What are the diagnostic steps for muscular dystrophy?

Diagnostic Approach to Muscular Dystrophy

The diagnosis of muscular dystrophy requires a systematic approach combining clinical assessment, laboratory testing, genetic analysis, and in some cases muscle biopsy to confirm the diagnosis and determine the specific type.

Initial Clinical Evaluation

• Key clinical features to recognize:

  • Delayed developmental milestones (not walking by 16-18 months)
  • Gowers' sign (using hands to "climb up" the legs when rising from floor)
  • Waddling gait
  • Proximal muscle weakness
  • Family history of muscular dystrophy

• Physical examination focus:

  • Distribution and symmetry of muscle weakness (typically proximal)
  • Muscle hypertrophy or atrophy
  • Joint contractures
  • Spinal deformities
  • Cardiac abnormalities

Laboratory Testing

1. First-line testing:

   • Serum creatine kinase (CK) - markedly elevated in most muscular dystrophies
   • Liver enzymes (AST, ALT) - often elevated due to muscle breakdown
   • Complete blood count
   • Comprehensive metabolic panel
   • Inflammatory markers (ESR, CRP)
   • Thyroid function tests

2. Electrophysiological studies:

   • Electromyography (EMG) - shows myopathic pattern
   • Nerve conduction studies - typically normal

Genetic Testing

• Genetic testing is essential for definitive diagnosis and should be performed even if muscular dystrophy is confirmed by muscle biopsy 1

• Sequential genetic testing approach:

  1. Multiplex ligation-dependent probe amplification (MLPA) or multiplex PCR to detect deletions/duplications
  2. If negative, proceed to dystrophin gene sequencing to detect point mutations or small deletions/insertions 1
  3. Full characterization of the mutation is required to determine the reading frame effect, which predicts disease progression 1

Muscle Biopsy

• Indications for muscle biopsy:

  • When genetic testing is inconclusive
  • To distinguish between different types of muscular dystrophies
  • To evaluate dystrophin expression

• Key muscle biopsy tests:

  • Immunocytochemistry for dystrophin
  • Immunoblotting for dystrophin
  • Histopathological examination for dystrophic changes 1

Functional Assessments

• Strength testing:

  • Manual muscle testing using MRC scale
  • Quantitative myometry (for muscle strength 3-5 on MRC scale)

• Range of motion:

  • Goniometry to assess joint mobility and contractures

• Functional tests:

  • Timed 10-meter walk
  • Timed Gowers' maneuver
  • Time to climb 4 stairs
  • Time to rise from chair
  • 6-minute walk test 1

• Motor function scales:

  • Vignos lower extremity scale
  • North Star Ambulatory Assessment
  • Brooke upper extremity scale
  • Motor function measure 1

Diagnostic Algorithm

1. Suspect muscular dystrophy if:

   • Male child with delayed motor milestones
   • Gowers' sign present
   • Proximal muscle weakness
   • Waddling gait
   • Positive family history

2. Screen with serum CK - markedly elevated levels suggest muscular dystrophy

3. Genetic testing:

   • Deletion/duplication testing first
   • If negative, proceed to gene sequencing

4. If genetic testing is inconclusive:

   • Perform muscle biopsy for dystrophin analysis

5. After diagnosis:

   • Complete genetic testing (if diagnosis was made by biopsy)
   • Refer to specialized multidisciplinary team
   • Provide genetic counseling for at-risk family members
   • Connect with patient support organizations 1

Important Considerations

• A normal muscle examination in a child under 5 years cannot completely exclude DMD 1
• A boy older than 10 years with normal muscle function is highly unlikely to have DMD 1
• Different genetic testing techniques have varying sensitivity and coverage - multiple methods may be needed 1
• Muscle biopsy should be interpreted by an experienced pathologist 1
• Regular assessments (every 6 months) are essential to monitor disease progression 1

By following this systematic diagnostic approach, clinicians can accurately diagnose muscular dystrophy, determine its specific type, and implement appropriate management strategies to improve patient outcomes and quality of life.