Diagnostic Approach to Suspected Muscular Dystrophy

Initial Screening and Genetic Testing

The American College of Medical Genetics recommends beginning with serum creatine kinase (CK) measurement as the initial screening test, which can be performed in primary care settings 1
In suspected Duchenne muscular dystrophy (DMD), CK levels are typically very high, often exceeding 10,000 U/L, according to the American Academy of Neurology 2
If CK is elevated, proceed directly to genetic testing for dystrophin gene deletions or duplications on a blood sample, as suggested by the American College of Medical Genetics 1, 2
Standard genetic tests detect approximately 95% of DMD mutations, according to the National Institute of Neurological Disorders and Stroke 2

Muscle biopsy becomes necessary when genetic testing is negative, to evaluate dystrophin protein expression, as recommended by the American Academy of Neurology 2
The European Neurological Society suggests that muscle biopsy is required in cases of atypical presentations, where clinical features don't fit classic muscular dystrophy patterns 3
The American College of Rheumatology recommends muscle biopsy to confirm inflammatory myopathy and for subclassification, when symptoms suggest inflammatory rather than dystrophic disease 4
The American Academy of Neurology states that muscle biopsy is essential for diagnostic uncertainty, when differentiation between myopathy and neuropathy is needed 3

The absence of dystrophin protein on muscle biopsy is sufficient to confirm dystrophinopathy and guide management as DMD, regardless of genetic test results, according to the American Academy of Neurology 2
The National Institute of Neurological Disorders and Stroke notes that 5% of mutations may be missed by standard genetic testing, highlighting the importance of muscle biopsy in these cases 2

Early diagnosis through genetic testing allows timely initiation of glucocorticoid therapy, which can slow disease progression and improve outcomes, as recommended by the American Academy of Neurology 2

The American College of Medical Genetics recommends that all female family members at risk should receive genetic counseling, and carrier testing should be offered to mothers and sisters 2
The National Society of Genetic Counselors states that genetic counseling is essential regardless of whether diagnosis was made by genetic testing or muscle biopsy 2

The American College of Medical Genetics suggests that if standard deletion/duplication analysis is negative, perform dystrophin gene sequencing to detect point mutations or small deletions/insertions 2
The European Society of Human Genetics recommends advanced molecular analysis including multiplex ligation-dependent probe amplification (MLPA) 2