To determine the utility of genetic testing for patients with autism spectrum disorders (ASD) and/or intellectual disability (ID)

Autism spectrum disorders and ID are common and frequently co-morbid disorders with a high degree of genetic heterogeneity.  Exome sequencing was reported to have a positive diagnostic result (PDR) of ~14-33% for ASD/ID cohorts.  However, studies demonstrating the utility of genetic testing for subgroups of patients within this wide phenotypic spectrum are rare.

This is a retrospective study of genetic testing results of 2,497 patients with ASD/ID/developmental delay referred to our clinical laboratory.  For each of these patients, 2,300+ genes associated with ASD and/or ID were sequenced and analyzed. 

The PDR for all cases was 15.7%; however, the PDR varied depending on the clinical information provided. Patients with ID and multiple additional malformations or other significant medical issues, but not autistic features, had the highest PDR (~34%, 44/128), whereas patients with autistic features and multiple additional medical issues in the absence of ID had a significantly lower PDR (14.5%, 56/386, p<0.0001).  Patients with isolated ID or ASD had a PDR of ~18% (8/44) and ~4% (19/492), respectively. The PDR for patients <2 years old with developmental delays was ~27% (27/99). High genetic heterogeneity was observed among positive cases. However, 26 different genes were responsible for >40% of positive cases. 

Genetic testing for patients with ID and additional major medical issues revealed a genetic etiology of disease in almost one-third of cases.  However, a genetic etiology was less likely to be identified in patients with ASD.  The presence of additional phenotypic findings did correlate with an increased PDR.  Although there is vast genetic heterogeneity for ID, findings in just 26 genes accounted for a significant portion of positive cases, suggesting a minimum number of genes that should be tested for these patients.