Febrile Seizures and Epilepsy: Association With Autism and Other Neurodevelopmental Disorders in the Child and Adolescent Twin Study in Sweden

BACKGROUND: There is a recently well-documented association between childhood epilepsy and early symptomatic syndromes eliciting neurodevelopmental clinical examinations (ESSENCE) including autism spectrum disorder, but the relationship between febrile seizures and ESSENCE is less clear. METHODS: The Child and Adolescent Twin Study in Sweden (CATSS) is an ongoing population-based study targeting twins born in Sweden since July 1, 1992. Parents, of 27,092 twins were interviewed using a validated DSM-IV-based interview for ESSENCE, in connection with the twins' ninth or twelfth birthday. Diagnoses of febrile seizures (n = 492) and epilepsy (n = 282) were based on data from the Swedish National Patient Register. Prevalence of ESSENCE in individuals with febrile seizures and epilepsy was compared with prevalence in the twin population without seizures. The association between febrile seizures and ESSENCE was considered before and after adjustment for epilepsy. Age of diagnosis of febrile seizures and epilepsy was considered as a possible correlate of ESSENCE in febrile seizures and epilepsy. RESULTS: The rate of ESSENCE in febrile seizures and epilepsy was significantly higher than in the total population without seizures (all P < 0.001). After adjusting for epilepsy, a significant association between febrile seizures and autism spectrum disorder, developmental coordination disorder, and intellectual disability remained. Earlier age of onset was associated with all ESSENCE except attention-deficit/hyperactivity disorder in epilepsy but not with ESSENCE in febrile seizures. CONCLUSIONS: In a nationally representative sample of twins, there was an increased rate of ESSENCE in childhood epilepsy and in febrile seizures. Febrile seizures alone could occur as a marker for a broader ESSENCE phenotype.