Abstracts

Epilepsy and febrile seizures are complex disorders with both distinct and overlapping genetic influences. Febrile seizures are associated with an increased risk of epilepsy (individual comorbidity). In addition, each disorder aggregates in families, and an increased risk of each disorder has been reported in the relatives of probands with the other. No single study has comprehensively examined the contributions of shared and distinct genetic influences to these observations. We aimed to evaluate the overlapping genetic contributions to epilepsy and febrile seizures by studying patterns of co-occurrence, within individuals and within families, in a large genetic epidemiologic study., The study population comprised 2279 full siblings of 879 probands with epilepsy from the Epilepsy Family Study of Columbia University. Data on febrile seizures were obtained by interview of at least one of the proband[apos]s parents. We evaluated the risks of epilepsy in siblings without febrile seizures, and febrile seizures in siblings without epilepsy, in relation to the proband[apos]s febrile seizure history and family history of febrile seizures and epilepsy in other first-degree relatives. We considered four types of family history: epilepsy alone, febrile seizures alone, both epilepsy and febrile seizures, and neither. We used Cox proportional hazards models to compute rate ratios [RRs] and 95% confidence intervals [CI] for epilepsy, and logistic regression to compute odds ratios [ORs] for febrile seizures., Epilepsy risk in siblings was not associated with a history of febrile seizures in the proband (RR=0.5, CI 0.17-1.35). As expected, epilepsy risk was associated with a family history of epilepsy in other relatives (RR=3.6, CI 1.78-7.47). Epilepsy risk was not associated with a family history of febrile seizures alone (RR=1.4, CI 0.47-3.85), but was strongly associated with a family history of [italic]both[/italic] febrile seizures and epilepsy (RR=8.9, CI=3.92-20.05). The risk of febrile seizures in siblings was associated with a history of recurrent febrile seizures in the proband (OR=2.3, CI 1.17-4.60), but not with a history of a single febrile seizure in the proband. As expected, febrile seizure risk was associated with a family history of febrile seizures (OR=4.3, CI 2.54-7.39). Febrile seizure risk was also associated with a family history of epilepsy alone (OR=2.3, CI 0.99-5.16). As in the analysis of epilepsy, febrile seizure risk was strongly associated with a family history of both epilepsy and febrile seizures (OR=6.1, CI 2.46-15.18)., These results provide evidence for familial clustering of epilepsy and febrile seizures that is not attributed to individual comorbidity of the two disorders. Familial clustering was strongest in families containing multiple individuals with epilepsy. The findings are reminiscent of the syndrome GEFS+, which has previously been described only in highly selected pedigrees., (Supported by NIH R01 NS43472 and an Epilepsy Foundation predoctoral fellowship.)