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James Sutcliffe
Last active: 2/20/2014

Partial and generalized epilepsy with febrile seizures plus and a novel SCN1A mutation.

Abou-Khalil B, Ge Q, Desai R, Ryther R, Bazyk A, Bailey R, Haines JL, Sutcliffe JS, George AL
Neurology. 2001 57 (12): 2265-72

PMID: 11756608 · DOI:10.1212/wnl.57.12.2265

BACKGROUND - Generalized epilepsy with febrile seizures plus (GEFS+) is an autosomal dominant syndrome characterized by febrile seizures (FS) and a variety of afebrile generalized seizure types. GEFS+ has previously been linked to mutations in two genes encoding the voltage-gated sodium channel alpha-subunit (SCN1A) and beta1-subunit (SCN1B). We studied a large family with FS and partial as well as generalized seizure types.

METHODS - All but two living affected family members were interviewed and examined. Information on deceased affected family members was sought. EEG for 11 affected family members and one unaffected family member were obtained. Genetic linkage analysis and mutation screening of SCN1A were performed on blood samples from 16 affected individuals and their first-degree relatives.

RESULTS - There were 27 affected family members; 18 were alive at the time of the study. All affected family members had FS; seven had FS only, and 19 also had afebrile seizures. Eleven individuals continued to have FS beyond 6 years of age. FS were complex in 12 family members, usually with prolonged duration. The index patient had right temporal lobe epilepsy and hippocampal sclerosis. Four other patients had strong historical evidence of temporal lobe epilepsy, and three others had nonlocalizing evidence of partial epilepsy. Pedigree analysis indicated autosomal dominant transmission. All affected individuals who were tested and one asymptomatic individual had a sodium channel mutation of SCN1A, an A-->C transversion at nucleotide 3809 resulting in the substitution of lysine 1270 by threonine in the D3/S2 segment (designated as K1270T).

CONCLUSIONS - Our findings indicate that partial epilepsy preceded by FS can be associated with sodium channel mutations and may represent a variant of GEFS+.

MeSH Terms (24)

Adolescent Adult Aged Age of Onset Amino Acid Sequence Brain Child Child, Preschool Chromosomes, Human, Pair 2 Electroencephalography Epilepsies, Partial Epilepsy, Generalized Female Genetic Linkage Humans Infant Magnetic Resonance Imaging Male Middle Aged Molecular Sequence Data Mutation Pedigree Phenotype Seizures, Febrile

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