Duchenne and Becker myodystrophy.

Duchenne and Becker muscular dystrophies are X-linked recessive disorders characterized by progressive proximal muscle weakness due to muscle fiber degeneration. Becker muscular dystrophy has a later onset and is less severe.

The diagnosis is suggested clinically and confirmed by measuring the protein (dystrophin) produced by the mutated gene. Treatment focuses on maintaining function with physical therapy and the use of braces and orthotics; prednisolone is given to some patients with severe loss of function.

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What causes Duchenne and Becker muscular dystrophy?

Duchenne and Becker muscular dystrophies are caused by mutations in the Xp21 locus. In Duchenne muscular dystrophy, the mutation results in the absence of dystrophin, a cell wall membrane protein. In Becker muscular dystrophy, the mutation results in abnormal or insufficient amounts of dystrophin. Duchenne muscular dystrophy occurs in 1/3,000 live-born boys; Becker muscular dystrophy occurs in 1/30,000 live-born boys.

Symptoms of Duchenne and Becker muscular dystrophy

Duchenne muscular dystrophy usually appears between the ages of two and three years. Proximal muscle weakness develops, usually beginning in the lower extremities. Children develop a waddling gait, a toe-walking gait, and lordosis. These children often fall, and have difficulty running, jumping, climbing stairs, and getting off the floor. Duchenne muscular dystrophy progresses steadily, causing flexion contractures of the joints and scoliosis. Dense pseudohypertrophy (fatty and fibrous replacement of individual enlarged muscle groups, especially the calf muscles) develops. Most patients are confined to a wheelchair by age 12 and die of respiratory complications by age 20. Heart disease is usually asymptomatic, although 90% of patients have abnormal ECGs. One third of patients experience mild, non-progressive intellectual disability, with impairments on verbal rather than non-verbal tests.

Becker muscular dystrophy becomes clinically apparent much later, and its symptoms are less pronounced. Patients are usually able to walk until at least age 15, and many remain ambulatory into adulthood. Most affected patients live more than 30-40 years.

Diagnosis of Duchenne and Becker muscular dystrophy

The diagnosis is suspected based on characteristic clinical manifestations, age of onset, and family history indicating an X-linked inheritance pattern. Signs of myopathy are detected by electromyography (rapidly evoked, short, low-amplitude motor potentials) and muscle biopsy (necrosis and marked differences in muscle fiber size). Creatine kinase levels may increase up to 100 times normal.

The diagnosis is confirmed by immunostaining of dystrophin. Dystrophin is not detected in patients with Duchenne dystrophy; in patients with Becker dystrophy, dystrophin is usually abnormal (lower molecular weight) or present in reduced concentrations. DNA analysis of peripheral blood leukocytes for mutations can also confirm the diagnosis if abnormalities of the dystrophin gene are detected (deletions and duplications in about 65% and point mutations in about 25% of patients).

Carrier detection and prenatal diagnosis are possible using conventional methods (pedigree analysis, creatine kinase determination, fetal sex determination) in combination with DNA analysis and immune staining of muscle tissue with antibodies to dystrophin.

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Treatment of Duchenne and Becker muscular dystrophy

There is no specific treatment for Duchenne and Becker muscular dystrophy. Moderate exercise is encouraged as long as possible. Passive exercise may prolong the period during which the patient can walk and does not require a wheelchair. Leg bracing with knee and foot traction helps prevent flexion during sleep. Leg braces may temporarily help the patient maintain walking or standing function. Obesity should be avoided; caloric requirements in these patients are lower than normal for their age. Referral of the patient and family for genetic counseling is also indicated.

Daily prednisolone does not result in long-term clinical improvement, but it probably slows the progression of the disease. There is no consensus on the long-term effectiveness of prednisolone. Gene therapy is currently unavailable. Sometimes Duchenne and Becker muscular dystrophy require corrective surgery. In the presence of respiratory failure, noninvasive respiratory support (eg, nasal mask) may be used. Elective tracheostomy is gaining acceptance, allowing the patient to live more than 20 years.