genetics

Last reviewed 08/2021

Genetic factors play a role in the pathogenesis of idiopathic dilated cardiomyopathy (IDC) (1,2,3,4).

There is a family history in about 20% -50% (1,3) of IDC patients.

There are more than 60 genes which have been identified as being associated with dilated cardiomyopathy (3).

The most frequent mode of inheritance is autosomal dominant.

The disease gene in families with X-linked dilated cardiomyopathy has been identified as dystrophin.

Other genes which may be involved in IDC are found on chromosomes 9 and 1.

In familial arrhythmogenic right ventricular dysplasia, three different disease loci have been identified so far: two on the long arm of chromosome 14 and one on chromosome 1.

The lamin A/C gene (LMNA) and dilated cardiomyopathy:

• approximately 6% of all DCM cases are caused by mutations in the lamin A/C gene (LMNA)
  • LMNA codes for type-V intermediate filaments that support the structure of the nuclear membrane and are involved in chromatin structure and gene expression
  • most LMNA mutations result in striated muscle diseases while the rest affects the adipose tissue, peripheral nervous system, multiple tissues or lead to progeroid syndromes/overlapping syndromes
  • patients with LMNA mutations exhibit a variety of cellular and physiological phenotypes
  • it was reported that seven percent of LMNA mutation carriers exhibit cardiac-related phenotypes if under 20 years of age, 66% when carriers are between 20 and 39, 86% when carriers are between 40 and 59 years, and 100% when carriers are over 60 years of age (4)

Reference:

• Mestroni, L., J. Milasin, et al.. Genetic factors in dilated cardiomyopathy. Archives des Maladies du Coeur et des Vaisseaux 1996;2(15): 15-20.
• Leiden, J. M.. The genetics of dilated cardiomyopathy-emerging clues to the puzzle. New England Journal of Medicine 1997; 337(15): 1080-1.
• Ghosh N, Haddad H: Recent progress in the genetics of cardiomyopathy and its role in the clinical evaluation of patients with cardiomyopathy. Curr Opin Cardiol 2011, 26:155-164.
• Pasotti M et al. Long-term outcome and risk stratification in dilated cardiolaminopathies. J Am Coll Cardiol 2008, 52:1250-1260.