Duchenne Muscular Dystrophy

1 in 5,000 males, X-linked recessive hereditary condition (1/3 sporadic, from spontaneous mutation). The diagnosis is usually obvious by the fourth year of life and the patient is severely disabled by 10 years of age.

• Delayed motor development first noticed from 18 months to 4 years of age
  • 50% not walking before 18 months
  • waddling gait
  • frequent falling
  • trouble with walking or running
  • poor coordination
  • proximal muscle weakness → Gower’s sign
• 4-6 Years old: some normal muscular development masks the disease process
• Increasing weakness: waddling gait, increased lumbar lordosis, increasing equinus foot, reduced knee jerk (proximal → distal, i.e. ankle jerk preserved until late)
  • pseudo-hypertrophic calves
  • poor at sports
  • cannot keep up with peers
• 9-13 Years old: loss of independent mobility
• Spinal deformity:
  • reduced pulmonary function
  • cardiac failure and arrhythmia
  • mortality 15-25 years
• non-progressive intellectual impairment (average IQ ~ 85)

Diagnosis

• Family History + clinical features
• serum creatine kinase (CK): 100-200 x normal
• electromyography: myopathic pattern
• muscle biopsy:
  • variable fibre diameter, necrosis, regeneration and replacement with flat
    • absence of dystrophin on immune staining
• molecular testing

Management

• Passive physiotherapy
• Corticosteroids
• Genetic counselling

Differential Diagnosis, stratified by anatomical site

• anterior horn
  • acute: e.g. poliomyelitis
  • chronic: e.g. spinal muscular atrophy (Werdnig-Hoffmann disease, autosomal recessive)
• peripheral neuropathy
  • acute neuropathies: e.g. Guillain Barre syndrome (GBS)
  • chronic neuropathies: e.g. peroneal muscle atrophy (Charcot-Marie-Tooth disease, autosomal dominant)
• neuromuscular junction disorder
  • acute: e.g. botulism
  • chronic: e.g. Myasthenia Gravis
• muscle
  • acute myopathies: e.g. toxic rhabdomyolysis
  • chronic myopathies:
    • congenital myopathies
    • progressive muscular dystrophies
      • e.g. Becker muscular dystrophy
      • e.g. Facioscapulohumeral Muscular Dystrophy (FSH, FSHD)
    • myotonic disorders
    • inflammatory myopathies
    • metabolic storage diseases / endocrine myopathies