Clinical investigation of genetic contributions to childhood-onset epilepsies and epileptic syndromes

Abstract

Although there have been major advances in the understanding of the molecular bases of certain inherited epilepsy syndromes, clinical studies are still needed to verify the possible genetic contributions to common epilepsies. We examined the proportions of positive family histories of epilepsy (within second-degree relatives) and consanguinity (within first-degree relatives) in 311 probands with childhood-onset epilepsy, and found that they had high family history rates of epilepsy (19.3%) and consanguinity (6.1%). A positive family history of epilepsy was found more in probands with generalized epilepsy than in ones with localization-related epilepsy, and more in probands with idiopathic/cryptogenic epilepsy than in ones with symptomatic epilepsy. However, on analysis after the symptomatic epilepsies had been divided into two categories, probands with pre- or perinatal symptomatic generalized epilepsy and ones with postnatal symptomatic localization-related epilepsy showed high positive family history rates, similar to ones with idiopathic/cryptogenic epilepsy. On the other hand, a positive family history of consanguinity was noted more in probands with generalized epilepsy than in ones with localization-related epilepsy, but there was no significant difference between probands with idiopathic/cryptogenic epilepsy and ones with symptomatic epilepsy. These findings suggest that in addition to the hereditary effect on idiopathic/cryptogenic epilepsy, a genetic susceptibility may contribute to the development of pre- or perinatal symptomatic generalized epilepsy, and to that of postnatal symptomatic localization-related epilepsy. Furthermore, a genetic predisposition seems to have an influence through consanguinity on the etiologies of both idiopathic/cryptogenic and symptomatic generalized epilepsies.