Abstracts

Rationale: Although numerous studies have shown a history of complex febrile seizures (FS) will increase the risk of epilepsy, the role of genetic factors is unclear. Previous studies have suggested that a significant family history of febrile seizures may not be a risk factor for developing epilepsy. This study was carried out to evaluate the genetic epidemiology of FS in a large cohort ascertained from three large population-based twin registries.Methods: Information on history of seizures was obtained either by mailed questionnaire or telephone interview from 81, 798 twins included in three population-based twin registries located in Denmark, Norway and the United States. Seizures were validated by personal and/or parental interviews, and medical records when available. FS type was classified by epileptologists to distinguish simple or complex (including status epilepticus) FS. The proportion of twins with FS classified by type, who later developed epilepsy, was determined. Results: Histories of FS were validated in 1049 twins in 899 pairs. Of these, 2.5% (16/641) with a history of simple FS alone, 11.3% (14/124) with a history of complex FS and 22.2% (16/72) of those with at least one episode of febrile status epilepticus went on to develop epilepsy. The percentage of those who developed epilepsy whose FS type could not be classified was 14.2% (20/211). In 40.6% of the 97 twin pairs where one pair member had a FS and went on to have epilepsy, a history of seizures was also verified in the cotwin. This included 17/24 (70.8%) monozygotic pairs and 10/41 (24.4%) dizygotic pairs. Among individuals that developed epilepsy after FS, 21.1% had only simple FS, 18.4% had complex FS (without status epilepticus) and 21.1% had febrile status epilepticus. Conclusions: These results are consistent with previous findings regarding the association between FS and the later risk for epilepsy. This is not limited to FS semiology. The increased frequency of seizures in the cotwin of monozygotic pairs with FS who went on to develop epilepsy suggests that genetic factors may play a significant role in its later development. Whether these families represent patients with GEFS+ or other known syndromes are presently unclear and requires further clinical and molecular evaluation.