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Title: Not all SCN1A epileptic encephalopathies are Dravet syndrome: early profound Thr226Met phenotype
Austin Authors: Sadleir, Lynette G;Mountier, Emily I;Gill, Deepak;Davis, Suzanne;Joshi, Charuta;DeVile, Catherine;Kurian, Manju A;Mandelstam, Simone;Wirrell, Elaine;Nickels, Katherine C;Murali, Hema R;Carvill, Gemma;Myers, Candace T;Mefford, Heather C;Scheffer, Ingrid E 
Affiliation: Department of Paediatrics and Child Health, University of Otago, Wellington, New Zealand
Department of Neurology, University of Sydney, Sydney, NSW, Australia
Department of Neurology, Starship Children's Health, Auckland, New Zealand
Department of Neurology, Children's Hospital Colorado, Anschutz Medical Campus, University of Colorado, Denver, CO, USA
Department of Neurology, Great Ormond Street Hospital for Children, London, UK
Developmental Neurosciences, UCL Great Ormond Street Institute of Child Health, London, UK
Wellcome Trust Sanger Institute (DDD Study Group), Hinxton, Cambridge, UK
Departments of Paediatrics and Radiology, University of Melbourne, Melbourne, Victoria, Australia
The Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia
Department of Medical Imaging, Royal Children's Hospital, Melbourne, Victoria, Australia
Department of Neurology, Mayo Clinic, Rochester, MN, USA
Department of Neurology, Marshfield Clinic, WI, USA
Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA, USA
Departments of Medicine and Paediatrics, University of Melbourne, Austin Health and Royal Children's Hospital, Victoria, Australia
Issue Date: 9-Aug-2017
Date: 2017-08-09
Publication information: Neurology 2017; 8(31): 51522-51529
Abstract: OBJECTIVE: To define a distinct SCN1A developmental and epileptic encephalopathy with early onset, profound impairment, and movement disorder. METHODS: A case series of 9 children were identified with a profound developmental and epileptic encephalopathy and SCN1A mutation. RESULTS: We identified 9 children 3 to 12 years of age; 7 were male. Seizure onset was at 6 to 12 weeks with hemiclonic seizures, bilateral tonic-clonic seizures, or spasms. All children had profound developmental impairment and were nonverbal and nonambulatory, and 7 of 9 required a gastrostomy. A hyperkinetic movement disorder occurred in all and was characterized by dystonia and choreoathetosis with prominent oral dyskinesia and onset from 2 to 20 months of age. Eight had a recurrent missense SCN1A mutation, p.Thr226Met. The remaining child had the missense mutation p.Pro1345Ser. The mutation arose de novo in 8 of 9; for the remaining case, the mother was negative and the father was unavailable. CONCLUSIONS: Here, we present a phenotype-genotype correlation for SCN1A. We describe a distinct SCN1A phenotype, early infantile SCN1A encephalopathy, which is readily distinguishable from the well-recognized entities of Dravet syndrome and genetic epilepsy with febrile seizures plus. This disorder has an earlier age at onset, profound developmental impairment, and a distinctive hyperkinetic movement disorder, setting it apart from Dravet syndrome. Remarkably, 8 of 9 children had the recurrent missense mutation p.Thr226Met.
DOI: 10.1212/WNL.0000000000004331
ORCID: 0000-0002-2311-2174
Journal: Neurology
PubMed URL:
Type: Journal Article
Appears in Collections:Journal articles

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