How to diagnose muscle dystrophy?

Diagnosing Muscular Dystrophy: A Systematic Approach

The diagnosis of muscular dystrophy requires a stepwise approach beginning with clinical suspicion, followed by creatine kinase testing, genetic testing, and in some cases muscle biopsy to confirm the diagnosis and determine the specific type of muscular dystrophy. 1

When to Suspect Muscular Dystrophy

Clinical Presentation

• In children without family history: delayed walking (>16-18 months), Gowers' sign (especially in children <5 years old), frequent falls, difficulty running or climbing stairs 1
• In children with positive family history: any suspicion of abnormal muscle function should prompt investigation 1
• Unexplained elevated transaminases (AST, ALT) in a male child should raise suspicion for muscular dystrophy before proceeding to liver biopsy 1
• Waddling gait often accompanies Gowers' sign and increases suspicion for Duchenne muscular dystrophy (DMD) 1
• Toe walking may be present but is not specifically diagnostic 1

Age Considerations

• DMD is typically diagnosed around 5 years of age but may be suspected earlier due to developmental delays 1
• In children <5 years, a normal muscle examination cannot completely exclude DMD 1
• A boy >10 years with normal muscle function is highly unlikely to have DMD 1

Diagnostic Algorithm

Step 1: Initial Screening

• Measure serum creatine kinase (CK) levels - markedly elevated in muscular dystrophies, especially DMD (typically >1000 U/L) 1
• This can be performed within the primary care setting as an initial screening test 1

Step 2: Genetic Testing

• If CK is elevated, proceed to genetic testing for dystrophin gene mutations 1
• Common genetic tests include:
  • Multiplex PCR (least expensive, detects only deletions, doesn't cover whole gene) 1
  • Multiplex ligation-dependent probe amplification (detects deletions and duplications, covers all exons) 1
  • Single-condition amplification/internal hybridization (detects deletions, provides sequence data) 1
• If deletion/duplication testing is negative, proceed to dystrophin gene sequencing to look for point mutations or small deletions/insertions 1
• Full characterization of the mutation is essential to determine the effect on the reading frame of the gene, which predicts disease progression 1

Step 3: Muscle Biopsy (if needed)

• If genetic testing is inconclusive or unavailable, muscle biopsy should be performed 1
• Key tests on muscle biopsy are immunocytochemistry and immunoblotting for dystrophin 1
• Biopsy should be interpreted by an experienced pathologist 1
• Muscle biopsy can provide information on the amount and molecular size of dystrophin 1
• Target a weak muscle for biopsy, often guided by EMG findings 1
• Typical histopathologic features of muscular dystrophy include:
  • Connective tissue proliferation in perimysium and endomysium
  • Variation in muscle fiber size
  • Internal nuclei and fiber splitting
  • Degeneration and regeneration of myofibers 2

Step 4: Electromyography (EMG)

• EMG helps confirm a myopathic process and can guide muscle biopsy 1
• Characteristic findings include:
  • Polyphasic motor unit action potentials of short duration and low amplitude
  • Increased insertional and spontaneous activity with fibrillation potentials
  • Sharp waves or repetitive discharges 1

Differential Diagnosis Considerations

• Distinguish muscular dystrophies from:
  • Inflammatory myopathies (polymyositis, dermatomyositis) 1
  • Metabolic myopathies 1, 3
  • Endocrine disorders (hypothyroidism, hyperparathyroidism) 1, 4
  • Drug-induced myopathies 1, 4
  • Neurologic disorders affecting the motor neuron or peripheral nerves 3, 4

Post-Diagnosis Steps

• For patients diagnosed by muscle biopsy, dystrophin genetic testing is still necessary 1
• For patients diagnosed by genetic testing, muscle biopsy is optional to distinguish DMD from milder phenotypes 1
• Refer to specialized multidisciplinary follow-up 1
• Provide genetic counseling for at-risk female family members 1
• Connect patient and family with support organizations 1

Clinical Assessment and Monitoring

• Regular assessment of disease progression through:
  • Strength testing (manual muscle testing using MRC scale)
  • Range of motion (goniometry)
  • Timed function tests (10m walk, Gowers' maneuver, stair climbing)
  • Activities of daily living assessment
  • Motor function scales 1
• Routine clinic appointments every 6 months 1
• Specialist physical and occupational therapy assessments every 4 months 1

Common Pitfalls to Avoid

• Don't mistake elevated transaminases for primary liver disease in male children 1
• Don't rule out DMD based on normal muscle examination in children <5 years 1
• Don't stop at genetic testing or muscle biopsy alone - both may be needed for complete diagnosis 1
• Don't forget to consider alternative diagnoses if genetic testing and muscle biopsy are negative for muscular dystrophy 1
• Don't overlook the need for multidisciplinary care and genetic counseling after diagnosis 1