A physician-validated, board-style question from the Active Transport QBank. Try it, then check the reasoning for every option.
A 3-year-old is brought to the pediatrician by by his mother. She is concerned that he appears fatigued all the time. She also mentions that he struggles to get out of his seat after eating his meals and when he waddles when he walks now. The child was born at 39 weeks via spontaneous vaginal delivery. He is up to date on all his vaccines and meeting all developmental goals. A maternal uncle with similar symptoms that started in early childhood. He has a heart rate of 90/min, respiratory rate of 22/min, blood pressure of 110/65 mm Hg, and temperature of 37.0°C (98.6°F). The child appears lethargic. He was much more active during his previous well-child visit. Upon examination, the child has thick calves and uses his hands to support himself as he stands up from a sitting position. His reflexes are decreased bilaterally. Lab studies show elevated creatinine phosphokinase (CPK) and lactate dehydrogenase (LDH). Which of the following is the most likely cause of this patient’s condition?
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A
Missense mutation in β-thalassemia geneIncorrect. Beta-thalassemia is a hemoglobinopathy causing microcytic anemia, not muscular dystrophy, and is unrelated to the DMD gene.
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B
Missense mutation in DMD geneIncorrect. Missense mutations in DMD produce a partially functional dystrophin and cause the milder Becker muscular dystrophy (later onset, ambulatory into adulthood), not Duchenne.
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C
Nonsense mutation in DMD geneCorrect. Nonsense mutations introduce a premature stop codon, abolishing dystrophin production and causing the severe Duchenne phenotype seen in this 3-year-old.
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D
Mutation in WT geneIncorrect. The WT (Wilms tumor) gene is involved in renal embryonal tumors and genitourinary development, not skeletal muscle disease.
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E
Trinucleotide repeat expansion in DMPK geneIncorrect. DMPK trinucleotide repeat expansion causes myotonic dystrophy, which presents in adolescence/adulthood with myotonia, frontal balding, and cataracts — not early-childhood proximal weakness with calf pseudohypertrophy.
↑ Tap an answer to reveal the reasoning
Answer: C. A young boy with proximal muscle weakness (difficulty rising from a chair), calf pseudohypertrophy ("thick calves"), Gowers sign (using hands to climb up his own body), waddling gait, decreased reflexes, markedly elevated CPK, and X-linked family history (affected maternal uncle) has Duchenne muscular dystrophy. DMD is caused by mutations in the DMD gene on Xp21 encoding dystrophin. The most severe phenotype — DMD — results from frameshift or nonsense mutations that abolish dystrophin production. Becker muscular dystrophy, a milder allelic variant, typically results from in-frame deletions or missense mutations that produce a partially functional protein.
Nonsense mutations introduce a premature stop codon, truncating the protein and leaving no functional dystrophin. Missense mutations in DMD produce a partial-function protein and cause the milder Becker dystrophy, not Duchenne. Beta-thalassemia and WT (Wilms tumor) gene mutations are unrelated to muscular dystrophy.
Clinical pearl: onset by age 5, wheelchair dependence by adolescence, and death in the 20s–30s from cardiac or respiratory failure. Newer therapies include exon-skipping antisense oligonucleotides and gene therapy.
**Why each option:**
**A.** Beta-thalassemia is a hemoglobinopathy causing microcytic anemia, not muscular dystrophy, and is unrelated to the DMD gene.
**B.** Missense mutations in DMD produce a partially functional dystrophin and cause the milder Becker muscular dystrophy (later onset, ambulatory into adulthood), not Duchenne.
**C.** Correct. Nonsense mutations introduce a premature stop codon, abolishing dystrophin production and causing the severe Duchenne phenotype seen in this 3-year-old.
**D.** The WT (Wilms tumor) gene is involved in renal embryonal tumors and genitourinary development, not skeletal muscle disease.