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Title: Not all SCN1A epileptic encephalopathies are Dravet syndrome: early profound Thr226Met phenotype
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
Issue Date: 9-Aug-2017
EDate: 2017-08-09
Citation: Neurology 2017; online first: 9 August
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
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Type: Journal Article
Appears in Collections:Journal articles

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