The genetics of febrile seizures (FS) are reviewed by members of the Department of Pediatrics, Fukuoka University; Department of Neuropsychiatry, Hirosaki University, Japan; and National Institutes of Health, Research Triangle Park, NC, USA. Several genetic loci for FS have been mapped, but the exact molecular mechanism is unknown. Mutations have been found in genes encoding Na+ channel subunits and the g2 subunit of gamma amino-butyric acid (GABA)A receptors. These channels are associated with autosomal dominant epilepsy with FS plus, generalized epilepsy with FS plus, and with severe myoclonic epilepsy in infancy that often begins with a prolonged FS. Various Na channels and GABAA receptors in the brain are probably involved in the pathogenesis of frequent FS and also, in simple FS. Genetic linkage analyses have mapped FS to four loci, FEB1,2,3 and 4, in chromosomes 8ql3, 19p, 2q23-q24, and 5ql4-ql5, respectively. [1]

COMMENT. The determination of the molecular genetic mechanism of FS may lead to more specific therapies. FS occur with increased frequency among family members of patients with FS. Tsuboi (1977) reported 17% of parents and 22% of siblings of FS probands affected; 30% of siblings are affected if one parent has a history of FS [2]. An analysis of 2,109 patients with FS reported between 1948 and 1963 in 12 different publications showed a mean familial incidence of 17% (range 2 to 58%) (Millichap, 1968).