Congenital Muscular Dystrophy Workup

Updated: Jul 03, 2019
  • Author: Emad R Noor, MBChB; Chief Editor: Amy Kao, MD  more...
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Approach Considerations

The most important diagnostic tools are CK level, nerve conduction study, and EMG with or without repetitive nerve stimulation, brain MRI, muscle biopsy, and specific genetic or metabolic testing.




Laboratory Studies

Persons with Ullrich congenital muscular dystrophy, rigid spine with muscular dystrophy (deficiency of selenoprotein N), and integrin-α7 deficiency have creatine kinase (CK) levels that are normal to mildly elevated (≤5 times normal).

CK levels are usually more than 1000 in patients with congenital muscular dystrophy with familial junctional epidermolysis bullosa.

CK levels are mildly to markedly elevated (2-150 times normal) in most patients with congenital muscular dystrophy due to abnormal glycosylation or with laminin-α2 mutations.


Imaging Studies

Persons with congenital muscular dystrophies due to mutations in genes for selenoprotein N and in genes for the extracellular matrix proteins integrin-α7 and collagen type VI have normal brain MRI findings.

Patients CMD with familial junctional epidermolysis bullosa often have brain atrophy and enlarged ventricles on MRI.

In those with congenital muscular dystrophies due to mutations in laminin-α2 or with any other congenital muscular dystrophy due to abnormal O-glycosylation, brain MRI findings are abnormal.

  • The mildest changes are seen in deficiency of laminin-α2, with periventricular white matter changes being the most common abnormality (increased T2 signal).

  • In the congenital muscular dystrophies due to abnormalities in O-glycosylation, the abnormalities vary, even in patients with mutations in the same gene. Brain MRIs can be normal, or they can show severe changes, such as agyria and severe pontocerebellar hypoplasia.

  • All patients with muscle-eye-brain disease and Fukuyama congenital muscular dystrophy have abnormal MRIs, which show a range from mild changes of only cerebellar hypoplasia or cysts to severe disease, as described above.

  • The most severe changes are seen in Walker-Warburg syndrome, with most patients having severe agyria, pontocerebellar hypoplasia, and, in many patients, encephalocele or myelomeningocele.

Muscle MRI can help differentiate muscular dystrophies with rigidity of the spine [56]

  • SEPN1 – Selective involvement of the sartorius, gastrocnemius spared

  • COL6A – Bethlem myopathy (BM) patients had concentric atrophy and peripheral involvement, most obvious in vasti and gastrocnemius

  • COL6A - Ullrich CMD patients had diffuse involvement of thigh muscles with selective sparing of anteromedial thigh muscles; more diffuse than BM, but similar peripheral involvement of gastrocnemius

  • LMNA – Involvement of vasti at thigh level, medial > lateral gastrocnemius, soleus involved

  • LGMD2A (CAPN3) – Selective involvement of adductor magnus and posterior thigh muscles, medial > lateral gastrocnemius, soleus involved


Other Tests

Electromyography (EMG) and nerve conduction study (NCS)

EMG and NCS should be performed in all patients with suspected congenital muscular dystrophy to confirm myopathy and to exclude other diseases.

NCS results are normal except in some cases with mutations in laminin-α2, in which mild neuropathic changes may be seen (some with demyelinating features).

EMG usually shows typical small-amplitude, narrow-duration motor-unit potentials with early recruitment.

Prenatal diagnosis

Prenatal diagnosis had been performed most commonly in families with mutations in laminin-α2, in part, because this is the most common congenital muscular dystrophy.

Laminin-α2 is expressed in 9-week trophoblasts, allowing immunohistochemical detection of protein in chorionic villus. However, in families with partial laminin-α2 deficiency, protein detection may not be reliable. Linkage analysis can also be performed but is also at times unreliable, especially in families with partial laminin-α2 deficiency or no brain MRI abnormalities. However, the combination of these 2 techniques along with rigorous controls has been highly accurate and reliable in the prenatal diagnosis of laminin-α2 mutations. The most reliable technique is direct mutation analysis, although this is more time consuming because the entire gene sequence must be analyzed.

Genetic testing

Genetic testing is available for all congenital muscular dystrophies (see



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.

Congenital muscular dystrophy with laminin-α2 deficiency

  • Complete laminin-α2 deficiency

    • Patients may have severe dystrophic pathology with muscle-fiber degeneration and regeneration, fiber necrosis, and endomysial and perimysial fibrosis.

    • Mononuclear cell infiltrates may be present in biopsy samples obtained from infants.

    • Immunohistochemical studies show complete loss of staining for laminin-α2.

    • Antibodies must be used against both the 300- and 80-kd subunits.

    • α-dystroglycan staining is also absent.

    • Approximately 95% of biopsy samples with absent laminin-α2 staining have a mutation in the LAMA2 gene.

  • Partial laminin-α2 deficiency

    • Mild myopathic features often occur with little or no necrosis.

    • Partial staining for laminin-α2 may be seen in patients with laminin-α2-deficient congenital muscular dystrophy and in those with any congenital muscular dystrophy associated with a glycosyltransferase enzyme deficiency.

Ullrich congenital muscular dystrophy

  • Variation ranges from mildly myopathic to dystrophic in terms of muscle fiber size, muscle fiber necrosis, and fibrosis.

  • Collagen type VI staining around surface of muscle fiber is usually reduced or absent, but staining may occur in connective tissue.

  • In Bethlem myopathy, routine muscle biopsy and collagen type VI immunohistochemistry usually are normal.

Integrin-α7 deficiency

  • Mild variations in muscle-fiber size are noted.

  • Staining for integrin-α7 is decreased. This may also be seen in congenital muscular dystrophy with laminin-α2 deficiency.

Congenital muscular dystrophy with familial junctional epdermolysis bullosa

  • Variation in muscle fiber size, internal nuclei, increased connective tissue, muscle fiber necrosis and regeneration

  • Plectin immunostaining is reduced in muscle Z-lines and skin

Rigid spine with muscular dystrophy (deficiency of selenoprotein N)

  • Myopathic features include small, round muscle fibers, endomysial fibrosis and type 1 fiber predominance or atrophy.

  • Regenerating and degenerating muscle fibers and fiber necrosis are rare. Severe cases may have significant fibrosis but still little or no necrosis.

  • Minicores may be present.

Glycotransferases (abnormal O-glycosylation of α-dystroglycan)

  • All of the α-dystroglycanopathies have similar muscle pathologies that differ in the degree of severity, which is likely correlated with the degree of preserved α-dystroglycan function.

  • Patients have muscle fiber degeneration and/or necrosis and regeneration, variability in muscle fiber size, and endomysial and/or perimysial fibrosis

  • Muscle tissue may look fairly normal in persons with muscle-eye-brain disease and with mutations in FKRP shortly after birth.

  • Immunohistochemical studies show decreased staining for α-dystroglycan, which is localized correctly to the muscle cell surface. Western blot studies show a decreased molecular weight of α-dystroglycan in affected patients. A secondary decrease in staining for laminin-α2 may be noted in some biopsy samples.