Emery-Dreifuss Muscular Dystrophy Workup

Updated: May 23, 2019
  • Author: Eli S Neiman, DO, FACN; Chief Editor: Amy Kao, MD  more...
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Workup

Laboratory Studies

The creatinine kinase (CK) level is mildly elevated to less than 10-times normal levels in most cases of Emery-Dreifuss muscular dystrophy (EDMD). If the CK level is extremely elevated, other disorders should be considered, including Duchenne/Becker or limb-girdle muscular dystrophy.

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Other Tests

Needle electromyography (EMG) and nerve conduction studies (NCSs)

EMG and NCSs should be obtained to confirm the myopathic nature of the disease and to exclude other neuromuscular syndromes.

In EDMD, EMG shows small amplitude narrow duration motor unit potentials (MUPs) with early recruitment (as is typical for myopathies).

Fibrillations and positive sharp waves are rare. NCSs are normal.

Electrocardiogram (ECG)

ECG should be obtained in all patients with EDMD.

Early changes include low amplitude P waves and a prolonged PR interval.

Progression to bradycardia, absent P waves, irregular atrial rhythm, atrial fibrillation and flutter, AV-conduction defects, and a late cardiomyopathy all have been reported.

A classic pattern is of a junctional escape rhythm at 40-50 beats per minute without P waves.

Confirmation of the diagnosis is obtained by demonstration of a lack of all electrical and mechanical activity of the atria and an inability to pace the atria confirming that the myocardium, not the conduction system, is affected.

Genetic testing

If emerin is absent or reduced on tissue sample or with a typical presentation and clear X-linked inheritance, EMD should be tested.

With a typical clinical presentation and autosomal dominant inheritance, LMNA should be tested.

Affected females should also undergo genetic testing.

A multi-gene panel that includes EMD, LMNA, and FHL1 (and others) could also be considered.

Whole exome sequencing should be used if the above fails to show abnormality.

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Procedures

A muscle biopsy should be obtained in all patients with presumed EDMD for routine histologic staining. For immunohistochemical studies, antibodies to emerin can help confirm the diagnosis.

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Histologic Findings

Routine histochemical stains show typical myopathic features, including variability in muscle fiber size with small round fibers and occasional necrotic and regenerating fibers. A mild increase in endomysial connective tissue and internal nuclei are often present. Myosin adenosine triphosphatase (ATPase) stains may show type I fiber smallness or type I fiber predominance.

In X-linked EDMD, immunohistochemical staining using an antiemerin antibody shows the absence of normal staining of the inner nuclear membrane in 95% of patients (see image below). A similar pattern is obtained upon staining of peripheral leukocytes, skin fibroblasts, and buccal cells. Furthermore, detection of female carriers is possible because emerin immunostaining is lost from a percentage of muscle fibers.

Left: The photomicrograph is a muscle biopsy with Left: The photomicrograph is a muscle biopsy with normal emerin immunostaining. Right: The micrograph is from a patient with X-linked Emery-Dreifuss muscular dystrophy. Note the absence of nuclear staining as well as the hypertrophied and atrophied muscle fibers.

Immunostaining for lamin A/C is normal in patients with EMD2 as well as in patients with EMD1; therefore, immunostaining results can not be used to diagnose EMD2.

Electron microscopy of patients with EMD1 and EMD2 can show irregularly thickened nuclear lamina, rearranged heterochromatin, chromatin condensation and decondensation, focal chromatin loss or extrusion into the sarcoplasm, nuclear disintegration/fragmentation and tubulofilamentous inclusions within the nuclear matrix. [10]

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Imaging Studies

In a  study utilizing MRI imaging, researchers found that all patients with Emery-Dreifuss muscular dystrophy type 2 showed a characteristic involvement of the posterior calf muscles. They observed that while the medial head of the gastrocnemius was always predominantly involved, the lateral head was relatively spared. This pattern was more obvious in mildly affected patients in whom the other calf muscles were spared or only mildly involved. However, it was also recognizable in the patients with more advanced disease. In contrast, none of the patients with the X-linked EDMD or with Emery-Dreifuss-like phenotype but no mutation in either genes showed this pattern of muscle involvement. Findings suggest that patients with EDMD2 have a specific pattern of muscle involvement and therefore muscle MRI, in combination with other techniques, can be used to distinguish various genetic forms of the disease. [11]

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