Feasibility Pilot to Expand Exome Sequencing Access for Children With Nonsyndromic Neurodevelopmental Disorders

To illustrate a pathway for nongenetics subspecialties to increase access to exome sequencing (ES) for patients with nonsyndromic neurodevelopmental disabilities of autism spectrum disorder and/or global developmental delay/intellectual developmental disability, by reporting the results of a single site feasibility study.

Retrospective chart review, feasibility study of 136 patients with nonsyndromic neurodevelopmental disabilities offered ES by a developmental-behavioral pediatricians at a single site.

In a time span of 22 months, 110 patients chose to pursue ES and 54.5% of those completed testing. The most common dropout point was the pretest genetic counseling step (29.1%). Cost was cited by 7/15 families who provided information regarding noncompletion. Insurance type, race/ethnicity, language, or underlying diagnosis for ES were not significantly tied to test completion. The diagnostic yield was 20%, consistent with values reported for subpopulations of nonsyndromic patients, and the rate of variant of uncertain significance-only reports was 16.7%.

Existing literature and our current study suggest that relying solely on genetics referrals may not overcome existing barriers to accessing ES. Expanding the number and types of physicians ordering ES could enable more patients to access a molecular diagnosis earlier in their diagnostic journey. Our findings suggest that expanded ordering of ES by nongenetics subspecialists may be an effective and efficient method to offer appropriate diagnostic testing for patients for whom the specialist can leverage their medical expertise, despite study limitations (i.e., single-site design, modest sample size). Further research should investigate barriers for families who did not complete testing and replicate this model in other subspecialties.