Distal myopathy with anterior tibial onset

Distal myopathy with anterior tibial onset, also known as Udd myopathy or tibial muscular dystrophy (TMD), is a rare inherited muscle disorder characterized by progressive weakness and wasting that initially affects the muscles of the anterior compartment of the lower legs, particularly the tibialis anterior muscle. This condition was first described in Finnish populations and is sometimes referred to as Finnish tibial muscular dystrophy. It is caused by mutations in the TTN gene, which encodes titin, the largest known protein and a critical structural component of the sarcomere in skeletal and cardiac muscle. The disease typically presents in adulthood, usually after age 35, with difficulty in dorsiflexion of the ankles, leading to foot drop and a steppage gait. Weakness is initially confined to the anterior tibial muscles but may slowly progress to involve other distal leg muscles over years to decades. Proximal muscles are generally spared or only mildly affected in the dominant form. The progression is usually slow, and most patients retain the ability to walk, though ankle-foot orthoses may be needed. Serum creatine kinase levels are normal or only mildly elevated. Muscle biopsy typically shows myopathic changes with rimmed vacuoles in affected muscles. There is currently no curative treatment for distal myopathy with anterior tibial onset. Management is supportive and symptomatic, including physical therapy to maintain mobility and strength, ankle-foot orthoses to compensate for foot drop, and regular monitoring for potential cardiac involvement, as some TTN mutations can be associated with cardiomyopathy. Notably, individuals who are homozygous for certain TTN mutations may present with a more severe limb-girdle muscular dystrophy phenotype (LGMD2J), highlighting the importance of genetic counseling for affected families.

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