title: A novel inherited SCN1A mutation associated with GEFS+ in benign and encephalopathic epilepsy.
abstract: Generalized epilepsy with febrile seizures plus (GEFS+) is an autosomal dominant condition often caused by mutations in SCN1A that usually first manifests as childhood simple febrile seizures but may progress to a variety of afebrile generalized seizure types. Here, we describe the case of an 8-year-old boy with a novel SCN1A mutation who developed febrile seizures at 10months of age which eventually advanced to frequent afebrile tonic-clonic seizures. His condition was unresponsive to several antiepileptic drugs and the ketogenic diet, and he experienced gradual cognitive decline. The patient's father carries the same novel mutation, but he only experienced childhood simple febrile seizures. SCN1A mutations display incomplete penetrance and variable expressivity, and the resulting severity may depend on the location and type of mutation, whether the mutation was spontaneous or inherited, and the effect of modifying alleles. The identification of novel pathogenic SCN1A mutations may eventually advance therapeutic development and prognostic capabilities.
authors.affiliation: Yale Comprehensive Epilepsy Center, Department of Neurology, New Haven, CT 06520-8018, United States. Electronic address: angela.gauthier@yale.edu.
authors.forename: Angela C
authors.initials: AC
authors.lastname: Gauthier
authors.affiliation: Stony Brook University Medical Center, Department of Neurology, Stony Brook, NY 11794, United States; Yale Comprehensive Epilepsy Center, Department of Neurology, New Haven, CT 06520-8018, United States. Electronic address: lmanganas@yahoo.com.
authors.forename: Louis N
authors.initials: LN
authors.lastname: Manganas
authors.affiliation: Yale Comprehensive Epilepsy Center, Department of Neurology, New Haven, CT 06520-8018, United States. Electronic address: Richard.mattson@yale.edu.
authors.forename: Richard H
authors.initials: RH
authors.lastname: Mattson
mesh_terms: D000328:Adult; D002648:Child; D004829:Epilepsy, Generalized / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D062550:NAV1.1 Voltage-Gated Sodium Channel / Q000235:genetics*; D010375:Pedigree; D003294:Seizures, Febrile / Q000175:diagnosis / Q000235:genetics*
chemical_list: D062550:NAV1.1 Voltage-Gated Sodium Channel; C568242:SCN1A protein, human
keywords: Epilepsy; Febrile seizures; Generalized epilepsy with febrile seizures plus; Mutation; SCN1A sodium channel alpha subunit