Duchenne’s Muscular Dystrophy

Pathophysiology

1) progressive muscle degeneration occurring in boys, due to absent dystrophin 2) Becker’s muscular dystrophy – less severe clinically; considered a variant of Duchenne’s (dystrophin is present but is smaller than normal)

Signs and Symptoms

1) infants normal at birth, but within 4 years muscle weakness begins (especially in pelvic and shoulder girdles) 2) pseudohypertrophy of calf muscles 3) gait becomes clumsy (or ambulation is never obtained 4) Gowers’ sign 5) contractures in heel cords 6) progressive, painful scoliosis 7) cardiomyopathy 8) respiratory difficulties occur increasingly through teen years 9) patients are usually wheelchair boung by age 12 and usually die by age 21 (often due to pulmonary infection)

Characteristic Test Findings

Laboratory – 1) increased serum CK 2) prenatal and carrier genetic diagnoses are available

Histology/Gross Pathology

1) breakdown of sarcolemma 2) degeneration and necrosis of muscle fibers 3) type 1 and 2 myofibrils attempt to repair and regenerate 4) eventual fibrosis and loss of skeletal muscle fibers 5) diminished/absent dystrophin in muscle fibers 6) replacement of muscle fibers with fibrofatty connective tissue 7) sparing of muscle spindle fibers 8) abnormal presence of dystrophin cerebral cortex muscle

Biochemistry

1) missing dystrophin results in inability of actin to bind to extracellular matrix 2) abnormal calcium influx across defective surface membrane elicits excessive contraction and eventual necrosis

Inheritance/Epidemiology

1) 70% X-linked; 30% sporadic 2) mulitple defects in gene (Xp21) have been described 3) occurs in 1/3500 male births

Treatment

1) palliative treatment with glucocorticoids slows progression for several years 2) gene therapy trials offer possible long-term palliation

Tips for USMLE

1) Gowers’ sign is using hands to push up from floor 2) if the question mentions greatly increased serum CK, think Duchenne’s 3) if the question describes a previously normal 3 year-old boy whose gait has become more clumsy and whose calves seem to be overly muscular, think Duchenne’s