title: Broad phenotypic heterogeneity due to a novel SCN1A mutation in a family with genetic epilepsy with febrile seizures plus.
abstract: Genetic (generalized) epilepsy with febrile seizures plus is a familial epilepsy syndrome with marked phenotypic heterogeneity ranging from simple febrile seizure to severe phenotypes. Here we report on a large Israeli family with genetic (generalized) epilepsy with febrile seizures plus and 14 affected individuals. A novel SCN1A missense mutation in exon 21 (p.K1372E) was identified in all affected individuals and 3 unaffected carriers. The proband had Dravet syndrome, whereas febrile seizure plus phenotypes were present in all other affected family members. Simple febrile seizures were not observed. Phenotypes were found at both extremes of the genetic (generalized) epilepsy with febrile seizures plus spectrum and distribution of phenotypes suggested modifying familial, possibly genetic factors. We suggest that families with extreme phenotype distributions can represent prime candidates for the identification of genetic or environmental modifiers.
authors.affiliation: 1Department of Pediatric and Adolescent Neurology, Epilepsy Center, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.
authors.forename: Hadassa
authors.initials: H
authors.lastname: Goldberg-Stern
authors.forename: Sharon
authors.initials: S
authors.lastname: Aharoni
authors.forename: Zaid
authors.initials: Z
authors.lastname: Afawi
authors.forename: Odeya
authors.initials: O
authors.lastname: Bennett
authors.forename: Silke
authors.initials: S
authors.lastname: Appenzeller
authors.forename: Manuela
authors.initials: M
authors.lastname: Pendziwiat
authors.forename: Gregor
authors.initials: G
authors.lastname: Kuhlenbäumer
authors.forename: Lina
authors.initials: L
authors.lastname: Basel-Vanagaite
authors.forename: Avinoam
authors.initials: A
authors.lastname: Shuper
authors.forename: Amos D
authors.initials: AD
authors.lastname: Korczyn
authors.forename: Ingo
authors.initials: I
authors.lastname: Helbig
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D004831:Epilepsies, Myoclonic / Q000150:complications / Q000235:genetics; D004827:Epilepsy / Q000150:complications* / Q000235:genetics*; D005190:Family; D005260:Female; D006801:Humans; D007223:Infant; D007557:Israel; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D062550:NAV1.1 Voltage-Gated Sodium Channel / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D003294:Seizures, Febrile / Q000150:complications* / Q000235:genetics*; D055815:Young Adult
chemical_list: D062550:NAV1.1 Voltage-Gated Sodium Channel; C568242:SCN1A protein, human
keywords: GEFS+; SCN1A; epilepsy genetics; febrile seizure