Titin-related limb-girdle muscular dystrophy R10

Titin-related limb-girdle muscular dystrophy R10 (LGMDR10), formerly known as LGMD2J, is a rare autosomal recessive muscular dystrophy caused by mutations in the TTN gene, which encodes titin — the largest known human protein and a critical structural component of the sarcomere in skeletal and cardiac muscle. This condition primarily affects the proximal muscles of the limbs, particularly the pelvic and shoulder girdle musculature, leading to progressive muscle weakness and wasting. The disease was originally described in the Finnish population, where a founder mutation (FINmaj) is prevalent. Clinical features typically include progressive proximal lower limb weakness that may begin in childhood, adolescence, or early adulthood, with difficulty walking, climbing stairs, and rising from a seated position. Over time, upper limb girdle muscles may also become affected. Distal muscle involvement, particularly of the anterior tibial compartment, can also occur. Serum creatine kinase (CK) levels are usually elevated. Disease severity can vary, and some patients may eventually require wheelchair assistance. Cardiac involvement, including dilated cardiomyopathy, has been reported in some cases and should be monitored. There is currently no cure or disease-specific treatment for LGMDR10. Management is supportive and multidisciplinary, including physical therapy to maintain mobility and prevent contractures, orthopedic interventions as needed, respiratory monitoring, and cardiac surveillance. Genetic counseling is recommended for affected families. Research into gene therapy and other molecular approaches for titinopathies is ongoing but remains in early stages.

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