Abstracts

Rationale: Infantile spasms (IS) is an often catastrophic epilepsy syndrome characterized by epileptic spasms, hypsarrhythmia, and developmental impairment. Other forms of epilepsy, as well as autism spectrum disorder (ASD) are frequently comorbid among children with IS. Although there is known shared genetic susceptibility among these disorders (e.g. trisomy 21, tuberous sclerosis complex), the full extent of genetic overlap is known. Conversely, it has been hypothesized that IS may play a causative role in the development of subsequent epilepsy and ASD. Using a large cohort of children with IS, we set out to explore the risk of IS, epilepsy, and ASD among siblings of children with IS, as a function of putative etiology. Methods: We conducted a retrospective cohort study using a large clinical database that includes all children with video-EEG confirmed infantile spasms. Using the electronic medical record, we identified all children with IS at our center who had at least one sibling. For each index IS patient, we recorded the putative etiology, genetic testing results, and sibling medical history. We report the estimated the risk of IS, other epilepsy, and ASD in siblings as a percentage with poisson-derived 95% confidence intervals (95%CI). Results: We screened 475 screened patients and found 294 (62%) with at least one sibling. One patient (0.3%, 95%CI upper limit 1.9%) had a sibling with IS. Five (1.7%, 95%CI upper limit 4.0%) patients had a sibling with another form of epilepsy (2.0%, 95%CI upper limit 4.0%). Six (2.0%, 95%CI upper limit 4.4%) patients had a sibling with ASD. Siblings with IS, other epilepsy, and/or ASD were not restricted to the subset of IS patients with unknown etiology. Conclusions: Although the rates of IS, other epilepsy, and ASD among siblings in this cohort are higher than prevalence rates in the general population, they are still relatively low. In particular, sibling concordance for ASD is especially low. This suggests that (1) there is a limited degree of shared genetic predisposition, (2) the relatively high risk of ASD among children with history of IS may be mediated by the IS itself, and (3) ASD risk may be potentially modifiable by treatment. These data provide some limited guidance to parents of children with IS who seek to estimate the risk of IS, epilepsy, and ASD in a subsequent child. These findings warrant replication and more rigorous further study. Funding: This study was accomplished with support from the Elsie and Isaac Fogelman Endowment, the Hughes Family Foundation, and the UCLA Children's Discovery and Innovation Institute