Not all SCN1A epileptic encephalopathies are Dravet syndrome
AuthorSadleir, LG; Mountier, EI; Gill, D; Davis, S; Joshi, C; DeVile, C; Kurian, MA; Mandelstam, S; Wirrell, E; Nickels, KC; ...
PublisherLIPPINCOTT WILLIAMS & WILKINS
AffiliationMedicine (Austin & Northern Health)
Document TypeJournal Article
CitationsSadleir, L. G., Mountier, E. I., Gill, D., Davis, S., Joshi, C., DeVile, C., Kurian, M. A., Mandelstam, S., Wirrell, E., Nickels, K. C., Murali, H. R., Carvill, G., Myers, C. T., Mefford, H. C. & Scheffer, I. E. (2017). Not all SCN1A epileptic encephalopathies are Dravet syndrome. NEUROLOGY, 89 (10), pp.1035-1042. https://doi.org/10.1212/WNL.0000000000004331.
Access StatusOpen Access
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.
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