Abstracts

Epilepsy and febrile seizures have been found to co-occur both in individuals and in families, but the genetic relationship between the two disorders is not well understood. We evaluated the hypothesis of a shared genetic susceptibility to epilepsy and febrile seizures. Adults with epilepsy from the Epilepsy Family Study of Columbia University were examined for history of febrile seizures according to epilepsy type (idiopathic generalized [IGE, n=100], cryptogenic localization-related [LRE, n=604], and postnatal symptomatic [SE, n=151]), and family history of epilepsy and/or febrile seizures. To ensure the validity of data on febrile seizures, subjects were included only if a parent was interviewed. Previous analyses of these data showed that subjects with epilepsies attributed to identified postnatal risk factors (SE) did not have an increased frequency of a family history of epilepsy. Thus, under a model of shared genetic influence on epilepsy and febrile seizures, we hypothesized that: (1) prevalence of a febrile seizure history would be increased in subjects with IGE or LRE (i.e., of unknown, potentially genetic, etiology), but not in those with SE, and (2) a family history of idiopathic or cryptogenic epilepsy would be more common in subjects with febrile seizures than in those without. Logistic regression was used to calculate bivariate and multivariate odds ratios (OR) and 95% confidence intervals (CI). Prevalence of a febrile seizure history was increased in all three subject groups, compared with rates of 2-5% in the population (IGE 12.0%, LRE 19.9%, SE 15.2%). Although the three groups did not differ significantly, LRE cases were twice as likely as those with IGE to have had a febrile seizure (OR 1.8, 95% CI 0.96-3.43), after controlling for potential confounders. A family history of febrile seizures was associated with a febrile seizure history (as expected from the independent genetic influence on febrile seizures). However, a family history of [italic]epilepsy[/italic] was not associated with a febrile seizure history, either overall or within any subject group. Further analyses revealed differences among the three subject groups in the predictors of febrile seizure occurrence, age at onset, and recurrence. These findings do not support the hypothesis of a shared genetic susceptibility to epilepsy and febrile seizures for the majority of cases. We found a strong association between febrile seizures and all types of epilepsy, including those presumed to be caused by identified environmental factors occurring after the febrile seizures. The predictors of a febrile seizure history differed among subjects with IGE, LRE, and SE, suggesting that the causal pathways underlying the association between febrile seizures and epilepsy may differ among these three groups. (Supported by NIH grants R01 NS43472 and R01 NS36319, and an Epilepsy Foundation predoctoral fellowship.)