Muscular Dystrophy

Muscular Dystrophies

The muscular dystrophies—myopathies characterized by progressive degeneration of muscle— are mostly hereditary.

Dystrophinopathies are X-linked recessive disorders due to mutations of the gene encoding dystrophin, a protein found in the cell membrane (sarcolemma) of muscle fibers. Such mutations cause a deficiency, alteration, or absence of dystrophin. The functional features of dystro-phin are not fully understood; it is thought to have a membrane-stabilizing effect. Some forms of limb girdle dystrophy (e.g., sarcogly-canopathy) are due to mutation of genes encoding dystrophin-associated glycoproteins, while others are due to mutation ofgenes encoding in-tracellular enzymes such as calpain-3. Emery-Dreifuss muscular dystrophy is due to a mutation of the gene for emerin, a nuclear membrane protein whose exact function is unknown.

■ Symptoms and Signs

Muscular dystrophies may be characterized by atrophy, hypertrophy, or pseudohypertrophy and are further classified by their mode of inheritance, age of onset, and distribution. Other features such as myocardial involvement, contractures, skeletal deformity, endocrine dysfunction, and ocular manifestations may point to one or another specific type of muscular dystrophy. Each type has a characteristic course (Table 68, p. 400).

The history and physical examination are supplemented by additional diagnostic studies including ECG, creatine kinase fractionation (CK-MM), EMG, and DNA studies. If DNA analysis fails to reveal a mutation, immunohisto-chemical techniques, immune blotting, or the polymerase chain reaction can be used to detect abnormalities of dystrophin and sarcoglycan (e.g., in muscle biopsy samples) and thereby distinguish between Duchenne and Becker muscular dystrophy, or between dystro-phinopathies and other forms of muscular dystrophy. DNA tests are used for the identification of asymptomatic female carriers (in whom muscle biopsy is hardly ever necessary), and for prenatal diagnosis.

The goal of treatment is to prevent contracture and skeletal deformity and to keep the patient able to sit and walk for as long as possible. The patient's diet should be monitored to prevent obesity. The most important general measures are genetic counseling, social services, psychiatric counseling, and educating the patient on the special risks associated with general anesthesia. The type of schooling and employment must be appropriately suited to the patient's individual abilities and prognosis. Physical therapy includes measures to prevent contractures, as well as breathing exercises (deep breathing, positional drainage, measures to counteract increased inspiratory resistance). Patients with alveolar hypoventilation may need intermittent ventilation with continuous positive airway pressure (CPAP) at night. Orthoses may be helpful, depending on the extent of weakness (night splints to prevent talipes equinus, seat cushions, peroneal springs, orthopedic corsets, leg or-thoses). Home aids may be needed as weakness progresses (padding, eating aids, toilet/bathing aids, stair-lift, mechanized wheelchair, specially adapted automobile). Surgery may be needed to correct scoliosis, prevent contracture about the hip joint (iliotibial tract release), and correct winging of the scapula (scapulopexy/scapulode-sis) and other deformities and contractures. In-tracardiac conduction abnormalities (e. g., in Emery-Dreifuss muscular dystrophy) require timely pacemaker implantation. Heart transplantation may be needed when severe cardio-myopathy arises in conjunction with certain types of muscular dystrophy (Becker, Emery-Dreifuss; Table 68, p. 400).

, , , , Dystroqlycan Extracellular matrix, Sarcotubular system œmplex basal lamina

Mitochondria

Sarcolemma

, , , , Dystroqlycan Extracellular matrix, Sarcotubular system œmplex basal lamina

Mitochondria

Sarcolemma

Basal Lamina Myopathy

Emerin Pathogenesis

Merosin Laminin-2 Syntrophins

Sarcolemma Dystrobrevin Calpain-3 Sarcoplasm Nuclear envelope

Proximal muscle weakness

Hyper-lordosis

Emerin Pathogenesis

Proximal muscle weakness and atrophy

Proximal muscle weakness

Calf hypertrophy

Duchenne-type MD

Weakness of lid closure (no ptosis)

Myopathic ies with weakness (shoulder girdle, dorsiflexion) and winged scapula

Proximal muscle weakness

— Calf hypertrophy

Becker dystrophy

Proximal muscle weakness and atrophy

Becker dystrophy

Muscular Dystrophy Calf Muscle

Achilles tendon Emery-Dreifuss dystrophy

MD: Muscular dystrophy

Achilles tendon Emery-Dreifuss dystrophy

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