Generalized epilepsy with febrile seizures plus and classical idiopathic generalized epilepsy

ABSTRACT

The idiopathic generalized epilepsies (IGE) comprise two major groups the classical IGE and generalized epilepsy with febrile seizures plus (GEFS+). The classical IGE syndromes include childhood absence epilepsy; juvenile absence epilepsy; juvenile myoclonic epilepsy; and epilepsy with generalized tonic-clonic seizures alone. GEFS+ is a familial epilepsy syndrome, characterized by a spectrum of phenotypes. The phenotypes of GEFS+ include febrile seizures (FS), febrile seizures plus (FS+), FS/ FS+ and absences, myoclonic, atonic or partial seizures, myoclonic-astatic epilepsy and severe myoclonic epilepsy of infancy. Our study of 121 individuals in 20 families, where 84 had previously recognized GEFS+ phenotypes, expands the phenotypic spectrum of GEFS+ syndrome to include afebrile generalized tonic-clonic seizures with generalized spike wave or normal EEG in the absence of FS. To date, there are three ion channel genes (SCN1A, SCN1B and GABRG2) confi rmed as having a role in GEFS+, but none has been implicated in the majority of patients with GEFS+ phenotypes, such as those found in small families. Indeed it is likely that in most families, GEFS+ is a polygenic disorder resulting from the cumulative effect of a number of genes of lesser effect rather than the genes so far characterized in the few large families ascertained. Small GEFS+ families and bilineal inheritance in some add support for complex inheritance in a signifi cant proportion of families. The phenotypes of classical IGE occur in some GEFS+ families. The percentage of classical IGE phenotypes is 9% (11/121) of affected individuals in our study. This suggests that classical IGE phenotypes and GEFS+ phenotypes overlap in some GEFS+ families. Our study provides new insights into the inter-relationship of GEFS+ and classical IGE, where shared genetic determinants probably account for the overlap of these syndromes in some families.