Abstracts

Febrile seizures are common, affecting 2-5% of all children. Although often considered a benign condition, complex febrile seizures are a risk factor for temporal lobe epilepsy. Identification of the genes involved in febrile seizures may translate into better diagnosis and treatment of epilepsy. Six loci for autosomal dominant febrile seizures have been reported (8q,19p,2q,6q,5q, 21q, and 12q), including a locus on chromosome 12q that was found in a large Belgian family with familial temporal lobe epilepsy with febrile seizures (Claes et al., J Med Genet 2004; 41:710-714). However, the altered genes have not yet been identified for any of these loci. A large North American Caucasian family with seven affected individuals with febrile seizures was identified. Detailed history and blood was taken from 18 family members after obtaining consent; medical records were reviewed when available. After excluding known loci for febrile seizures, a genome wide scan was performed using Research Genetics MapPairs (Invitrogen) 18cM microsatellite markers. Five affected individuals had complex febrile seizures lasting longer than five minutes, and two had seizures with focal features. Three also had afebrile seizures that remitted prior to age 6. None had complex partial seizures or features of temporal lobe epilepsy. One patient developed medically intractable partial epilepsy following an episode of status epilepticus and hypoxia, after which he was noted to have developed a parietal lesion on MRI imaging. Nonpenetrance of the trait was seen in two individuals. Several markers on chromosome 12 gave a two-point lod score [gt]2, including PAH (2.58) and D12S1300 (2.31). This overlaps with and confirms the locus previously reported by Claes et al although analysis of recombination events did not further narrow this locus. Candidate genes in the region have been sequenced in affected and unaffected individuals from this family. This study confirms the broad phenotype of epilepsy linked to chromosome 12q, including complex febrile and afebrile seizures, and differs from the Belgian family in that none manifested temporal lobe epilepsy. Although there are more than 50 genes in the candidate region of 8.7 Mb, none are ion channel genes, and therefore identification of this locus may reveal new and novel mechanisms for familial epilepsy. (Supported by NINDS K12 Award NS01690 (C.A.G.), National Epifellows Reserach Grant (C.A.G.).)