The genetics of febrile seizures and related epilepsy syndromes.
Febrile seizures (FS) may represent the most common seizure disorder in childhood and are known to be associated with putative genetic predispositions. Nevertheless, molecular genetic approaches toward understanding FS have been just initiated this decade. Recently, several genetic loci for FS have been mapped thereby assuring the genetic heterogeneity of FS. However, the exact molecular mechanisms of FS are yet to be elucidated. Genetic defects have been recently identified in autosomal dominant epilepsy with FS plus or generalized epilepsy with FS plus. The underlying mutations were found in genes encoding several Na+ channel subunits and the gamma2 subunit of gamma amino-butyric acid (GABA)A receptors in the brain. Furthermore, both channels are also associated with severe myoclonic epilepsy in infancy, where the seizure attacks often begin with prolonged FS and are precipitated by fever even afterwards. Na+ channels are associated with other temperature-sensitive disorders, and GABA(A) receptors are known to play an important role in the pathogenesis of FS. These lines of evidence suggest the involvement of various Na+ channels, GABA(A) receptors and additional auxiliary proteins in the pathogenesis of frequent FS and even in simple FS. This hypothesis may facilitate our understanding of the genetic background of FS.
Hirose
Shinichi
S
Department of Pediatrics, School of Medicine, Fukuoka University, 45-1, 7-chome Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan. hirose@fukuoka-u.ac.jp
Mohney
Robert P
RP
Okada
Motohiro
M
Kaneko
Sunao
S
Mitsudome
Akihisa
A
D001330:Electronic Data Processing / Q000379:methods; D004831:Epilepsies, Myoclonic / Q000150:complications / Q000235:genetics; D004829:Epilepsy, Generalized / Q000150:complications / Q000235:genetics; D008040:Genetic Linkage; D006801:Humans; D008967:Molecular Biology; D009154:Mutation; D010375:Pedigree; D011963:Receptors, GABA-A / Q000235:genetics*; D003294:Seizures, Febrile / Q000150:complications / Q000235:genetics*; D015222:Sodium Channels / Q000235:genetics
D011963:Receptors, GABA-A; D015222:Sodium Channels