Related Experiment Video

Updated: May 22, 2026

Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
03:45

Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model

Published on: August 8, 2022

Genotype-Phenotype Discordance in Cardiomyopathies: Pathophysiology, Clinical Expression, and Therapeutic

Abubakar Nazir1,2, Atif Hussain Sarwar3, Rameen Nazar4

  • 1Department of Internal Medicine The Jewish Hospital-Mercy Health Ohio USA.

Health Science Reports
|May 21, 2026
PubMed

Insights

Genotype-phenotype discordance in cardiomyopathies, where genetic results don't match clinical presentation, is complex. Understanding factors like epigenetics and environment is key for better diagnosis and treatment of these heart muscle disorders.

Area of Science:

  • Cardiovascular Genetics
  • Genomic Medicine
  • Translational Cardiology

Background:

  • Cardiomyopathies are myocardial disorders frequently linked to genetic mutations.
  • Genotype-phenotype discordance presents significant challenges in diagnosis, prognosis, and treatment.

Purpose of the Study:

  • To review mechanisms of genotype-phenotype discordance in cardiomyopathies.
  • To explore clinical implications and propose future research directions.
  • To bridge the gap between genetic findings and patient outcomes.

Main Methods:

  • Conducted a narrative review of literature from 2000-2025 using PubMed, Scopus, and Embase.
  • Searched for terms including "genotype-phenotype discordance", "cardiomyopathy", "penetrance", "expressivity", "modifier genes", and "epigenetics".
  • Prioritized studies on genetic/clinical variability, penetrance, expressivity, epigenetics, polygenic, and environmental factors.

Main Results:

  • Multiple factors cause discordance: incomplete penetrance, variable expressivity, epigenetics, modifier genes, and environmental influences (exercise, comorbidities).
  • Discordance complicates risk stratification and personalized therapy, leading to asymptomatic carriers or unexplained disease.
  • Emerging tools like polygenic risk scores and multi-omics integration aid phenotype prediction.

Conclusions:

  • Genotype-phenotype discordance highlights the complexity of translating genetic data into clinical practice for cardiomyopathies.
  • A multidimensional approach (genetic, molecular, environmental) is crucial for refining diagnosis, management, and genetic counseling.
  • Future research needs deep phenotyping, systems biology, and longitudinal studies to understand gene-environment interactions.
Abstract

Keywords:
cardiomyopathyepigeneticsexpressivitygenetic variabilitygenotype–phenotype correlationpenetranceprecision medicine

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