‘‘Autism spectrum disorders’’(ASDs) are a heterogeneous and common group of developmental disorders. Affected infants and children demonstrate severe and persistent impairments in expressive and receptive language and social interaction skills that are evident before age 3, and a restricted range of interests and stereotypic behaviors. The Centers for Disease Control now estimates the prevalence of ASDs (including autism, Asperger syndrome, and pervasive developmental delay not otherwise specified (PDD-NOS)) as approximately 5.6 per 1,000 children within the United States [MMWR, 2006]. Although the causes of most ASD cases are currently unknown, there are many scientific studies that demonstrate strong heritability and genetic components to the causes of autism. These include familial aggregation and increased recurrence risks for siblings (2–8%, 10–60 times the general population risk); twin studies with concordance in monozygotic twins of 60–90% and of 0–10% in dizygotic twins; and a sex preference, with a male/female ratio of 3–4: 1 [Muhle et al., 2004; Spence, 2004; Wassink et al., 2004; MMWR, 2006]. There are several single gene disorders (eg, fragile X syndrome, Rett syndrome, untreated PKU, and tuberous sclerosis) and chromosome abnormalities (duplication of 15q11 containing the Prader–Willi/Angelman region) in which autistic manifestations are prominent and common [reviewed in Cohen et al., 2005]. However, known genetic causes account for 10% of cases. It is estimated that 3–15 to> 100 genes, in addition to environmental effects, contribute to ‘‘disease’’susceptibility.

Several large collaborative studies in the United States and other countries are ongoing with goals of identifying these genes [Geschwind et al., 2001; IMGSAC, 2001; Cantor et al., 2005; McCauley et al., 2005; Ylisaukko-Oja et al., 2006], although results, to date, have been disappointing and/or inconclusive. Such research has been hampered, in part, by a lack of comprehensive clinical phenotyping or performance of appropriate and comprehensive genetic testing of affected individuals to rule out known causes.