in SMA REACH and iSMAC, partially funded by Biogen. D. Parasuraman reports participation in Advisory Boards for Roche, Biogen, Sarepta and has had support from PTC Therapeutics. He is principal investigator for clinical trials supported by Roche. He is participating in SMA REACH and iSMAC, partially funded by Biogen. V. Gowda reports participation in Advisory Boards or received consultation fees for Novartis, Roche, Biogen, PTC therapeutics, Wave Life Sciences, Pfizer, and Sarepta Therapeutics. She is participating in SMA REACH and iSMAC, partially funded by Biogen. FT, CB, EB, AD, EM, and MP are members of the ERN NMD (European Reference Networks). Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp. (© 2024 American Academy of Neurology.)
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