Males are four to five times more likely to have autism than are females. This powerful observation implies not only that males are at greater risk, but that there may be real differences in the expression of autism between males and females. Thomas Frazier at the Cleveland Clinic Foundation and his collaborator Antonio Hardan at Stanford University in California used the Simons Simplex Collection to compare males and females with autism across a range of clinical measures. The collection is a repository of genetic samples from families that have one child with autism and unaffected parents and siblings.

They found that females with autism tend to have greater impairments in social communication, poorer daily living skills and more irritability, but less restriction of interests relative to males with autism.

That females with autism have less restriction of interests is important because it suggests either that they are under-captured in the diagnostic process or that there are real differences in the prevalence of restricted interests that may be driven by sex differences in biology or early learning.

Frazier and his group also found no evidence of sex-specific thresholds for autism, whereby girls with autism require additional disease burden to cross the diagnostic threshold. Instead, siblings and parents from families that have a girl with autism do not substantively differ from siblings and parents from families that have one or more boys with autism. The latter result implies that, at least in single-incidence families, powerful spontaneous, or de novo, variation is a primary driver of autism in both girls and boys.