What is the role of muscle biopsy in the workup of congenital muscular dystrophy (CMD)?

Updated: Jul 03, 2019
  • Author: Emad R Noor, MBChB; Chief Editor: Amy Kao, MD  more...
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Muscle biopsy is indicated in all cases of suspected congenital muscular dystrophy to help confirm the diagnosis and exclude other causes of weakness. 

In congenital muscular dystrophy, the muscle biopsy shows dystrophic changes with abnormal variation in fiber size (associated with whorled or split fibers) and rare hypercontracted fibers. An increase in internal nuclei is evident, with a variable increase in endomysial connective and adipose tissue. Prominent muscle necrosisis infrequent and may be absent in congenital muscular dystrophy.

The immunohistochemical examination is extremely important in the differential diagnosis; specific antibodies for merosin, collagen VI, and glycosylated α-dystroglycan may identify specific protein deficiencies. Depending on the clinical findings, a muscle biopsy may be done early or late in the diagnostic process.

Neurogenic changes may be prominent in MDC1A (merosin deficiency) while immunohistology shows complete or partial deficiency of laminin α2. In complete merosin deficiency, both the C-terminal and N-terminal antibodies to laminin α2 fail to stain muscle fibers. On the other hand, the light chains of laminin α2 (β1 and γ1) are preserved, and other laminin α chains (α4 and α5) are upregulated. Muscle biopsy in MDC1A may be neurogenic but is usually dystrophic. In collagen VI–deficient congenital muscular dystrophies, collagen IV shows normal expression, while collagen VI may or may not label normally. The muscle biopsy commonly shows a range from moderate myopathic changes to severe dystrophic features depending on the severity and duration of the disease. Collagen VI immunostaining is helpful if it shows anabsence or reduction in basement membrane (basal lamina) labeling, but normal labeling does not exclude Ullrich congenital muscular dystrophy or Bethlem myopathy. Immunohistochemistry in α-dystroglycanopathy congenital muscular dystrophy shows normal expression of β-dystroglycan in the sarcolemma, accompanied by absent or reduced α-dystroglycan.

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