A 5-year-old boy is unable to walk on heels, falls frequently, and has calf pseudohypertrophy. His CK is 18,000 IU/L. Genetic testing shows a frameshift deletion in the DMD gene preventing production of any dystrophin protein. Which inheritance pattern and mechanism of muscle damage are CORRECT?
- A Autosomal recessive; defective myosin heavy chain leads to contraction failure
- B X-linked dominant; truncated dystrophin disrupts Z-disc alignment
- C X-linked recessive; absence of dystrophin destabilizes the dystrophin-glycoprotein complex, causing membrane fragility and calcium influx ✓
- D Autosomal dominant; haploinsufficiency of dystrophin with secondary mitochondrial dysfunction
Explanation
Duchenne Muscular Dystrophy (DMD) is X-linked recessive, caused by out-of-frame (frameshift) deletions/duplications in the DMD gene that prevent any dystrophin synthesis. Dystrophin normally connects the intracellular actin cytoskeleton to the extracellular matrix via the dystrophin-associated glycoprotein complex (DGC). Without dystrophin, the DGC disassembles, the sarcolemmal membrane becomes fragile, and muscle contraction causes calcium influx → protease activation → fiber necrosis. Becker MD arises from in-frame mutations producing a truncated but partially functional dystrophin. Calf pseudohypertrophy results from replacement of necrotic muscle fibers with fat and connective tissue. CK is massively elevated (10–100× normal) due to membrane leakage.
Reference: Ghai Essential Pediatrics, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.