Clinical and genetic analysis of children with a dual diagnosis of Tourette syndrome and autism spectrum disorder.

Gilles de la Tourette Syndrome (TS) is a neurodevelopmental disorder that causes children to make repeated, brief involuntary movements or sounds. TS can be co-morbid with other neurodevelopmental disorders, including autism spectrum disorder (ASD). Clusters of biologically related genes have been associated with neurodevelopmental disorders, suggesting shared pathologies. However, the genetic contribution to TS remains poorly defined. We asked whether children with both TS and ASD differed clinically from children with ASD alone, and identified potentially deleterious genetic events in children with TS and ASD. We compared clinical data from 119 children with ASD and TS to 2603 children with ASD, all from the Simons Simplex Collection. We performed gene set enrichment analysis on de novo genetic events in children with both TS and ASD to identify candidate genes and pathways, and compared these genes and pathways with those previously identified in TS. Children with TS and ASD were diagnosed at an older age, had higher IQ scores, and had more restricted and repetitive behavior than children with ASD but not TS. Gene Ontology analysis revealed that proteins important for specific biological pathways, including regulation of calcium ion-dependent exocytosis, basement membrane organization, and visual behavior and learning, and specific cellular pathways, including basal lamina and ciliary transition zone, are enriched among genes with de novo mutations in children with TS and ASD. Clinical and genetic analysis of cohorts of affected children can help to determine the underlying pathophysiology of TS and other neurodevelopmental disorders.