The MYH7 gene provides instructions for creating a protein known as the beta-myosin heavy chain. This protein is a component of both cardiac (heart) muscle and specific skeletal muscles, which are responsible for body movement. Mutations within this gene can disrupt its normal function, potentially leading to various health issues affecting both the heart and skeletal muscles.
Normal Function of the MYH7 Gene
The MYH7 gene is responsible for producing the beta-myosin heavy chain, a protein found in heart muscle and type I skeletal muscle fibers. Type I fibers, also known as slow-twitch fibers, are resistant to fatigue and are common in muscles used for posture, such as those in the neck. This protein is part of a larger structure called type II myosin, which consists of two heavy chains from the MYH7 gene and two pairs of light chains from other genes.
Each heavy chain has a head region, or motor domain, that interacts with actin, a protein involved in cell movement, and a tail region that interacts with other proteins. Type II myosin generates the mechanical force required for muscle contraction. In the heart, its regular contractions pump blood throughout the body, while in skeletal muscles, coordinated contraction and relaxation allow for movement.
Health Conditions Linked to MYH7 Mutations
Mutations in the MYH7 gene are associated with several hereditary cardiovascular disorders, collectively known as cardiomyopathies, which impair the heart’s ability to pump blood. These mutations can disrupt the normal structure and function of cardiac myosin, leading to abnormal muscle contraction and relaxation.
Hypertrophic Cardiomyopathy (HCM) is a common condition caused by MYH7 gene mutations. This condition involves the thickening of the heart muscle, particularly the left ventricle, without other causes like high blood pressure. This thickening can obstruct blood flow and increase the risk of heart failure and sudden cardiac death. These mutations can lead to the altered protein not functioning properly.
Left Ventricular Noncompaction (LVNC) is another heart condition linked to MYH7 mutations. In LVNC, the lower left chamber of the heart does not develop correctly during fetal development, resulting in a thick, spongy, and uncompacted muscle that cannot contract effectively. This can lead to a weakened heart muscle that struggles to pump blood, potentially causing irregular heart rhythms, shortness of breath, and heart failure.
MYH7 mutations also contribute to skeletal muscle disorders, including Laing distal myopathy and myosin storage myopathy. Laing distal myopathy typically presents with early-onset muscle weakness, affecting various parts of the body. This condition is characterized by progressive muscle weakness, particularly in the arms and legs. Myosin storage myopathy, another myopathy, involves the accumulation of myosin protein clumps, leading to muscle weakness in the scapula, limbs, and distal muscles.
Detecting MYH7 Gene Mutations
Detecting MYH7 gene mutations and related conditions involves clinical evaluations and specialized tests. Genetic testing, such as DNA sequencing, is a primary method used to identify specific mutations in the MYH7 gene. This testing can confirm a diagnosis, help assess prognosis, and guide management strategies. Genetic testing can also identify at-risk individuals even before symptoms appear.
Clinical diagnostic tools assess the impact of MYH7 mutations on the heart. Echocardiograms are commonly used to visualize the heart muscle, revealing thickening of the heart walls. Electrocardiograms (ECGs) assess the heart’s electrical activity, detecting abnormal rhythms. For skeletal muscle myopathies, a muscle biopsy might be performed to examine muscle tissue for structural abnormalities or protein clumps.
Managing MYH7-Related Conditions
Managing health conditions caused by MYH7 mutations involves a personalized approach focused on symptom relief and preventing complications. Medical management includes medications aimed at improving heart function or controlling symptoms.
Lifestyle adjustments are also part of management. Patients might need to modify physical activity levels to reduce strain on the heart or affected muscles. In some cases, surgical interventions may be considered. For hypertrophic cardiomyopathy, a septal myectomy, a procedure to remove a portion of the thickened heart muscle, can be performed to improve blood flow. Additionally, devices like pacemakers or implantable cardioverter-defibrillators (ICDs) can be implanted to regulate heart rhythm and prevent sudden cardiac death.
Inheritance and Genetic Counseling
MYH7 gene mutations are inherited in an autosomal dominant pattern. This means that a person needs to inherit only one copy of the mutated gene from either parent to be affected by the condition. If one parent has an MYH7 mutation, there is a 50% chance that each child will inherit the mutation.
Genetic counseling plays a role for individuals and families affected by or at risk for MYH7-related conditions. Genetic counselors can explain the inheritance patterns, help families understand their risks, and discuss options for family screening and reproductive planning. Early family screening is recommended once a family member is diagnosed, allowing for timely detection and intervention for those who have inherited the mutation.