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Solving the Etiology of Developmental and Epileptic Encephalopathy with Spike-Wave Activation in Sleep (D/EE-SWAS).
Viswanathan, Sindhu; Oliver, Karen L; Regan, Brigid M; Schneider, Amy L; Myers, Candace T; Mehaffey, Michele G; LaCroix, Amy J; Antony, Jayne; Webster, Richard; Cardamone, Michael; Subramanian, Gopinath M; Chiu, Annie T G; Roza, Eugenia; Teleanu, Raluca I; Malone, Stephen; Leventer, Richard J; Gill, Deepak; Berkovic, Samuel F; Hildebrand, Michael S; Goad, Beatrice S; Howell, Katherine B; Symonds, Joseph D; Brunklaus, Andreas; Sadleir, Lynette G; Zuberi, Sameer M; Mefford, Heather C; Scheffer, Ingrid E.
Afiliación
  • Viswanathan S; Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Melbourne, Australia.
  • Oliver KL; Department of Paediatrics, Hospital Pulau Pinang, George Town, Malaysia.
  • Regan BM; Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Melbourne, Australia.
  • Schneider AL; Population Health and Immunity Division, the Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
  • Myers CT; Department of Medical Biology, the University of Melbourne, Melbourne, Australia.
  • Mehaffey MG; Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Melbourne, Australia.
  • LaCroix AJ; Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Melbourne, Australia.
  • Antony J; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA.
  • Webster R; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington, USA.
  • Cardamone M; Department of Pediatrics, Division of Genetic Medicine, University of Washington, Seattle, Washington, USA.
  • Subramanian GM; Department of Pediatrics, Division of Genetic Medicine, University of Washington, Seattle, Washington, USA.
  • Chiu ATG; T.Y. Nelson Department of Neurology and Neurosurgery, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, Sydney, Australia.
  • Roza E; T.Y. Nelson Department of Neurology and Neurosurgery, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, Sydney, Australia.
  • Teleanu RI; Department of Paediatric Neurology, Sydney Children's Hospital, Randwick; School of Clinical Medicine, UNSW Sydney, Sydney, Australia.
  • Malone S; Department of Paediatric Neurology, John Hunter Children's Hospital, New Lambton Heights, Australia.
  • Leventer RJ; Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Melbourne, Australia.
  • Gill D; Faculty of Medicine, Clinical Neurosciences Department, Paediatric Neurology, Carol Davila University of Medicine and Pharmacy, București, Romania.
  • Berkovic SF; Pediatric Neurology Department, Dr. Victor Gomoiu Children's Hospital, București, Romania.
  • Hildebrand MS; Faculty of Medicine, Clinical Neurosciences Department, Paediatric Neurology, Carol Davila University of Medicine and Pharmacy, București, Romania.
  • Goad BS; Pediatric Neurology Department, Dr. Victor Gomoiu Children's Hospital, București, Romania.
  • Howell KB; Centre for Advanced Imaging, University of Queensland, St Lucia, Australia.
  • Symonds JD; Neurosciences Department, Queensland Children's Hospital, South Brisbane, Australia.
  • Brunklaus A; Department of Neurology, Royal Children's Hospital, University of Melbourne, Melbourne, Australia.
  • Sadleir LG; Neuroscience Research Group, Murdoch Children's Research Institute, Melbourne, Australia.
  • Zuberi SM; T.Y. Nelson Department of Neurology and Neurosurgery, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, Sydney, Australia.
  • Mefford HC; Kids Neuroscience Centre, Kids Research Institute, Sydney, Australia.
  • Scheffer IE; Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Melbourne, Australia.
Ann Neurol ; 96(5): 932-943, 2024 Nov.
Article en En | MEDLINE | ID: mdl-39096015
ABSTRACT

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;96932-943.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Espasmos Infantiles Límite: Adolescent / Adult / Child / Child, preschool / Female / Humans / Infant / Male Idioma: En Revista: Ann Neurol Año: 2024 Tipo del documento: Article País de afiliación: Australia
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Espasmos Infantiles Límite: Adolescent / Adult / Child / Child, preschool / Female / Humans / Infant / Male Idioma: En Revista: Ann Neurol Año: 2024 Tipo del documento: Article País de afiliación: Australia