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🧬 Duchenne Muscular Dystrophy (DMD) — Pediatrics Exam Notes

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1. QUICK FACTS (Memory Pegs)

Mnemonic: "Dystrophin Deficiency = Duchenne" — All three Ds!

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2. PATHOPHYSIOLOGY CHART

MUTATION in DMD gene (Xp21)
          ↓
   Frameshift mutation
          ↓
  ABSENT Dystrophin protein
          ↓
┌──────────────────────────────────────────────────────┐
│  Normally: Dystrophin anchors ACTIN (inside cell)    │
│            to DYSTROGLYCAN COMPLEX (cell membrane)   │
│            to MEROSIN/LAMININ-2 (outside cell)       │
│  → This creates a mechanical "shock absorber" link   │
│    between the sarcomere and the sarcolemma          │
└──────────────────────────────────────────────────────┘
          ↓ Without dystrophin:
  Sarcolemma (cell membrane) becomes UNSTABLE
          ↓
  Ca²⁺ leaks INTO the muscle cell
          ↓
  Calcium activates proteases (calpains)
          ↓
  NECROSIS of muscle fibers
          ↓
  Repeated cycles of necrosis → fibrosis
          ↓
  Muscle replaced by FAT + FIBROUS tissue
          ↓
  Progressive MUSCLE WEAKNESS + WASTING
          ↓
  ┌────────────────┬─────────────────┬──────────────┐
  ↓                ↓                 ↓              ↓
Skeletal      Cardiac           Respiratory   CNS
Muscle Weak   Cardiomyopathy    Failure       Cognitive Sx

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3. CLINICAL FEATURES — AGE-WISE TIMELINE

BIRTH → 2 yrs       : Normal early milestones (appears normal)
                       ↓ subtle toe walking may be noted

2–5 yrs              : PRESENTATION
                       • Delayed walking / waddling gait
                       • Frequent falls
                       • Difficulty climbing stairs
                       • PSEUDOHYPERTROPHY of calves
                         (fat + fibrous tissue replaces muscle)
                       • Gowers' sign positive ←★ EXAM FAVOURITE

5–10 yrs             : PROGRESSION
                       • Proximal muscle weakness (hip > shoulder)
                       • Lordosis, waddling gait
                       • Joint contractures begin

By ~12 yrs           : WHEELCHAIR BOUND
                       (loss of ambulation)

By ~20 yrs           : COMPLICATIONS
                       • Kyphoscoliosis
                       • Respiratory failure (main cause of death)
                       • Dilated cardiomyopathy → heart failure
                       • Fatal arrhythmias

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4. KEY SIGNS — MUST KNOW

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5. INVESTIGATIONS CHART

Suspected DMD (young boy, proximal weakness, calf enlargement)
                ↓
SERUM CK (FIRST TEST)
• Elevated 20–100× normal ← KEY EXAM FACT
• May be elevated even before symptoms appear
                ↓
GENETIC TESTING (DNA analysis of DMD gene)
• Detects ~90–95% of cases
• If POSITIVE → Confirmed DMD
                ↓
If genetic testing NEGATIVE
                ↓
MUSCLE BIOPSY
• Histology: necrosis, regeneration, fibrosis
• Immunostaining: ABSENT dystrophin (except in revertant fibers)
                ↓
Additional:
• ECG + ECHO → cardiomyopathy
• Pulmonary function tests → respiratory reserve
• Cognitive/neuropsychological testing

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6. ASSOCIATED FEATURES (Non-muscle)

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7. MANAGEMENT CHART

                    ┌──────────────────────────┐
                    │  MULTIDISCIPLINARY TEAM  │
                    └──────────────────────────┘
                         ↓         ↓       ↓
                    Neurology  Cardiology  Pulm
                    Ortho      Physio      Nutrition

PHARMACOLOGICAL:

1. CORTICOSTEROIDS ← Most important drug in exams
   • Prednisone: 0.75 mg/kg/day
   • Deflazacort: 0.9 mg/kg/day (less weight gain)
   • Benefits: delays loss of ambulation, improves strength,
     slows scoliosis, helps respiratory function

2. CARDIAC MANAGEMENT (once cardiomyopathy develops)
   • ACE inhibitors → slow myocardial fibrosis
   • Beta-blockers → for heart failure

3. EXON SKIPPING THERAPIES (newer, FDA-approved)
   • Eteplirsen — skips exon 51 (IV, 30 mg/kg/week)
   • Golodirsen / Viltolarsen — skip exon 53
   • Casimersen — skips exon 45
   Goal: restore partial dystrophin production

NON-PHARMACOLOGICAL:
   • Physiotherapy → prevent contractures
   • Splints / orthotics → maintain joint angles
   • Wheelchair when ambulation lost
   • Scoliosis monitoring → spinal fusion if needed
   • Non-invasive ventilation (NIV/BiPAP) for respiratory failure
   • Nutritional support

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8. DMD vs BECKER — COMPARISON TABLE

Key concept: Same gene, different mutation type. DMD = frameshift (no protein). Becker = in-frame (partial protein).

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9. EXAM-FAVOURITE HIGH-YIELD POINTS

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10. ONE-LINE PATHOPHYSIOLOGY (For Short Answer)

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