Date of Award

Spring 2020

Document Type

Open Access Thesis


Genetic Counseling

First Advisor

Kellie Walden


The purpose of this study is to evaluate the diagnostic utility of whole exome sequencing (WES) in patients with intellectual disability (ID) or developmental delay (DD), and to determine which patients may be the best candidates for WES as a first-tier diagnostic test. The diagnostic and clinical utility of WES has emerged to be greater than that of karyotype and chromosomal microarray for patients with ID or DD of unknown etiology, which are currently recommended as first-tier diagnostic tests for these patients. The emergence of next generation sequencing has led to more rapid identification of rare and novel genetic disorders. Diagnosis of such disorders can impact medical management and save money. The value of this study lies in identifying which patients with ID or DD are more likely to receive a diagnosis via WES and therefore should be offered WES as a first-tier diagnostic test. This study is a retrospective review of electronic medical records of patients with ID/DD seen at the Greenwood Genetic Center (GGC) who have had WES. Patients were categorized into diagnosed, undiagnosed, or uncertain categories. Comparisons between patients were made based on delay types, dysmorphic features, birth defects, and comorbid conditions. Neither delay type, number of delays, age of diagnosis, or birth defects had a significant effect on likelihood of diagnosis. Patients with neurological features, tone differences, or eye movement disorders were significantly more likely to obtain a diagnosis by WES. Changes to medical management in diagnosed patients include referrals to new specialists, adjustments in medication v prescriptions, identification of contraindicated medications, and referrals to specialty clinics specific to disease. These data suggest that WES should be considered as a first-tier test in any patient with ID or DD, and WES may have a higher diagnostic utility for those with underlying neurological disorders.