DMD primarily affects males with an estimated incidence of 1/3,300 male births. Females are usually asymptomatic but a small percentage of female carriers manifest milder forms of the disease (symptomatic form of muscular dystrophy of Duchenne and Becker in female carriers).
Onset occurs in early childhood, and affected boys may show a delay in motor milestones or global developmental delay. Children with DMD generally never achieve the ability to run or jump. The condition progresses rapidly and the child develops a waddling gait and a positive Gower's sign. Climbing stairs becomes difficult and the child begins to fall frequently. Loss of independent ambulation occurs between the ages of 6 and 13 years, the average being 9.5 years in non-steroid treated patients. Once ambulation is lost, joint contractures and scoliosis develop rapidly. Cardiomyopathy and respiratory failure are the cause of death in young adulthood. DMD is an X-linked recessive disease in which the muscle damage is caused by the complete absence of the sarcolemmal protein dystrophin as a result of anomalies in the DMD gene (Xp21.2).
Diagnosis is suspected on the basis of the clinical picture, family history and laboratory findings (serum creatine kinase is 100-200 times the normal level). Muscle biopsy shows dystrophic features and there is a complete absence of the dystrophin protein. DNA studies demonstrate a frame-shift deletion, duplication or nonsense mutation in the DMD gene. Differential diagnoses include severe Becker muscular dystrophy and the limb girdle muscular dystrophies (see these terms). Antenatal diagnosis is possible for families in which the diagnosis has been confirmed by molecular testing.
Genetic counseling is very important: the risk of recurrence is 50% for male fetuses. Female siblings have a 50% risk of being carriers.
Multidisciplinary care is essential.
Physiotherapy includes passive stretching and night time ankle-foot orthoses to reduce tendo-Achilles contractures.
Treatment with corticosteroids (prednisolone, prednisone or deflazacort) is the gold standard. Corticosteroids should be introduced when the child's motor skills plateau, usually between 5-7 years of age. Complications of corticosteroid therapy must be managed and include: weight management, H2 antagonists for gastric protection, regular monitoring and treatment of osteoporosis, and ophthalmic assessment for cataracts and glaucoma.
Regular cardiac monitoring is required to allow early treatment with ACE inhibitors.
Surgery may be required for correction of the scoliosis and nocturnal BIPAP is beneficial for the treatment of restrictive respiratory failure.
DMD has a severe prognosis and life expectancy is significantly reduced with death occurring in early adulthood.
Expert reviewer(s)
- Dr Rosaline QUINLIVAN