Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is typically defined by the presence of left ventricular hypertrophy (LVH) that is not solely explained by abnormal loading conditions. HCM is a significant cause of sudden cardiac death in competitive athletes. The clinical features of HCM are highly variable ranging from asymptomatic LVH to arrhythmias, to refractory heart failure. The symptoms include shortness of breath, orthostasis, presyncope, syncope, palpitations, and chest pain.

The prevalence in the general population is estimated at 1/500.

HCM is most commonly caused by mutations in one of the genes that encode different components of the sarcomere and is inherited in an autosomal dominant manner. In 3–5% of the cases affected individuals carry two mutations in the same gene (compound heterozygous or homozygous), or in different genes (digenic). This is associated with a more severe phenotype with younger age of onset and more adverse events.

 

> Ordering information for NGS panel

 

Indications for genetic testing:

  1. Confirmation of clinical diagnosis
  2. Determination of differential diagnosis
  3. Testing of at-risk family members
  4. Genetic counseling

 

References:

Cirino AL and Ho C. Hypertrophic Cardiomyopathy Overview. GeneReviews®. 2008 August 5 (Updated 2014 Jan 16) 
Elliott PM et al. 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy. European Heart Journal (2014) 35, 2733–2779.
Maron BJ. Sudden death in young athletes. N Engl J Med. 2003;349:1064–75.
Richard P et al. Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy. Circulation 2003; 107: 2227–2232.
Richard P et al. Homozygotes for a R869G mutation in the beta-myosin heavy chain gene have a severe form of familial hypertrophic cardiomyopathy. J Mol Cell Cardiol 2000; 32: 1575–1583.