Atlas of pathophysiology, 2 Edition

Part II - Disorders

Musculoskeletal disorders

Muscular dystrophy

Muscular dystrophy is a group of congenital disorders characterized by progressive symmetric wasting of skeletal muscles without neural or sensory defects. Paradoxically, some wasted muscles tend to enlarge (pseudohypertrophy) because connective tissue and fat replace muscle tissue, giving a false impression of increased muscle mass. The prognosis varies with the form of disease. The four main types of muscular dystrophy include:

·   Duchenne's, or pseudohypertrophic (50% of all cases)—strikes during early childhood, is usually fatal during the second decade of life, and affects 13 to 33 per 100,000 persons, mostly males

·   Becker's, or benign pseudohypertrophic (milder form of Duchenne's)—becomes apparent between ages 5 and 15, is usually fatal by age 50, and affects 1 to 3 per 100,000 persons, mostly males

·   Facioscapulohumeral (Landouzy-Dejerine) and limb-girdle—usually manifests in second to fourth decades of life, doesn't shorten life expectancy and affects both sexes equally.

Clinical Tip

Possible complications of Duchenne's muscular dystrophy are:

·   weakened cardiac and respiratory muscles leading to tachycardia, electrocardiographic abnormalities, and pulmonary complications

·   sudden heart failure, respiratory failure, infection.

Causes

Genetic mechanisms, typically causing an enzymatic or metabolic defect

·   Duchenne's or Becker's muscular dystrophy—X-linked recessive disorders; mapped to the Xp21 locus for the muscle protein dystrophin, which is essential for maintaining muscle cell membrane; muscle cells deteriorate or die without it

·   Limb-girdle muscular dystrophy—autosomal recessive disorder

·   Facioscapulohumeral muscular dystrophy—autosomal dominant disorder.

Pathophysiology

Abnormally permeable cell membranes allow leakage of a variety of muscle enzymes, particularly creatine kinase. The metabolic defect that causes the muscle cells to die is present from fetal life onward. The absence of progressive muscle wasting at birth suggests that other factors compound the effect of dystrophin deficiency. The specific trigger is unknown, but phagocytosis of the muscle cells by inflammatory cells causes scarring and loss of muscle function.

As the disease progresses, skeletal muscle becomes almost totally replaced by fat and connective tissue. The skeleton eventually becomes deformed, causing progressive immobility. Cardiac muscle and smooth muscle of the GI tract typically become fibrotic. The brain exhibits no consistent structural abnormalities.

Signs and symptoms

Duchenne's (pseudohypertrophic)

·   Insidious onset between ages 3 and 5

·   Initial effects on legs, pelvis, shoulders

§  Enlarged, firm calf muscles

§  Waddling gait, toe-walking, and lumbar lordosis

§  Difficulty climbing stairs

§  Frequent falls

§  Positive Gower's sign—patient stands from a sitting position by “walking” hands up legs to compensate for pelvic and trunk weakness

Becker's (benign pseudohypertrophic)

·   Similar to those of Duchenne's type but with slower progression

Facioscapulohumeral (Landouzy-Dejerine)

·   Weak face, shoulder, and upper arm muscles (initial sign)

§  Pendulous lip and absent nasolabial fold

§  Abnormal facial movements; absence of facial movements when laughing or crying

§  Masklike expression

·   Inability to raise arms above head

Limb-girdle

·   Weakness in upper arms and pelvis (initial sign)

·   Lumbar lordosis, protruding abdomen

·   Winging of scapulae

·   Waddling gait, poor balance

·   Inability to raise arms

Diagnostic test results

·   Electromyography shows short, weak bursts of electrical activity in affected muscles.

·   Muscle biopsy shows a combination of muscle cell degeneration and regeneration (in later stages, showing fat and connective tissue deposits).

·   Immunologic and molecular biological techniques facilitate accurate prenatal and postnatal diagnosis of Duchenne's and Becker's muscular dystrophies.

Treatment

Supportive only

·   Coughing and deep-breathing exercises

·   Diaphragmatic breathing

·   Teaching parents to recognize early signs of respiratory complications

·   Orthopedic appliances, physical therapy

·   Surgery to correct contractures

·   Adequate fluid intake, increased dietary bulk, and stool softener

·   Low-calorie, high-protein, high-fiber diet

·   Genetic counseling

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MUSCLES AFFECTED IN DIFFERENT TYPES OF MUSCULAR DYSTROPHY

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