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Inherited and progressive myopathy affecting boys. Presents with muscular, respiratory, and cardiac disease.

DMD; Pseudohypertrophic Muscular Dystrophy; Duchenne Type of Progressive Muscular Dystrophy; Progressive Muscular Dystrophy Type I.

Approximately 1:3500 boys is affected, which makes it the most common form of muscular dystrophy. No preferences in race or nationality have been reported. The disease affects almost exclusively males, although females rarely can be affected, for example, when they have a translocation between autosomal chromosomes and the X chromosome, uniparental disomy (i.e., when the chromosome pair or specific segments of a chromosome pair are inherited from one parent only), or suffer from Turner syndrome.

About one third results from spontaneous mutation (negative family history does not exclude DMD); the rest is inherited in an X-gonosomal recessive way. Simplified, in DMD a frameshift mutation results in the absence of dystrophin, whereas in Becker muscular dystrophy a non-frameshift mutation results in decreased levels of dystrophin. The responsible gene (with 2400 kbp, one of the largest known human genes) has been mapped to the short arm of the X chromosome at position 21 (Xp21).

The DMD gene product, a protein called dystrophin, is absent or nonfunctional in patients with DMD. Dystrophin, an important structural part of a large sarcolemmal glycoprotein complex, stabilizes the sarcolemma and plays an important role in the interaction between sarcoplasm and extracellular matrix. Dystrophin is expressed in skeletal and cardiac muscle and in the brain. In the absence of dystrophin (or its function), the entire function of this sarcolemmal complex appears to be disrupted (dystrophin links the actin filaments to the glycoprotein complex in the sarcolemma). This defect may result in either decreased sarcolemmal stability to the mechanical stress of contraction-relaxation or disturbed calcium homeostasis with excessive calcium influx into the muscle cell and pathologic activation of intracellular enzymes. Finally, this results in destruction and necrosis of muscle fibers, which are eliminated by macrophages (myophagocytosis) and later replaced by scar and fat tissue with endomysial and perimysial fibrosis. Although some muscle fibers may show a compensatory hypertrophy, most often the fibers are atrophic, split, or even missing in later stages of the disease. The clinically diagnosed pseudohypertrophy of muscles (particularly the calves) refers to this phenomenon and is, in fact, the result of scarring and fatty degeneration of the muscles, which is muscle wasting.

The clinical course, elevated plasma levels of creatine phosphokinase and other enzymes (e.g., troponin I, lactate dehydrogenase, and transaminases), and muscle biopsy (fatty degeneration and scarring and immunostaining confirm the lack of dystrophin) lead to the diagnosis. Molecular biology allows for intrauterine diagnosis. Age at diagnosis is before birth (familial context), otherwise between 2 and 5 years (occasionally later). Female carriers of the disease may have increased creatine phosphokinase levels, but most often they are clinically asymptomatic.

Progressive and symmetrical wasting of muscles of the legs and pelvis and later of the thorax and upper ...

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