EMERY-DREIFUSS MUSCULAR DYSTROPHY

 EMERY-DREIFUSS MUSCULAR DYSTROPHY

There are at least five genetically distinct forms of EDMD. Emerin mutations are the most common cause of X-linked EDMD, although mutations in FHL1 may also be associated with a similar phenotype, which is X-linked as well. Mutations involving the gene for Lamin A/C (LMNA) are the most common cause of autosomal dominant EDMD (also known as LGMD1B) and are also a common cause of hereditary cardiomyopathy. Less commonly, autosomal dominant EDMD has been reported with mutations in SYNE2, TMEM43, SUN1, SUN2 and TTN genes encoding nesprin-1, nesprin-2, LUMA, SUN1, SUN2 and titin , respectively.

Clinical Features Prominent contractures can be recognized in early childhood and teenage years, often preceding muscle weakness. The contractures persist through the course of the disease and are present at the elbows, ankles and neck. Muscle weakness affects humeral and peroneal muscles at first and later spreads to a limb distribution. The cardiomyopathy is potentially life threatening and may result in sudden death. A spectrum of atrial rhythm and conduction defects includes atrial fibrillation and paralysis and atrioventricular heart block. Some patients have a dilated cardiomyopathy. Female carriers of the X-linked variant may manifest with a cardiomyopathy.

Laboratory Features Serum CK is usually slightly elevated, and the EMG is myopathic. Muscle biopsy usually shows nonspecific dystrophic features, although cases associated with FHL1 mutations have features of myofibrillar myopathy. Immunohistochemistry reveals absent emerin staining of myonuclei in X-linked EDMD due to emerin mutations. Electrocardiograms (ECGs) demonstrate atrial and atrioventricular rhythm disturbances.

   X-linked EDMD usually arises from defects in the emerin gene encoding a nuclear envelope protein. FHL1 mutations are also a cause of X-linked scapuloperoneal dystrophy but can also present with an X-linked form of EDMD. The autosomal dominant disease can be caused by mutations in the LMNA gene encoding Lamin A/C; in the synaptic nuclear envelope protein 1 (SYNE1) or 2 (SYNE2) encoding nesprin-1 and nesprin-2, respectively; and in TMEM43 encoding LUMA. These proteins are essential components of the filamentous network underlying the inner nuclear membrane. Loss of structural integrity of the nuclear envelope from defects in emerin, Lamin A/C, nesprin-1, nesprin-2 and LUMA accounts for overlapping phenotypes.

TREATMENT

Emery-Dreifuss Muscular Dystrophy

Supportive care should be offered for neuromuscular disability, including ambulatory aids, if necessary. Stretching of contractures is difficult. Management of cardiomyopathy and arrhythmias (e.g., early use of a defibrillator or cardiac pacemaker) may be lifesaving