Generalized Epilepsy With Febrile Seizures Plus, Type 4

For a general phenotypic description and a discussion of genetic heterogeneity of generalized epilepsy with febrile seizures plus (GEFS+), see 604233.

Clinical Features

Audenaert et al. (2005) reported a 4-generation Belgian family with febrile seizures and epilepsy compatible with GEFS+. Eight patients had seizures associated with fevers, but none developed epilepsy later in life. The febrile seizures occurred between ages 6 months and 2.5 years, and were generalized tonic-clonic in all cases. Most seizures were brief, but in 2 individuals they laster longer than 30 minutes. The number of seizures ranged from 1 to 3, except in 1 individual who had a total of 23 seizures. Three patients had epileptic seizures without a history of febrile seizures; however, 1 of these patients was deceased with scant clinical history, and a second patient had a parent with epilepsy who was not part of the Belgian family. The third patient without febrile seizures had a single absence seizure at age 9 months.

Mapping

By genomewide linkage analysis and haplotype analysis in a 4-generation Belgian family segregating febrile seizures and epilepsy compatible with GEFS+, Audenaert et al. (2005) identified a 3.24-cM (4.2-Mb) candidate region on chromosome 2p24 (maximum 2-point lod score of 4.22 at marker D2S305). Further analysis of 50 additional families of Belgian-Dutch origin in which at least 1 individual had febrile seizures showed association with 2p24. Based upon ancestral recombination events, Audenaert et al. (2005) suggested that there is a 2.14-cM region between D2S1360 and D2S2342 that contains a susceptibility locus for febrile seizures and epilepsy in this population.