Mutation type is not clinically useful in predicting prognosis in hypertrophic cardiomyopathy.

Journal Article (Journal Article;Review)

Hypertrophic cardiomyopathy (HCM), or clinically unexplained hypertrophy of the heart, is a common genetic cardiovascular disorder marked by genetic and phenotypic heterogeneity. As the genetic mutations underlying the pathogenesis of this disease have been identified, investigators have attempted to link mutations to clearly defined alterations in survival in hopes of identifying prognostically relevant biomarkers of disease. While initial studies labeling particular MYH7-encoded beta myosin heavy chain and TNNT2-encoded cardiac troponin T mutations as “malignant” or “benign” raised hopes for mutation-specific risk stratification in HCM, a series of subsequent investigations identified mutations in families with contradictory disease phenotypes. Furthermore, subsequent proband-based cohort studies indicated that the clinical prognostic relevance of individual mutations labeled as “malignant” or “benign” in large referral centers is negligible. Herein, we seek to summarize the controversy and dispute the notion that mutation-specific risk stratification in HCM is possible at the present time. We provide evidence for clinicians and basic scientists alike to move beyond simple mutation descriptors to a more nuanced understanding of HCM mutations that fully captures the multi-factorial nature of HCM disease expression.

Full Text

Duke Authors

Cited Authors

  • Landstrom, AP; Ackerman, MJ

Published Date

  • December 7, 2010

Published In

Volume / Issue

  • 122 / 23

Start / End Page

  • 2441 - 2449

PubMed ID

  • 21135372

Pubmed Central ID

  • PMC6309993

Electronic International Standard Serial Number (EISSN)

  • 1524-4539

Digital Object Identifier (DOI)

  • 10.1161/CIRCULATIONAHA.110.954446


  • eng

Conference Location

  • United States