Histology · Year 1 · from Histology
Case 1: Duchenne Muscular Dystrophy
Clinical Image
Source: Wikipedia - Duchenne Muscular Dystrophy - CC BY-SA 3.0
Case Presentation
A 5-year-old boy is brought to the pediatrician because his parents notice he has difficulty climbing stairs and rising from the floor. He uses a characteristic "Gower maneuver" - placing his hands on his thighs and "walking up" his legs to stand from a sitting position. Physical examination reveals enlarged, firm calves (pseudohypertrophy) despite overall muscle weakness, particularly in the proximal muscles. He has a waddling gait and lumbar lordosis. Laboratory studies show markedly elevated serum creatine kinase (CK) at 15,000 U/L (normal <200), indicating ongoing muscle damage. Genetic testing reveals a frameshift deletion in the dystrophin gene on the X chromosome. Muscle biopsy shows variation in fiber size, degenerating and regenerating fibers, increased endomysial connective tissue, and immunohistochemistry confirms absent dystrophin staining. The diagnosis is Duchenne muscular dystrophy (DMD). The family is counseled that this is a progressive condition with wheelchair dependence typically by age 12 and cardiorespiratory complications.
Key Learning Points
- Dystrophin is a critical protein linking the intracellular cytoskeleton (actin) to the extracellular matrix via the dystrophin-associated glycoprotein complex
- Without dystrophin, the sarcolemma is damaged during contraction, leading to muscle fiber necrosis
- Pseudohypertrophy occurs because destroyed muscle is replaced by fat and fibrous tissue, enlarging the calf but weakening it
- The elevated CK reflects ongoing muscle cell membrane damage and release of intracellular contents
- Understanding the normal organization of skeletal muscle (sarcolemma, endomysium, dystrophin) explains the pathophysiology