Hypertrophic cardiomyopathy (HCM) is primarily caused by genetic mutations that affect the proteins responsible for the structure and function of heart muscle cells. These mutations lead to abnormal thickening (hypertrophy) of the heart muscle, especially the walls of the left ventricle, which is the main pumping chamber of the heart.
At the core of HCM’s cause are changes in the genes that encode sarcomere proteins. Sarcomeres are the fundamental units of muscle contraction in heart cells, and they include proteins like beta-myosin heavy chain, myosin-binding protein C, and troponin T. Mutations in these genes disrupt the normal assembly and function of the sarcomere, causing the heart muscle cells to grow abnormally large and disorganized. This disarray leads to thickened heart walls that are less flexible and can obstruct blood flow out of the heart.
Most cases of HCM are inherited in an autosomal dominant pattern, meaning a single copy of the mutated gene from one parent can cause the disease. However, the severity and specific features of the disease can vary widely even within the same family, due to differences in the exact mutation and other genetic or environmental factors.
The thickening of the heart muscle in HCM is not uniform. It often affects the interventricular septum, the wall between the left and right ventricles, more than other areas. This uneven thickening can narrow the left ventricular outflow tract, the path through which blood leaves the heart to the body. During heart contraction, this narrowing can worsen, sometimes pulling the mitral valve leaflets toward the septum and causing obstruction to blood flow. This dynamic obstruction can increase the pressure inside the heart and lead to symptoms like chest pain, shortness of breath, and fainting.
Besides genetic mutations, other factors can influence the development and progression of hypertrophic cardiomyopathy. These include:
– **Modifier genes:** Other genes may affect how severely the heart muscle thickens or how symptoms develop.
– **Environmental influences:** Factors such as high blood pressure or intense physical activity might exacerbate the condition in some individuals.
– **Cellular mechanisms:** The mutated proteins can cause changes in how heart muscle cells grow, how they handle calcium (which is critical for contraction), and how they communicate with each other, contributing to the disease process.
In rare cases, hypertrophic cardiomyopathy can develop without a clear family history, possibly due to new mutations or other unknown causes.
Overall, hypertrophic cardiomyopathy is a complex genetic heart disease caused mainly by mutations in sarcomere protein genes that lead to abnormal thickening and dysfunction of the heart muscle, especially affecting the left ventricle and its outflow tract. This thickening can cause obstruction, impaired relaxation, and electrical instability in the heart, which underlie the clinical features of the disease.
