Not all SCN1A epileptic encephalopathies are Dravet syndrome

作者：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^*

来源：Neurology, 2017, 89(10): 1035-1042.

DOI：10.1212/WNL.0000000000004331

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.

• 出版日期2017-9-5