Muscular Dystrophies, Duchenne & Becker

Key Features

Essentials of Diagnosis

• Progressive degeneration of skeletal and cardiac muscle occurs

General Considerations

• Duchenne muscular dystrophy (DMD)

  • Results from failure of synthesis of the muscle cytoskeletal protein dystrophin

  • The DMD gene is located on the X chromosome, at position Xp21.1-p21.2

  • Approximately 1 in 4000 male children is affected

• Becker muscular dystrophy (BMD)

  • A less severe phenotype than DMD

  • Results from mutations in the same gene that result in partial expression of the dystrophin protein

• Evolution of the natural history of dystrophinopathies in females is demonstrating an increased incidence of serious cardiovascular disease, including cardiomyopathy and arrhythmias

• Large deletions or duplications can be detected in the gene for dystrophin in 65% of cases

Clinical Findings

• In both DMD and BMD, progressive degeneration of skeletal and cardiac muscle occurs

• Boys with DMD exhibit proximal muscle weakness and pseudohypertrophy of calf muscles by age 5–6 years

• Patients become nonambulatory by age 13 years

Diagnosis

• Serum creatine kinase levels are markedly elevated

• Molecular analysis has largely replaced muscle biopsy for diagnostic purposes

Treatment

• Corticosteroids (prednisone/prednisolone or deflazacort)

  • Extend independent ambulation by approximately 2.5 years

  • Preserve respiratory strength and cardiac function into the second decade

  • Instituting steroid treatment between 4 and 8 years, when motor function plateaus or is in decline, appears to have the greatest impact on muscle strength and cardiorespiratory function

Outcome

Prognosis

• Boys with DMD frequently die in their twenties of respiratory failure and cardiac dysfunction

• Prognosis for BMD is more variable

Reference