HEREDITARY FEBRILE SEIZURES - PHENOTYPE AND EVIDENCE FOR A CHROMOSOME19P LOCUS

The occurrence of febrile seizures (FSs) in large autosomal dominant F S kindreds makes possible accurate delineation of the pure clinical ph enotype of hereditary FS among secondary FS cases, and the identificat ion of gene loci causing susceptibility to FS. Recently FS gene loci o n chromosomes 8 and 19 were identified. We studied the phenotype of FS in four large families in which FS is an autosomal dominant trait. Am ong 30 affected secondary FS cases, mean age of onset was 16.3 months (range 4 to 36 months), sex ratio was equal, and 43% were complex (13 of 30). Among these 30 secondary FS cases, the mean number of FSs was 2.1, half had only a single FS, and none had afebrile seizures. Penetr ance was 0.67, approximately the same as in our previous larger group of 40 multicase FS families (0.64). The occurrence of DPT encephalopat hy in a sib of a patient with FS raises the possibility that these two etiologies are related. Linkage studies showed that one of the four f amilies (Family 1) was linked to chromosome 19p markers, none of the f amilies was linked to chromosome 8q markers, and the largest FS family (Kindred 6) was unlinked to either 19p or 8q markers, supporting the hypothesis of genetic heterogeneity for FS. Am. J. Med. Genet. 79:354- 361, 1998. (C) 1998 Wiley-Liss, Inc.