Syndromic Autism Revisited: Review of the Literature and Lessons Learned

Autism spectrum disorder is a neurodevelopmental disorder characterized by deficits in communication, stereotyped behaviors, restricted interests, and impaired social skills. The severity of the neurobehavioral phenotype is variable and historically has been distinguished based on the presence or absence of additional symptoms, termed syndromic and nonsyndromic or idiopathic autism, respectively. However, although the advancement in genetic molecular technologies has brought an increased understanding of the pathophysiology of autism, most of this success has been in the diagnosis of syndromic disease, whereas the etiology of nonsyndromic autism remains less understood. Here we review the common and rare genetic syndromes that feature autism, specifically highlighting deletion and duplication syndromes, chromosomal anomalies, and monogenic disorders. We show that the study of syndromic autism provides insight into the phenotypic and molecular heterogeneity of neurodevelopmental disease and suggests how study of these disorders can be helpful in understanding disease mechanisms implicated in nonsyndromic autism.