title: Phenotypes and genotypes in epilepsy with febrile seizures plus.
abstract: In the last several years, mutations of sodium channel genes, SCN1A, SCN2A, and SCN1B, and GABA(A) receptor gene, GABRG2 were identified as causes of some febrile seizures related epilepsies. In 19 unrelated Japanese families whose probands had febrile seizures plus or epilepsy following febrile seizures plus, we identified 2 missense mutations of SCN1A to be responsible for the seizure phenotypes in two FS+ families and another mutation of SCN2A in one family. The combined frequency of SCN1A, SCN2A, SCN1B, SCN2B, and GABRG2 mutations in Japanese patients with FS+ was 15.8%. One family, which had R188W mutation in SCN2A, showed digenic inheritance, and another modifier gene was thought to take part in the seizure phenotype. The phenotypes of probands were FS+ in 5, FS+ and partial epilepsy in 10, FS+ and generalized epilepsy in 3, and FS+ and unclassified epilepsy in 1. We proposed the term epilepsy with febrile seizures plus (EFS+), because autosomal-dominant inheritance in EFS+ might be rare, and most of EFS+ display a complex pattern of inheritance, even when it appears to be an autosomal-dominant inheritance. There is a possibility of simultaneous involvement of multiple genes for seizure phenotypes.
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: K
authors.initials: K
authors.lastname: Yamakawa
authors.forename: T
authors.initials: T
authors.lastname: Sugawara
authors.forename: S
authors.initials: S
authors.lastname: Hirose
authors.forename: G
authors.initials: G
authors.lastname: Fukuma
authors.forename: S
authors.initials: S
authors.lastname: Kaneko
mesh_terms: D000293:Adolescent; D000367:Age Factors; D002648:Child; D004827:Epilepsy / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D062550:NAV1.1 Voltage-Gated Sodium Channel; D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011963:Receptors, GABA-A / Q000235:genetics*; D003294:Seizures, Febrile / Q000235:genetics*; D015222:Sodium Channels / Q000235:genetics*
chemical_list: D062550:NAV1.1 Voltage-Gated Sodium Channel; D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D011963:Receptors, GABA-A; C568242:SCN1A protein, human; C568251:SCN2A protein, human; D015222:Sodium Channels