Motor stereotypies, a core feature of autism, are involuntary, repetitive movements that are often associated with self-injury. Treatments for these behaviors are limited and often inadequate, owing to a poor understanding of the underlying biological mechanisms.

Thomas V. Fernandez and his colleagues at the Yale Child Study Center aim to clarify the causes of motor stereotypies by studying a rare group of individuals showing stereotypic behaviors in the absence of social or intellectual disability. Researchers at Johns Hopkins University in Baltimore identified and evaluated 100 mother-father-child trios in which the child has complex motor stereotypies and no evidence of developmental neuropsychiatric disorders. By sequencing all coding regions, or exomes, of these individuals and analyzing submicroscopic variations in chromosomal structure in individuals with these stereotypies and their unaffected parents, the investigators aim to discover rare mutations contributing to the risk for such behaviors.

Fernandez and his colleagues plan to first test whether spontaneous mutations in the DNA sequence or large variations in gene copy number are found at a higher rate in affected individuals than in controls. In addition, they plan to study select families with many affected individuals in search of rare mutations that co-occur with stereotypies in multiple generations. They can then begin to search for biological networks that are enriched among the genes disrupted by all of the identified spontaneous, or de novo, mutations. Finally, the researchers plan to evaluate the strongest candidate genes and regions in the Simons Simplex Collection, a database of genetic and clinical information from families that include one child with autism and unaffected parents and siblings, to determine whether genetic risk for the stereotypies is also found in individuals with social deficits.