Identification of Undetected Monogenic Cardiovascular Disorders.

Journal Article (Journal Article)

BACKGROUND: Monogenic diseases are individually rare but collectively common, and are likely underdiagnosed. OBJECTIVES: The purpose of this study was to estimate the prevalence of monogenic cardiovascular diseases (MCVDs) and potentially missed diagnoses in a cardiovascular cohort. METHODS: Exomes from 8,574 individuals referred for cardiac catheterization were analyzed. Pathogenic/likely pathogenic (P/LP) variants associated with MCVD (cardiomyopathies, arrhythmias, connective tissue disorders, and familial hypercholesterolemia were identified. Electronic health records (EHRs) were reviewed for individuals harboring P/LP variants who were predicted to develop disease (G+). G+ individuals who did not have a documented relevant diagnosis were classified into groups of whether they may represent missed diagnoses (unknown, unlikely, possible, probable, or definite) based on relevant diagnostic criteria/features for that disease. RESULTS: In total, 159 P/LP variants were identified; 2,361 individuals harbored at least 1 P/LP variant, of whom 389 G+ individuals (4.5% of total cohort) were predicted to have at least 1 MCVD. EHR review of 342 G+ individuals predicted to have 1 MCVD with sufficient EHR data revealed that 52 had been given the relevant clinical diagnosis. The remaining 290 individuals were classified as potentially having an MCVD as follows: 193 unlikely (66.6%), 50 possible (17.2%), 30 probable (10.3%), and 17 definite (5.9%). Grouping possible, probable, definite, and known diagnoses, 149 were considered to have an MCVD. Novel MCVD pathogenic variants were identified in 16 individuals. CONCLUSIONS: Overall, 149 individuals (1.7% of cohort) had MCVDs, but only 35% were diagnosed. These patients represents a "missed opportunity," which could be addressed by greater use of genetic testing of patients seen by cardiologists.

Full Text

Duke Authors

Cited Authors

  • Abdulrahim, JW; Kwee, LC; Alenezi, F; Sun, AY; Baras, A; Ajayi, TA; Henao, R; Holley, CL; McGarrah, RW; Daubert, JP; Truby, LK; Vemulapalli, S; Wang, A; Khouri, MG; Shah, SH

Published Date

  • August 18, 2020

Published In

Volume / Issue

  • 76 / 7

Start / End Page

  • 797 - 808

PubMed ID

  • 32792077

Pubmed Central ID

  • PMC7428466

Electronic International Standard Serial Number (EISSN)

  • 1558-3597

Digital Object Identifier (DOI)

  • 10.1016/j.jacc.2020.06.037


  • eng

Conference Location

  • United States