Emery-Dreifuss Muscular Dystrophy (EDMD)

Relatively benign congenital muscular dystrophy usually beginning in childhood or adolescence and characterized by early muscle contractures (mainly shoulders and upper arms) and cardiac conduction disorders.

Scapuloilioperoneal Atrophy with Cardiomyopathy.

No precise data are available. The X-linked form (males only) is more frequent and has been reported in more than 70 families. The estimated prevalence is approximately 1:100,000 in the general population. The autosomal dominant form is much less frequent.

Two forms of EDMD exist: (1) X-linked, resulting from a mutation in the emerin gene (>100 mutations have been reported and mapped to X28q) that usually results in complete absence of emerin from the muscles, and (2) autosomal dominant, resulting from a mutation in the lamin A/C gene on 1q21. Lamins A/C are part of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane, where they interact with chromatin and other proteins of the inner nuclear membrane (lamina-associated proteins and emerin) through various binding sites. Significant intrafamilial and interfamilial variability have been described. Sporadic cases have been described.

Almost all known mutations result in a complete absence of emerin, an inner nuclear membrane protein not limited to muscle cells but mostly expressed in skeletal and cardiac muscles. It is believed to interact with the nuclear lamins (components of the nuclear lamina), chromatin, and nuclear actin. Its exact role is unknown, but it seems to protect the nuclear membrane from mechanical lesions during muscle contraction. It also may favor reassembly of the nuclear membrane at the end of mitosis. Lamins A/C is also an inner nuclear membrane protein with properties similar to emerin, which would account for the similarity in phenotype between X-linked and autosomal dominant EDMD. For emerin (and presumably lamins A/C) to function properly, the protein must be correctly positioned on the nuclear membrane. Any defect in the nuclear membrane could interfere with skeletal muscle regeneration because emerin seems to play an important role in the organization of the nuclear membrane during cell division. Emerin seems to be associated with cardiac desmosomes and fasciae adherentes, which not only suggests a physiologic role for the protein in cardiac function but also explains the cardiac involvement.

Mainly based on the clinical findings. It is easier to diagnose if a relative has the disease. Serum creatinine kinase levels are moderately increased. Electromyography and nerve conduction studies confirm the myopathic nature of the disease. Muscle biopsy using antibodies to emerin can help confirm the diagnosis in the X-linked form.

The two forms of the disorder are clinically similar. Onset of the clinical manifestations usually occurs in the second or third decade of life. The following triad characterizes the disorder. (1) Early contractures affecting the Achilles tendons (resulting in toe walking), elbows (biceps and triceps), and posterior cervical muscles (initially resulting in limited cervical flexion, which later extends to the whole spine) often occur before any muscle weakness is apparent. (2) Early in the course of the disease, a slowly progressive muscle wasting and weakness (which is rarely severe) with a distinctive humeroperoneal distribution (i.e., proximal in the upper limbs and distal in the lower limbs) can be detected. As the disease progresses, weakness extends to the proximal limb girdle musculature. (3) Cardiac conduction defects may range from sinus bradycardia to prolongation of the PR interval and complete heart block. Atrial paralysis is almost considered pathognomonic of EDMD. A dilated right atrium on echocardiography and isolated atrial standstill and absent P waves on the electrocardiogram should prompt exclusion of EDMD. A generalized cardiomyopathy has been described, resulting in progressive cardiac failure or sudden cardiac death from heart block (which occurs in up to 40% of affected patients). Cardiac involvement is by far the most serious and important feature of this disorder, occurring almost exclusively after muscle weakness has become obvious. Almost all patients show some degree of cardiac involvement by age 30 years. Early diagnosis is crucial, allowing pacemaker implantation before fatal arrhythmias occur. Some patients develop a scoliosis. These patients are mentally normal.

Obtain an electrocardiogram (consider 24-hour Holter ECG), an echocardiogram to assess cardiac function, and a cardiac consultation if the patient has a pacemaker. In the presence of significantly decreased muscle weakness and/or scoliosis, pulmonary function tests should be obtained prior to any major surgery. Prolonged postoperative mechanical ventilation may be required. Check neck mobility, particularly neck extension.

Be prepared for difficult airway management because of patient's neck stiffness. Maintain spontaneous ventilation until the airway has been secured. In the presence of scoliosis, there may be a restrictive pulmonary disease or even cardiac involvement. The presence of contractures makes patient positioning more difficult. Good padding is required. Regional anesthesia per se is not contraindicated; however, proper positioning for central neuraxial blockade may be difficult. The requirement for muscle relaxants will be minimal in patients with muscle weakness. Finally, cardiac involvement is frequent with conduction anomalies, so a defibrillator, resuscitation drugs, and a magnet if the patient has a pacemaker should be available immediately. No association with malignant hyperthermia has been reported.

Succinylcholine should not be used in these patients because of an increased risk of exaggerated hyperkalemia. In the presence of significant cardiomyopathy, myocardial depressant drugs should be avoided. Avoid neuromuscular blockers in suspected difficult airway management until the airway has been secured.

Scapuloperoneal Muscular Dystrophy and Scapuloperoneal Neuropathy have a distribution of weakness similar to that of EDMD but are not genetically defined.