Implications of Provider Specialty, Test Type, and Demographic Factors on Genetic Testing Outcomes for Patients with Autism Spectrum Disorder

Abstract

A minority of patients with autism spectrum disorder (ASD) are offered genetic testing by their providers or referred for genetics evaluation despite published guidelines and consensus statements supporting genetics-informed care for this population. This study aimed to investigate the ordering habits of providers of different specialties and to additionally assess the diagnostic utility of genetic testing by test type, patient sex, and race and ethnicity. We retrospectively analyzed data associated with orders for the indication of ASD from a large clinical laboratory over 6 years (2017-2022). Geneticists and neurologists were more likely than other specialists to order exome sequencing and neurodevelopmental (NDD) panel testing while other providers were more likely to order chromosomal microarray (CMA) and Fragile X testing. Exome had the highest diagnostic yield (24.5%), followed by NDD panel (6.4%), CMA (6.2%), and Fragile X testing (0.4%). Females were 1.4x (95% CI: 1.2-1.7) more likely than males to receive a genetic diagnosis. However, for Fragile X, males had a higher diagnostic yield than females (0.4% vs 0.2%). Our findings highlight the need to enable non-genetics providers to order comprehensive genetic testing or promote referral to genetics following negative CMA and/or Fragile X testing. Our data supports that ASD testing should include exome, CMA, and other clinically indicated tests, as first-tier tests, with the consideration of panel testing, in cases where exome sequencing is not an option. Lastly, our study helps to inform expectations for genetic testing yield by test type and patient presentation.

Keywords: Autism; Genetic testing; Genetics.