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Identification of Undetected Monogenic Cardiovascular Disorders.

Publication ,  Journal Article
Abdulrahim, JW; Kwee, LC; Alenezi, F; Sun, AY; Baras, A; Ajayi, TA; Henao, R; Holley, CL; McGarrah, RW; Daubert, JP; Truby, LK; Vemulapalli, S ...
Published in: J Am Coll Cardiol
August 18, 2020

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.

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Published In

J Am Coll Cardiol

DOI

EISSN

1558-3597

Publication Date

August 18, 2020

Volume

76

Issue

7

Start / End Page

797 / 808

Location

United States

Related Subject Headings

  • alpha-Glucosidases
  • United States
  • Sequence Deletion
  • Prevalence
  • Missed Diagnosis
  • Middle Aged
  • Male
  • Humans
  • Hemochromatosis Protein
  • Genomic Structural Variation
 

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Abdulrahim, J. W., Kwee, L. C., Alenezi, F., Sun, A. Y., Baras, A., Ajayi, T. A., … Shah, S. H. (2020). Identification of Undetected Monogenic Cardiovascular Disorders. J Am Coll Cardiol, 76(7), 797–808. https://doi.org/10.1016/j.jacc.2020.06.037
Abdulrahim, Jawan W., Lydia Coulter Kwee, Fawaz Alenezi, Albert Y. Sun, Aris Baras, Teminioluwa A. Ajayi, Ricardo Henao, et al. “Identification of Undetected Monogenic Cardiovascular Disorders.J Am Coll Cardiol 76, no. 7 (August 18, 2020): 797–808. https://doi.org/10.1016/j.jacc.2020.06.037.
Abdulrahim JW, Kwee LC, Alenezi F, Sun AY, Baras A, Ajayi TA, et al. Identification of Undetected Monogenic Cardiovascular Disorders. J Am Coll Cardiol. 2020 Aug 18;76(7):797–808.
Abdulrahim, Jawan W., et al. “Identification of Undetected Monogenic Cardiovascular Disorders.J Am Coll Cardiol, vol. 76, no. 7, Aug. 2020, pp. 797–808. Pubmed, doi:10.1016/j.jacc.2020.06.037.
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. Identification of Undetected Monogenic Cardiovascular Disorders. J Am Coll Cardiol. 2020 Aug 18;76(7):797–808.
Journal cover image

Published In

J Am Coll Cardiol

DOI

EISSN

1558-3597

Publication Date

August 18, 2020

Volume

76

Issue

7

Start / End Page

797 / 808

Location

United States

Related Subject Headings

  • alpha-Glucosidases
  • United States
  • Sequence Deletion
  • Prevalence
  • Missed Diagnosis
  • Middle Aged
  • Male
  • Humans
  • Hemochromatosis Protein
  • Genomic Structural Variation