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Discordant clinical features of identical hypertrophic cardiomyopathy twins

Giuliana G Repetti1, Yuri Kim1,2, Alexandre C Pereira3

  • 1Department of Genetics, Harvard Medical School, Boston, MA 02115.

Proceedings of the National Academy of Sciences of the United States of America
|March 4, 2021
PubMed

Insights

Identical twins with hypertrophic cardiomyopathy (HCM) show different disease progression, indicating that non-genetic factors significantly influence this heart muscle disease. Environmental and epigenetic factors play a crucial role in HCM

Area of Science:

  • Cardiology
  • Genetics
  • Epigenetics

Background:

  • Hypertrophic cardiomyopathy (HCM) is a heart muscle disease affecting approximately 1 in 500 individuals.
  • HCM is characterized by increased left ventricular wall thickness and is often caused by genetic variants in sarcomere protein genes.
  • Clinical expression of HCM varies significantly, even among individuals with the same genetic variant.

Purpose of the Study:

  • To investigate the influence of genetic and environmental factors on the variable clinical expression of hypertrophic cardiomyopathy.
  • To determine the role of nonheritable factors in disease progression among monozygotic twins with HCM.

Main Methods:

  • Studied disease progression in 11 pairs of monozygotic (identical) twins diagnosed with hypertrophic cardiomyopathy.
  • Collected echocardiographic data (left ventricular wall thickness, left atrial diameter, ejection fraction) over 5 to 14 years.
  • Performed whole genome sequencing on twins with discordant phenotypes.

Main Results:

  • All nine twin pairs with known genetic variants and two with unknown etiologies exhibited discordant cardiac morphology.
  • Whole genome sequencing did not identify significant somatic genetic variants explaining the phenotypic discordance.
  • Identical twins displayed differing disease manifestations, underscoring the impact of nonheritable influences.

Conclusions:

  • Nonheritable factors, including epigenetics and environment, significantly influence the clinical expression and progression of hypertrophic cardiomyopathy.
  • Genetic predisposition alone does not fully determine HCM phenotype; environmental and epigenetic interactions are critical.
  • Further research into epigenetic modifications and environmental exposures is warranted for understanding HCM variability.

Keywords:
geneticshypertrophic cardiomyopathyidentical twins

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