• A 2-year-old boy presents with fatigue and difficulty with walking. The mother describes her child as “clumsy,” as he usually falls while walking. The mother also reports difficultly with climbing the stairs, which is new. The mother recalls that a relative died in his teens and also experienced muscle weakness when he was very young. On physical exam, there is weakness in the proximal muscles of the lower extremity, bilateral enlargement of the calves, and a positive Gower sign. (Duchenne muscular dystrophy)
  • Clinical definition
    • inherited disorder of skeletal muscle leading to progressive muscle weakness
  • Epidemiology
    • incidence
      • Duchenne muscular dystrophy
        • most common early onset form
      • Becker muscular dystrophy
        • a relatively common form that typically presents later in life
    • demographics
      • male children
        • recall that males have only one X-chromosome
  • Etiology
    • X-linked recessive mutation in the dystrophin gene 
      • Duchenne muscular dystrophy
        • frameshift or deletion of the dystrophin gene
          • results in complete loss of dystrophin
      • Becker muscular dystrophy
        • non-frameshift 
          • results in partial function of dystrophin
          • in other words, the reading frame is not disrupted
  • Pathogenesis
    • normal biology
      • dystrophin is one of the largest human genes and appears to be involved in
        • preventing muscle fiber degeneration by providing mechanical stability between the myofiber and its cell membrane
          • connecting actin to α- and β-dystroglycan transmembrane proteins
        • cell signaling
      • dystrophin is expressed in cardiac, skeletal, and neural tissue
    • pathology
      • absent or decreased function of dystrophin leads to cycles of muscle fiber degeneration and regeneration
        • this subsequently leads to fatty replacement and a distorted fascicular architecture
  • Prognosis
    • Duchenne muscular dystrophy
      • mean age of death is 25 to 30 years of age secondary to
        • heart failure
        • respiratory failure
    • Becker muscular dystrophy
      • less severe than Duchenne muscular dystrophy
  • Symptoms
    • progressive muscle weakness
      • most severe in the proximal muscles and lower extremity
    • waddling gait
  • Physical exam
    • Gower sign
      • a patient using their upper extremity to stand
        • signifies weakness of the proximal lower extremity muscles
    • calf pseudohypertrophy
    • lumbar lordosis
    • hypo- or areflexia
  • Creatine kinase
    • elevated
  • Muscle biopsy
    • degeneration and regeneration
    • muscle replacement by fat and connective tissue
  • Genetic analysis 
    • gold standard
  • Immunostaining
    • absent dystrophin
  • Limb-girdle muscular dystrophy
  • Spinal muscular atrophy
  • Becker muscular dystrophy
  • Approach to management
    • treatment for both Duchenne and Becker muscular dystrophy is multidisciplinary to manage symptoms and complications
      • e.g., physical therapy to maintain ambulation and prevent contractures
  • Medical
    • glucocorticosteroids
      • indication
        • mainstay of treatment for patients with Duchenne muscular dystrophy
      • drugs
        • prednisone
        • deflazacort
      • adverse effects
        • weight gain
        • hirsutism
        • cushingoid appearance
  • Muscular
    • wheel chair bound
  • Cardiac
    • dilated cardiomyopathy
    • arrhythmia
  • Orthopedic
    • fractures secondary to falling

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