What is the genetic cause of hypertrophic obstructive cardiomyopathy?

• A. Mitochondrial inheritance
• B. Autosomal dominant mutation in beta-myosin heavy-chain gene
• C. Truncating mutation in dystrophin
• D. Autosomal recessive mutation in troponin

Answer: (B)

Hypertrophic obstructive cardiomyopathy is driven by inherited defects in the heart’s sarcomeric proteins, most commonly transmitted in an autosomal dominant pattern. The classic gene involved is the beta-myosin heavy chain gene, a key motor protein in the sarcomere. A pathogenic mutation here disrupts sarcomere function, leading to myocyte disarray and disproportionate thickening of the interventricular septum. This septal hypertrophy narrows the left ventricular outflow tract and can create dynamic obstruction, especially during systole, contributing to the obstructive presentation.

There are other sarcomeric gene mutations that can cause HCM, but an autosomal dominant mutation in beta-myosin heavy chain is the prototypical and most common genetic cause. In contrast, mitochondrial inheritance is seen with different cardiomyopathies that involve maternal transmission; truncating mutations in dystrophin are associated with muscular dystrophy and a dilated/pralected cardiomyopathy pattern rather than classic HCM; and while troponin mutations can cause HCM, they do not define the typical genetic scenario as strongly as beta-myosin heavy chain mutations.