Abstracts

Genetic factors have long been recognized as important determinants of risk for febrile seizures. Significant strides have been made towards an understanding of the factors that impact upon their risk of occurrence and the risk that a febrile seizure, if it does occur, will be greatly prolonged. However, the specific factors involved in determining risk for prolonged febrile seizures or febrile status epilepticus (FSE) remain to be identified. This study was undertaken to determine whether or not genetic factors contribute to risk for the occurrence of FSE. The occurrence of FSE was determined in 13,506 unselected Virginia-born twin pairs who were ascertained from birth records and members of their families. Information on seizure history was obtained either by mailed questionnaire or telephone interview. History of FSE was validated using medical records, where available, and by personal and/or parental interviews. Concordance-rate analyses were used to assess the contribution of genetic factors to FSE risk. The frequency of FSE among first degree relatives of FSE probands was also determined. Among 416 twins and 526 relatives with a verified history of seizures, febrile seizures (FS) were validated in 173 twins and 183 relatives. FSE was verified in 40 individuals included in 30 families. This included 22 twins in 21 (5 monozygotic (MZ) and 16 dizygotic (DZ)) twin pairs. The single FSE concordant pair was MZ. Probandwise concordance rates for FSE in this sample were 0.33 (95% CI: 0.43-0.777) for MZ and 0.00 for DZ twins. Analyses of the distribution of FSE, FS and epilepsy among the relatives of both twin and non-twin FSE probands included in this sample found FSE in 5% of siblings of FSE probands, 6% of probands[apos] offspring, 6% of their mothers and none of their fathers. Neither FSE, FS or epilepsy were found to have occurred in any of the fathers of the probands included in the families identified. The probandwise concordance rate estimate obtained for MZ twins is consistent with the existence of a contribution of genetic factors to risk for the occurrence of FSE. This, along with the increased frequency of FSE (5% or greater) observed among first degree relatives of FSE probands as compared to the 0.1% - 0.25% frequency of FSE observed in the general population, suggests that genetic factors do contribute to FSE risk. (Supported by Grants from the National Institutes of Health NINDS (NS25630 and NS31564).)