title: Autosomal dominant epilepsy with febrile seizures plus with missense mutations of the (Na+)-channel alpha 1 subunit gene, SCN1A.
abstract: Evidence that febrile seizures have a strong genetic predisposition has been well documented. In families of probands with multiple febrile convulsions, an autosomal dominant inheritance with reduced penetrance is suspected. Four candidate loci for febrile seizures have been suggested to date; FEB1 on 8q13-q21, FEB2 on 19p, FEB3 on 2q23-q24, and FEB4 on 5q14-15. A missense mutation was identified in the voltage-gated sodium (Na(+))-channel beta 1 subunit gene, SCN1B at chromosome 19p13.1 in generalized epilepsy with the febrile seizures plus type 1 (GEFS+1) family. Several missense mutations of the (Na(+))-channel alpha 1 subunit (Nav1.1) gene, SCN1A were also identified in GEFS+2 families at chromosome 2q23-q24.3. The aim of this report is precisely to describe the phenotypes of Japanese patients with novel SCN1A mutations and to reevaluate the entity of GEFS+. Four family members over three generations and one isolated (phenotypically sporadic) case with SCN1A mutations were clinically investigated. The common seizure type in these patients was febrile and afebrile generalized tonic-clonic seizures (FS+). In addition to FS+, partial epilepsy phenotypes were suspected in all affected family members and electroencephalographically confirmed in three patients of two families. GEFS+ is genetically and clinically heterogeneous, and associated with generalized epilepsy and partial epilepsy as well. The spectrum of GEFS+ should be expanded to include partial epilepsies and better to be termed autosomal dominant epilepsy with febrile seizures plus (ADEFS+).
authors.affiliation: Department of Pediatrics, Shiga Medical Center for Children, 5-7-30 Moriyama, Moriyama 524-0022, Japan. ito-mccs@mx.biwa.ne.jp
authors.forename: M
authors.initials: M
authors.lastname: Ito
authors.forename: H
authors.initials: H
authors.lastname: Nagafuji
authors.forename: H
authors.initials: H
authors.lastname: Okazawa
authors.forename: K
authors.initials: K
authors.lastname: Yamakawa
authors.forename: T
authors.initials: T
authors.lastname: Sugawara
authors.forename: E
authors.initials: E
authors.lastname: Mazaki-Miyazaki
authors.forename: S
authors.initials: S
authors.lastname: Hirose
authors.forename: G
authors.initials: G
authors.lastname: Fukuma
authors.forename: A
authors.initials: A
authors.lastname: Mitsudome
authors.forename: K
authors.initials: K
authors.lastname: Wada
authors.forename: S
authors.initials: S
authors.lastname: Kaneko
mesh_terms: D000328:Adult; D002648:Child; D002675:Child, Preschool; D025063:Chromosome Disorders / Q000235:genetics; D004569:Electroencephalography; D004827:Epilepsy / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D003294:Seizures, Febrile / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D015222:Sodium Channels / Q000235:genetics*
chemical_list: D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; D015222:Sodium Channels