Epidemiological and clinical studies show that children with autism have a ten-fold higher risk of epilepsy compared with the general population. In addition, most mouse models of autism display spontaneous epileptic tendencies, altered brain activity or synaptic deficits. The disrupted genes in mouse models of autism include BCKDK, CNTNAP2, FMR1, SYN1, CDKL5 and SCN1A. Joseph Gleeson and his colleagues at the University of California, San Diego and The Rockefeller University are studying the genetic basis of the connection between autism and epilepsy in order to gain insight into the mechanisms of these diseases, which may point to more targeted therapies.
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Gleeson leads a worldwide, multi-year recruitment effort that has resulted in the Simons Recessive Autism Cohort, now consisting of 103 families, most with two or more children affected by both autism and epilepsy. One special feature of this cohort is that most families are from the Middle East, which traditionally has a high rate of intermarriage among cousins. This greatly facilitates the identification of key genes linked to autism and epilepsy in the families.

Gleeson’s team has also recruited a second cohort of 400 children in the U.S. with both autism and epilepsy to validate findings from the Middle East. Key in both recruitments is a diagnosis of an autism spectrum disorder that predated epilepsy onset, to ensure that the epilepsy did not lead secondarily to the autism features. The researchers plan to use exome sequencing — the sequencing of protein-coding regions of the genome — to identify mutations.

Gleeson expects to find the same altered genes in the Middle Eastern and U.S. cohorts. Preliminary results already point to potential new causes and treatments for autism and epilepsy. His team is also exploring whether some forms of autism and other neurodevelopmental conditions respond to treatment with natural dietary supplementation.