Muscular Dystrophy

– A group of inherited, progressive, degenerative muscle disorders characterized by an insidious loss of muscle strength in a variety of muscle groups. Duchenne’s muscular dystrophy (DMD) is the most common of the disorders.

Causes and Incidence

DMD and Becker’s muscular dystrophy (BMD; a clinical variant of DMD) are X-linked recessive disorders involving the gene that encodes dystrophin. Males are exclusively affected, and the incidence in the United States is 1 in every 3,000 live male births. These disorders typically manifest in boys 3 to 7 years of age. Females are carriers. Other dystrophies (Landouzy-Dejerine dystrophy [LDMD], Leyden-Mobius dystrophy [LMMD], Erb’s dystrophy, and mitochondrial and congenital myopathies) are also inherited, but the specific genetic link is less clear. These disorders are seen in children and adults, affect males and females, and are milder.

Disease Process

Dystrophin, a protein product in skeletal muscle, is absent in individuals with DMD and reduced in those with BMD. The resulting pathogenesis is not clear, but lack of dystrophin is thought to impair fast muscle fiber function and to induce a number of biochemical anomalies, including intracellular accumulation of calcium. A number of systemic sequelae have also been noted. Serotonin in the platelets is reduced, and nonmuscle cells have reduced adhesiveness and generalized membrane abnormalities. Central nervous system neuropathology is noted, as is reduced gastrointestinal motility. Platelet function and the vascularity of endothelial cells are abnormal.

Symptoms

DMD
Delays in gross motor development; difficulty walking, running, climbing stairs, and riding a tricycle appears about 3 to 5 years of age; progressive weakness with waddling gait, lordosis, difficulty rising from a sitting or supine position; calf muscle hypertrophy; scoliosis; contractures and joint deformities; inability to ambulate by about age 12; mild mental retardation; respiratory and accessory muscles involved in end stage with cardiomegaly

BMD
Onset occurs at 5 to 25 years of age; symptoms are similar to but milder than DMD; ambulation is lost about 20 years after onset; contractures, scoliosis, and ventilatory failure are rare, and the life span usually is normal

LDMD
Onset from 7 to 20 years of age; weakness of facial and shoulder girdle muscles; difficulty whistling, closing eyes, and raising arms; footdrop develops late; life span is normal

LMMD/Erb’s
Adult onset with weakness of pelvic girdle (LMMD) and shoulder girdle (Erb’s)

Potential Complications

The major complications of DMD are disuse atrophy, contractures, and cardiopulmonary problems, resulting in respiratory infections. Death is usually a result of complications rather than the primary disease.

Diagnostic Tests

DMD and BMD are diagnosed through clinical evaluation and the characteristic manifestations; electromyography reveals rapidly recruited myopathic motor units without spontaneous activity; muscle biopsy shows necrosis and varied muscle fiber size; dystrophin immunoblotting is done in which dystrophin is absent (DMD) or abnormal (BMD). Other types are distinguished primarily on clinical grounds.

Treatments

Surgery
Contracture release; spinal instrumentation to correct scoliosis; tracheostomy in end-stage DMD.

Drugs
Random clinical trials are being conducted with steroids; antiinfective drugs for bacterial infections in end-stage DMD.

General
Long-term rehabilitation (occupational and physical therapy) to maintain activities of daily living and help adapt to progressive loss of function, prevent disuse syndrome, and promote bowel and bladder control; assistive devices (canes, walkers, bracing, casting, wheelchairs); counseling and psychologic support of individual and family; respite home care; ventilatory assistance and communication devices in end-stage DMD; family genetic counseling, identification of carriers.