TY - JOUR
T1 - Identification of Undetected Monogenic Cardiovascular Disorders
AU - Abdulrahim, Jawan W.
AU - Kwee, Lydia Coulter
AU - Alenezi, Fawaz
AU - Sun, Albert Y.
AU - Baras, Aris
AU - Ajayi, Teminioluwa A.
AU - Henao, Ricardo
AU - Holley, Christopher L.
AU - McGarrah, Robert W.
AU - Daubert, James P.
AU - Truby, Lauren K.
AU - Vemulapalli, Sreekanth
AU - Wang, Andrew
AU - Khouri, Michel G.
AU - Shah, Svati H.
N1 - Generated from Scopus record by KAUST IRTS on 2023-02-15
PY - 2020/8/18
Y1 - 2020/8/18
N2 - 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.
AB - 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.
UR - https://linkinghub.elsevier.com/retrieve/pii/S0735109720357338
UR - http://www.scopus.com/inward/record.url?scp=85088969495&partnerID=8YFLogxK
U2 - 10.1016/j.jacc.2020.06.037
DO - 10.1016/j.jacc.2020.06.037
M3 - Article
SN - 1558-3597
VL - 76
SP - 797
EP - 808
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 7
ER -