TY  - JOUR
AU  - Sadleir, LG
AU  - Mountier, EI
AU  - Gill, D
AU  - Davis, S
AU  - Joshi, C
AU  - DeVile, C
AU  - Kurian, MA
AU  - Mandelstam, S
AU  - Wirrell, E
AU  - Nickels, KC
AU  - Murali, HR
AU  - Carvill, G
AU  - Myers, CT
AU  - Mefford, HC
AU  - Scheffer, IE
Y2  - 2020/12/21
Y1  - 2017/09/05
SN  - 0028-3878
UR  - http://hdl.handle.net/11343/256612
AB  - 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.
LA  - English
PB  - LIPPINCOTT WILLIAMS & WILKINS
T1  - Not all SCN1A epileptic encephalopathies are Dravet syndrome
DO  - 10.1212/WNL.0000000000004331
IS  - Neurology
VL  - 89
IS  - 10
SP  - 1035-1042
L1  - /bitstream/handle/11343/256612/PMC5589790.pdf?sequence=1&isAllowed=y
ER  -