Emery-Dreifuss Muscular Dystrophy (EMD)

Emery-Dreifuss muscular dystrophy (EMD) refers to a group of muscular dystrophies with weakness, contractures, and cardiac conduction abnormalities. Inheritance pattern is variable among subtypes.

EMERY-DREIFUSS 1 (EMD1). EMD1 is an X-linked recessive progressive dystrophic myopathy due to an abnormality of the protein "emerin" with a gene locus identified at Xq28 (99,100). The protein is associated with the subcellular nucleus and cytoplasm membranes and is found in muscle, nerve, mucosal epithelium, skin, and cardiac tissue. Patients usually present in teenage years but the age of presentation may vary from the neonatal period with hypotonia to the third decade. Early elbow flexion contractures are a hallmark of the disease. Severe contractures including elbow flexion, ankle equinus, rigid spine, and neck extension contractures are often more limiting than weakness which begins in a scapulohumeral peroneal distribution. The biceps and triceps show wasting and weakness and the deltoids and forearms are often more spared. The calf frequently shows wasting. Ankle dorsiflexors often are weaker than ankle plantar flexors leading to the equinus contractures. Scapular winging is frequent. Tightness of the cervical and lumbar spinal extensor muscles, resulting in limitation of neck and trunk flexion, with inability to flex the chin to the sternum and to touch the toes, also has been reported in EMD. The face is either spared or affected late. Functional difficulties are experienced walking or climbing stairs. Progression is slow and loss of ambulation is rare. Some cases with EMD1 may show evidence of nocturnal hypoventilation, as a result of restrictive expansion of the chest in association with the rigid spine, and partly due to involvement of the diaphragm.

Progressive cardiac disease is almost invariably present with onset in the early second decade to the forties. Arrhythmia may lead to emboli or sudden death in early adult life. The cardiomyopathy may progress to LV myocardial dysfunction or four-chamber dilated cardiomyopathy due to fibrosis with complete heart block and ventricular arrhythmias (101). Initially, atrial arrhythmia usually appears prior to complete heart block. Reported features include first-degree heart block, followed by the Wenckebach phenomenon and then complete atrial ventricular dissociation and atrial fibrillation or flutter with progressive slowing of the heart rate (101). Frank syncope may develop in the late second and early third decade and patients often require a cardiac pacemaker by age 30 with an indication being bradycardia with a heart rate below 50. EKG changes include slow heart rate, absent or small P-waves, arteriovenous (AV) block, and atrial fibrillation/flutter. Evidence of cardiac arrhythmia, sometimes only present at night, may be detected on 24-hour Holter monitoring. A significant percentage of female carriers have conduction defects and arrhythmias, so they warrant monitoring with annual EKGs.

Laboratory evaluation is usually with molecular genetic studies and/or muscle biopsy. Serum CK is mildly elevated to less than 10 times the normal value and levels decrease with age. MRI of posterior calf shows the soleus to be involved and the gastrocnemius to be relatively spared. Muscle biopsy shows variable muscle fiber size, endomysial fibrosis, inflammation, Type I fiber atrophy, Type I or II predominance, and nuclear membrane pathology on electron microscopy. Other muscle changes in some patients include rimmed vacuoles as seen in inclusion body myositis ("IBM-like")- Immunohistochemistry reveals Emerin loss in muscle in greater than 95% of patients.

EMERY-DREIFUSS MUSCULAR DYSTROPHY 2. EMD2 is due to a lamin A/C protein abnormality and it has been linked to chromosome lq21.2. Inheritance may be dominant or recessive and lamin A/C mutations may be either frameshift or missense (99). Those with missense mutations have childhood onset with a mean age of onset of 2.4 years. Weakness is in a scapuloperoneal and facial distribution. Patients demonstrate paravertebral weakness or rigidity, and tendon contractures are common. Those with frameshift mutations producing a truncated protein have adult onset with a mean age of 30.5 years, and cardiomyopathy is more frequent than weakness (99). Contractures are rare and weakness is in a limb girdle distribution. The disorder is allelic with autosomal-dominant LGMD IB.

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