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

Area of Science:

• Medical Genetics
• Developmental Pediatrics
• Genomic Medicine

Background:

• Nonsyndromic neurodevelopmental disabilities, including autism spectrum disorder and global developmental delay/intellectual developmental disability, often require genetic testing for diagnosis.
• Access to exome sequencing (ES) is limited for these patients, particularly when relying solely on genetics referrals.
• Nongenetics subspecialties can play a role in increasing access to diagnostic genetic testing.

Purpose of the Study:

• To assess the feasibility of developmental-behavioral pediatricians offering exome sequencing (ES) to patients with nonsyndromic neurodevelopmental disabilities.
• To identify barriers and facilitators to ES completion in this patient population.
• To evaluate the diagnostic yield of ES when ordered by a nongenetics subspecialist.

Main Methods:

• Retrospective chart review of a feasibility study involving 136 patients.
• Exome sequencing (ES) offered by developmental-behavioral pediatricians at a single site.
• Analysis of test completion rates, dropout reasons, and diagnostic yield.

Main Results:

• 110 out of 136 patients pursued ES; 54.5% completed testing over 22 months.
• The primary dropout point was pretest genetic counseling (29.1%), with cost being a cited factor.
• The diagnostic yield for ES was 20%, with 16.7% of reports showing variants of uncertain significance.

Conclusions:

• Relying solely on genetics referrals presents barriers to exome sequencing (ES) access.
• Expanding ES ordering to nongenetics subspecialists, like developmental-behavioral pediatricians, can increase patient access to molecular diagnoses.
• This model offers an effective pathway for earlier diagnosis, though further research on barriers and replication in other specialties is warranted.