Dystrophinopathies

Dystrophinopathies are a group of genetic disorders mainly affecting skeletal and cardiac muscle, caused by deficiency of the protein dystrophin at the sarcolemma of muscle fibers. Dystrophin is encoded by the Duchenne muscular dystrophy gene (DMD), linked to the Xp21 locus. Duchenne muscular dystrophy (DMD) is the severe form of dystrophinopathy caused by a complete deficiency of dystrophin protein, affecting 1 in ~ 4,000 newborn males and representing one of the most common lethal childhood disorders. Becker muscular dystrophy (BMD) is the relatively milder condition caused by the presence of a reduced and/or partially functional dystrophin protein, and its clinical manifestations range from severe to mild. Disease manifestations are relatively rare in DMD/BMD carriers. Dilated cardiomyopathy (DCM) and respiratory insufficiency are the most frequent complications of dystrophinopathies. Mental retardation is found in a small percentage of patients. To date, dystrophinopathies have no definitive cure, but benefit from palliative pharmacological therapy with steroids, and multidisciplinary care for prevention and management of complications. Experimental molecular and genetic therapies are under development but their efficacy has yet to be proven.