What is the workup for a patient suspected of having muscular dystrophy?

Diagnostic Workup for Muscular Dystrophy

The diagnostic workup for muscular dystrophy should begin with serum creatine kinase (CK) measurement as the initial screening test, followed by genetic testing for specific mutations, with muscle biopsy reserved for cases where genetic testing is inconclusive. 1, 2

When to Suspect Muscular Dystrophy

Clinical Presentations Without Family History

• Delayed walking (>16-18 months) 3, 2
• Gowers' sign (using hands to "climb up" the legs when rising from floor), especially in children <5 years old 3
• Frequent falls or difficulty with running and climbing stairs 3, 2
• Waddling gait 3
• Toe walking (though less specific) 3

Other Scenarios Warranting Investigation

• Any suspicion of abnormal muscle function in a child with positive family history of muscular dystrophy 3, 2
• Unexplained elevated liver enzymes (AST, ALT) in a male child 3, 2
• Elevated transaminases with normal γ-glutamyl transferase 4
• Developmental delays, particularly in speech or language 3, 4

Diagnostic Algorithm

Step 1: Initial Screening

• Measure serum creatine kinase (CK) levels - markedly elevated levels (>1000 U/L) strongly suggest muscular dystrophy 3, 4
• Physical examination focusing on muscle strength, Gowers' sign, and gait pattern 3, 2

Step 2: Genetic Testing (if CK is elevated)

• Begin with dystrophin deletion/duplication testing 3, 1

  • Multiplex PCR (detects deletions but doesn't cover whole gene) 3, 5
  • Multiplex ligation-dependent probe amplification (MLPA) (detects deletions and duplications across all exons) 3, 5
  • Single-condition amplification/internal hybridization (detects deletions and provides sequence data) 3, 2

• If deletion/duplication testing is negative, proceed to:

  • Full dystrophin gene sequencing to identify point mutations or small deletions/insertions 3, 5

Step 3: Muscle Biopsy (if genetic testing is inconclusive)

• Key tests include:
  • Immunocytochemistry for dystrophin 3, 6
  • Immunoblotting for dystrophin 3
  • Histological assessment for connective tissue proliferation, fiber size variation, and degeneration/regeneration patterns 6

Post-Diagnostic Steps

• For patients diagnosed by muscle biopsy, dystrophin genetic testing is still necessary 3, 5
• For patients diagnosed by genetic testing, muscle biopsy is optional to distinguish between DMD and milder phenotypes 3
• Refer to specialized multidisciplinary follow-up 3, 1
• Provide genetic counseling for at-risk female family members 3, 1
• Connect patients and families with support organizations 1, 2

Important Considerations

• False-negative results are possible in screening programs - clinical suspicion should guide further testing despite negative initial results 7
• Comprehensive testing should include all exons of the gene, as single-exon deletions and duplications account for approximately 22% of cases 5
• A normal muscle examination in a child under 5 years cannot completely exclude muscular dystrophy 3
• A boy older than 10 years with normal muscle function is highly unlikely to have DMD 3
• Screening will identify other muscle disorders beyond DMD, including Becker muscular dystrophy and forms of limb-girdle and congenital muscular dystrophies 6, 7

Pitfalls to Avoid

• Don't proceed to liver biopsy in a male child with elevated transaminases without first checking CK levels 3, 4
• Don't rely solely on multiplex PCR for genetic testing, as it may not fully characterize deletions 3, 5
• Don't stop at deletion/duplication testing if negative in suspected DMD cases - proceed to full gene sequencing 3, 5
• Don't overlook the possibility of muscular dystrophy in children with speech delay or autism spectrum features 1, 4
• Don't neglect to test both sexes, as females can be manifesting carriers 4, 7