Diagnostic yield in the clinical genetic evaluation of autism spectrum disorders

Purpose: Clinical geneticists are often asked to evaluate patients with autism spectrum disorders (ASDs) in reference to questions about cause and recurrence risk. Recent advances in diagnostic testing technology have greatly increased the options available to them. It is not currently clear what the overall diagnostic yield of a battery of tests, either collectively or individually, might be. The purpose of this study was to evaluate the diagnostic yield of a stepwise approach we have implemented in our clinics. Methods: We used a three-tiered neurogenetic evaluation scheme designed to determine the cause of ASDs in patients referred for clinical genetic consultation. We reviewed the results of our diagnostic evaluations on all patients referred with a confirmed diagnosis of autism over a 3-year period. Results: By using this approach, we found an overall diagnostic yield for ASDs of more than 40%. This represents a significant increase in the diagnostic yield reported just a few years ago. Conclusions: Given the implications of these diagnoses on recurrence risk and associated medical conditions, a targeted neurogenetic evaluation of all persons with ASDs seems warranted. We discuss the issues in the future implementation of a fourth tier to the evaluation with the potential for an even higher diagnostic yield.