Abstracts

Rationale: Although genetic factors are recognized as important contributors to risk for epilepsy, their role in the determination of a specific epilepsy syndrome type is less clear. This study was undertaken to determine whether or not genetic factors contribute to risk for the occurrence of seizures with specific syndrome type being determined by genetic modifiers and/or environmental exposures or there are specific genes for epilepsy syndrome type. Methods: Information on history of seizures was obtained either by mailed questionnaire or telephone interview from 81,798 twins and their relatives included in three population-based twin registries located in Denmark, Norway and the United States. History of seizures was validated using medical records, where available, and by personal and/or parental interviews. Epilepsy syndrome type was determined by epileptologists who were blinded to family relationship on the basis of this information using the International League Against Epilepsy Classification System for Epilepsies and Epileptic Syndromes. The proportion of monozygotic twin pairs, dizygotic twin pairs and parent-offspring pairs who were concordant for epilepsy syndrome type among those concordant for verified history of seizures was determined. Results: A history of seizures was verified in 1,661 twins and 2,229 of their relatives. This included 129 monozygotic (MZ), 73 dizygotic (DZ) and 301 parent-offspring (PO) pairs in which both pair members had a history of seizures. Among pairs concordant for seizures, 88.4% (MZ), 62.5% (DZ) and 56.1% (PO) were concordant for epilepsy. The percentage of pairs concordant for seizures that are concordant for major epilepsy syndrome type (localization-related, generalized or undetermined) dropped to 72.1% (MZ), 35% (DZ) and 35% (PO). Conclusions: While syndrome specific genes may be responsible for the occurrence of epilepsy in some cases, the results of this study suggest that genes may also contribute to an overall susceptibility for seizures with epilepsy syndrome type being determined by genetic background modifiers and environmental exposures. [Supported by a grant from the National Institutes of Health NINDS (NS31564)].