Solving the Etiology of Developmental and Epileptic Encephalopathy with Spike-Wave Activation in Sleep (D/EE-SWAS).

Autor: Viswanathan S; Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Melbourne, Australia.; Department of Paediatrics, Hospital Pulau Pinang, George Town, Malaysia., Oliver KL; Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Melbourne, Australia.; Population Health and Immunity Division, the Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.; Department of Medical Biology, the University of Melbourne, Melbourne, Australia., Regan BM; Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Melbourne, Australia., Schneider AL; Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Melbourne, Australia., Myers CT; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA., Mehaffey MG; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA.; Department of Pediatrics, Division of Genetic Medicine, University of Washington, Seattle, Washington, USA., LaCroix AJ; Department of Pediatrics, Division of Genetic Medicine, University of Washington, Seattle, Washington, USA., Antony J; T.Y. Nelson Department of Neurology and Neurosurgery, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, Sydney, Australia., Webster R; T.Y. Nelson Department of Neurology and Neurosurgery, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, Sydney, Australia., Cardamone M; Department of Paediatric Neurology, Sydney Children's Hospital, Randwick; School of Clinical Medicine, UNSW Sydney, Sydney, Australia., Subramanian GM; Department of Paediatric Neurology, John Hunter Children's Hospital, New Lambton Heights, Australia., Chiu ATG; Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Melbourne, Australia., Roza E; Faculty of Medicine, Clinical Neurosciences Department, Paediatric Neurology, Carol Davila University of Medicine and Pharmacy, București, Romania.; Pediatric Neurology Department, Dr. Victor Gomoiu Children's Hospital, București, Romania., Teleanu RI; Faculty of Medicine, Clinical Neurosciences Department, Paediatric Neurology, Carol Davila University of Medicine and Pharmacy, București, Romania.; Pediatric Neurology Department, Dr. Victor Gomoiu Children's Hospital, București, Romania., Malone S; Centre for Advanced Imaging, University of Queensland, St Lucia, Australia.; Neurosciences Department, Queensland Children's Hospital, South Brisbane, Australia., Leventer RJ; Department of Neurology, Royal Children's Hospital, University of Melbourne, Melbourne, Australia.; Neuroscience Research Group, Murdoch Children's Research Institute, Melbourne, Australia., Gill D; T.Y. Nelson Department of Neurology and Neurosurgery, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, Sydney, Australia.; Kids Neuroscience Centre, Kids Research Institute, Sydney, Australia., Berkovic SF; Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Melbourne, Australia., Hildebrand MS; Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Melbourne, Australia.; Neuroscience Research Group, Murdoch Children's Research Institute, Melbourne, Australia., Goad BS; Department of Neurology, Royal Children's Hospital, University of Melbourne, Melbourne, Australia.; Neuroscience Research Group, Murdoch Children's Research Institute, Melbourne, Australia., Howell KB; Department of Neurology, Royal Children's Hospital, University of Melbourne, Melbourne, Australia.; Neuroscience Research Group, Murdoch Children's Research Institute, Melbourne, Australia., Symonds JD; School of Health and Wellbeing, University of Glasgow, Glasgow, UK.; The Paediatric Neurosciences Research Group, Royal Hospital for Children, Glasgow, UK., Brunklaus A; School of Health and Wellbeing, University of Glasgow, Glasgow, UK.; The Paediatric Neurosciences Research Group, Royal Hospital for Children, Glasgow, UK., Sadleir LG; Department of Paediatrics and Child Health, University of Otago Wellington, Wellington, New Zealand., Zuberi SM; School of Health and Wellbeing, University of Glasgow, Glasgow, UK.; The Paediatric Neurosciences Research Group, Royal Hospital for Children, Glasgow, UK., Mefford HC; Department of Pediatrics, Division of Genetic Medicine, University of Washington, Seattle, Washington, USA.; Centre for Pediatric Neurological Disease Research, St. Jude Children's Research Hospital, Memphis, Tennessee, USA., Scheffer IE; Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Melbourne, Australia.; Department of Neurology, Royal Children's Hospital, University of Melbourne, Melbourne, Australia.; Neuroscience Research Group, Murdoch Children's Research Institute, Melbourne, Australia.; The Florey Institute of Neurosciences and Mental Health, Melbourne, Australia.
Jazyk: angličtina
Zdroj: Annals of neurology [Ann Neurol] 2024 Nov; Vol. 96 (5), pp. 932-943. Date of Electronic Publication: 2024 Aug 02.
DOI: 10.1002/ana.27041
Abstrakt: Objective: To understand the etiological landscape and phenotypic differences between 2 developmental and epileptic encephalopathy (DEE) syndromes: DEE with spike-wave activation in sleep (DEE-SWAS) and epileptic encephalopathy with spike-wave activation in sleep (EE-SWAS).
Methods: All patients fulfilled International League Against Epilepsy (ILAE) DEE-SWAS or EE-SWAS criteria with a Core cohort (n = 91) drawn from our Epilepsy Genetics research program, together with 10 etiologically solved patients referred by collaborators in the Expanded cohort (n = 101). Detailed phenotyping and analysis of molecular genetic results were performed. We compared the phenotypic features of individuals with DEE-SWAS and EE-SWAS. Brain-specific gene co-expression analysis was performed for D/EE-SWAS genes.
Results: We identified the etiology in 42/91 (46%) patients in our Core cohort, including 29/44 (66%) with DEE-SWAS and 13/47 (28%) with EE-SWAS. A genetic etiology was identified in 31/91 (34%). D/EE-SWAS genes were highly co-expressed in brain, highlighting the importance of channelopathies and transcriptional regulators. Structural etiologies were found in 12/91 (13%) individuals. We identified 10 novel D/EE-SWAS genes with a range of functions: ATP1A2, CACNA1A, FOXP1, GRIN1, KCNMA1, KCNQ3, PPFIA3, PUF60, SETD1B, and ZBTB18, and 2 novel copy number variants, 17p11.2 duplication and 5q22 deletion. Although developmental regression patterns were similar in both syndromes, DEE-SWAS was associated with a longer duration of epilepsy and poorer intellectual outcome than EE-SWAS.
Interpretation: DEE-SWAS and EE-SWAS have highly heterogeneous genetic and structural etiologies. Phenotypic analysis highlights valuable clinical differences between DEE-SWAS and EE-SWAS which inform clinical care and prognostic counseling. Our etiological findings pave the way for the development of precision therapies. ANN NEUROL 2024;96:932-943.
(© 2024 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)
Databáze: MEDLINE
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