Date of Award


Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)



First Advisor

Saquib A. Lakhani


Background: The boom of next generation DNA sequencing over the past decade has improved our ability to provide accurate genetic diagnoses for children with previously undiagnosed diseases, in turn leading to important advances in management and prognostication. Even given this progress, two areas of ongoing need are the accurate definition of further novel genetic diseases and to make genetic expertise and diagnostics widely available to children and families who have frequently endured grueling diagnostic odysseys. The Pediatric Genomics Discovery Program (PGDP) at Yale is an advanced genomics program focusing on both these areas, enrolling over 700 patients since its inception and eventually providing approximately one-third with new genetic diagnoses. Despite this success, we questioned whether the PGDP was achieving its full potential for impact by reaching a broad, representative participant population. Hypothesis: Current PGDP participant demographics are not representative of the racial/ethnic and socioeconomic diversity in the community of patients with potentially undiagnosed genetic diseases, which may relate to systemic barriers along the diagnostic odyssey. Methods: We created a questionnaire and in-depth interview process for existing PGDP participants to evaluate barriers to diagnostic care, then analyzed transcripts for themes. We analyzed demographic characteristics and referral routes of the PGDP cohort to find factors related to recruitment. We developed a screening tool based on diagnostic codes and queried the Yale New Haven Health System (YNHHS) electronic health record (EHR) to identify inpatient children between 2017-2022 with potentially undiagnosed genetic conditions, estimate their prevalence, and compare their characteristics with those already enrolled in PGDP. Then, we manually reviewed patient charts further narrow patients down to those who likely had undiagnosed genetic diseases. We used Pearson chi-square for categorical data, a multinomial regression model for predictors of enrollment, and Kruskal-Wallis one-way analysis of variance with pairwise comparisons with Bonferroni correction for multiple comparisons. Results: Survey results noted 1) Not knowing the PGDP existed (42%) and 2) Not knowing if they qualified for PGDP (36%) as the most common barriers to participant enrollment. Qualitative interviews identified three overarching themes related to the search for a unifying medical diagnosis for patients and families: 1) Challenges along the diagnostic odyssey (largely barriers in the healthcare system), 2) Tools to navigate the uncertainty (particularly parent serving as a care-captain) and 3) Perceptions of the PGDP (having reservations about participating vs desire for a diagnosis). In the PGDP cohort analysis, being directly identified by a PGDP-affiliated physician was associated with the highest representation of URM (52%) compared to referrals through Yale Genetics (27%) or Other Referrals (16%), and a significantly greater URM representation compared to both the national pediatric population (p=0.008) and to a peer genetics program (p


This is an Open Access Thesis.

Open Access

This Article is Open Access