Qualitative or quantitative defects of beta-myosin heavy chain (MYH7)

Qualitative or quantitative defects of beta-myosin heavy chain (MYH7) refer to a group of conditions caused by mutations in the MYH7 gene, which encodes the beta-myosin heavy chain protein. This protein is a major structural and functional component of the sarcomere — the basic contractile unit of cardiac and slow-twitch skeletal muscle fibers. Defects in MYH7 can be qualitative (producing an abnormal protein) or quantitative (producing insufficient amounts of normal protein), both of which disrupt normal muscle contraction and function. MYH7 mutations are associated with a spectrum of cardiac and skeletal muscle diseases. The most well-known associated condition is hypertrophic cardiomyopathy (HCM), characterized by abnormal thickening of the heart muscle, which can lead to heart failure, arrhythmias, and sudden cardiac death. MYH7 defects can also cause dilated cardiomyopathy (DCM), left ventricular noncompaction, and restrictive cardiomyopathy. In some patients, skeletal myopathy may also be present, including Laing distal myopathy and myosin storage myopathy, which can cause muscle weakness predominantly in distal or proximal limb muscles. Key symptoms across these conditions include exercise intolerance, dyspnea (shortness of breath), palpitations, chest pain, syncope, and progressive muscle weakness. Treatment is largely supportive and depends on the specific phenotype. For cardiomyopathies, management may include beta-blockers, calcium channel blockers, antiarrhythmic medications, implantable cardioverter-defibrillators (ICDs) for those at risk of sudden cardiac death, and in severe cases, heart transplantation. For skeletal myopathies, physical therapy and rehabilitation are the mainstays of care. Cardiac mavacamten, a selective cardiac myosin inhibitor, has been approved for obstructive HCM and represents a targeted therapeutic advance. Genetic counseling is recommended for affected individuals and their families due to the hereditary nature of these conditions.

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