Qualitative or quantitative defects of telethonin

Qualitative or quantitative defects of telethonin (also known as TCAP-related disorders) refer to a group of conditions caused by mutations in the TCAP gene, which encodes the protein telethonin (also called titin-cap). Telethonin is a sarcomeric protein located at the Z-disc of striated muscle, where it plays a critical role in myofibril assembly, sarcomere stability, and mechanosensing in cardiac and skeletal muscle. Defects in this protein can lead to both cardiac and skeletal muscle disease, primarily manifesting as limb-girdle muscular dystrophy type R7 (formerly LGMD2G) and hypertrophic or dilated cardiomyopathy. Patients with limb-girdle muscular dystrophy due to TCAP mutations typically present with progressive proximal muscle weakness affecting the hip and shoulder girdle muscles, difficulty walking, and eventual loss of ambulation. Cardiac involvement, including cardiomyopathy and arrhythmias, may also occur and can be a significant source of morbidity. Calf hypertrophy and elevated serum creatine kinase levels are commonly observed. The age of onset is variable but often begins in childhood or adolescence. There is currently no cure for telethonin-related disorders. Management is supportive and multidisciplinary, including physical therapy to maintain mobility, orthopedic interventions, respiratory support if needed, and cardiac monitoring with appropriate pharmacological treatment for cardiomyopathy or arrhythmias. Genetic counseling is recommended for affected families. Research into gene therapy and other molecular approaches is ongoing but remains in early stages.

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