Abstracts

RATIONALE: Although the importance of the contribution of genetic factors to risk for the occurrence of epilepsy has been well-documented, the extent to which genetic factors might impact upon epilepsy and seizure type is less well understood. This study was undertaken to characterize the degree to which parents and offspring who are concordant for a history of seizures are also concordant for the type of epilepsy/seizures they experience.
METHODS: Participants in the population-based Mid-Atlantic Twin Registry and the Norwegian Twin Panel were screened using either a mailed questionnaire or a structured telephone interview to identify twins reporting a positive history of seizures in themselves or family members. Based upon an evaluation of medical history information and detailed clinical interviews, seizures and syndromes were classified in those in whom a positive history of seizures could be validated using the ILAE classifications. Epilepsy/seizure classifications in validated parent-offspring pairs concordant for a history of seizures were analyzed and the results obtained used to assess the degree of similiarity in epilepsy/seizure type among pair members.
RESULTS: Among 19,416 twin pairs for whom family health history information was available, 2,277 reported a history of seizures of some type in themselves or a family member. Thus far a history of seizures has been validated and classified in 261 seizure-concordant parent-offspring pairs. Among pairs, 47.5% were concordant for overall syndrome type with the majority being of mixed syndrome type. The sample of syndrome concordant pairs includes 99 (80%) concordant for febrile seizures; 10 for localization-related syndromes (50% of which were concordant for subtype); and 15 for generalized epilepsy (80% of which were concordant for subtype). Among pairs containing at least one member with a localization-related syndrome, 7/8 idiopathic, 16/16 symptomatic and 28/32 cryptogenic were of mixed syndrome type. For pairs containing at least one member with a generalized epilepsy type, 44/53 idiopathic, 2/2 cryptogenic and 2/2 symptomatic-nonspecific etiology were of mixed syndrome type.
CONCLUSIONS: With the exception of febile seizures, relatively few parent-offspring pairs were found to be concordant for epilepsy syndrome type. The large percentage of syndrome discordant parent-offspring pairs observed in this sample and the consistency of this finding for both localization-related and generalized epilepsy syndrome types suggests that seizure susceptibility genes rather than genes responsible for determining specific syndromes may account for the majority of the genetic contribution to seizure risk.
Support: Supported by NIH Grants NS 31564 and N525630.