eMedicine Specialties > Neurology > Pediatric Neurology

Emery-Dreifuss Muscular Dystrophy: Differential Diagnoses & Workup

Author: Glenn Lopate, MD, Associate Professor, Department of Neurology, Division of Neuromuscular Diseases, Washington University School of Medicine; Chief of Neurology, St Louis ConnectCare, Consulting Staff, Barnes Jewish Hospital
Contributor Information and Disclosures

Updated: Jan 8, 2009

Differential Diagnoses

Congenital Muscular Dystrophy
Myasthenia Gravis
Congenital Myopathies
Spinal Muscular Atrophy
Dermatomyositis/Polymyositis
Facioscapulohumeral Dystrophy
Limb-Girdle Muscular Dystrophy

Other Problems to Be Considered

Becker dystrophy
Bethlem myopathy
Duchenne dystrophy
Rigid spine syndrome
Scapuloperoneal muscular dystrophy
Scapuloperoneal neuronopathy

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.

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.

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.

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 (see Media file 1). 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.

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.4

More on Emery-Dreifuss Muscular Dystrophy

Overview: Emery-Dreifuss Muscular Dystrophy
Differential Diagnoses & Workup: Emery-Dreifuss Muscular Dystrophy
Treatment & Medication: Emery-Dreifuss Muscular Dystrophy
Follow-up: Emery-Dreifuss Muscular Dystrophy
Multimedia: Emery-Dreifuss Muscular Dystrophy
References
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References

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  8. Bonne G, Di Barletta MR, Varnous S, et al. Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss muscular dystrophy. Nat Genet. Mar 1999;21(3):285-8. [Medline].

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  12. Chakrabarti A, Pearce JM. Scapuloperoneal syndrome with cardiomyopathy: report of a family with autosomal dominant inheritance and unusual features. J Neurol Neurosurg Psychiatry. Dec 1981;44(12):1146-52. [Medline].

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  31. van Berlo JH, de Voogt WG, van der Kooi AJ, et al. Meta-analysis of clinical characteristics of 299 carriers of LMNA gene mutations: do lamin A/C mutations portend a high risk of sudden death?. J Mol Med. Jan 2005;83(1):79-83. [Medline].

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Further Reading

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Keywords

EDMD, Duchenne muscular dystrophy, Duchenne and Becker muscular dystrophies, nuclear envelope protein, emerin, EMD1, EMD2, lamin, lamin A/C, nesprins, F-actin, EMD gene, LMNA gene, cardiomyopathy, sudden cardiac death, hereditary myopathy, cardiac disease, bradycardia, rhythm disturbances, atrial cardiac conduction defects, syncope, contractures, pulmonary failure, heart failure

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Contributor Information and Disclosures

Author

Glenn Lopate, MD, Associate Professor, Department of Neurology, Division of Neuromuscular Diseases, Washington University School of Medicine; Chief of Neurology, St Louis ConnectCare, Consulting Staff, Barnes Jewish Hospital
Glenn Lopate, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Medical Editor

James J Riviello Jr, MD, George Peterkin Endowed Chair in Pediatrics, Professor of Pediatrics, Section of Neurology and Developmental Neuroscience, Professor of Neurology, Peter Kellaway Section of Neurophysiology, Baylor College of Medicine; Chief of Neurophysiology, Director of the Epilepsy and Neurophysiology Program, Texas Children's Hospital
James J Riviello Jr, MD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Kenneth J Mack, MD, PhD, Senior Associate Consultant, Department of Child and Adolescent Neurology, Mayo Clinic
Kenneth J Mack, MD, PhD is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, Phi Beta Kappa, and Society for Neuroscience
Disclosure: Nothing to disclose.

CME Editor

Matthew J Baker, MD, Consulting Staff, Collier Neurologic Specialists, Naples Community Hospital
Matthew J Baker, MD is a member of the following medical societies: American Academy of Neurology
Disclosure: Nothing to disclose.

Chief Editor

Amy Kao, MD, Assistant Professor, Department of Pediatrics, Division of Pediatric Neurology, Department of Neurology, Oregon Health and Science University; Consulting Staff, Shriners Hospital for Children
Amy Kao, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, and Child Neurology Society
Disclosure: Nothing to disclose.

 
 
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