Clinical and genetic analysis of a new multigenerational pedigree with GEFS+ (generalized epilepsy with febrile seizures plus)

Febrile seizures affect 2-5% of all children younger than 6 years. A small proportion of children with febrile seizures later develop epilepsy. The syndrome of generalized epilepsy with febrile seizures plus (GEFS(+)) is a heterogeneous disorder characterized by febrile seizures that may persist beyond age 6 years and nonfebrile seizures. Several genes have teen localized for FS by linkage analysis, and three GEFS(+) genes (SCN1A, SCN1B, GABRG2) have been identified. We identified a large multi generational family with GEFS(+) in France. All affected members had FSs. Among them, seven had other types of epileptic seizures including FSs after age 6 years, nonfebrile generalized seizures, or partial seizures later in life. Genetic linkage study excluded the candidate genes and loci for FS and GEFS(+), thus proving the existence of a new GEFS(+) genetic locus underlying the phenotype observed in this family.