MD Musculoskeletal and Connective Tissue 4 — Questions and Answers
Question 1: A 16-year-old boy has tall stature, arachnodactyly, lens dislocation upward, and an aortic root diameter of 4.8 cm. Mutation in which gene is responsible?
- FBN1 (fibrillin-1) (Correct answer)
- COL1A1 (type I collagen)
- ELN (elastin)
- ACTA2 (smooth muscle actin)
Correct answer: FBN1 (fibrillin-1)
Marfan syndrome is caused by mutations in FBN1 encoding fibrillin-1, disrupting microfibrils and TGF-β signaling, affecting connective tissue in multiple organ systems.
Question 2: A 10-year-old girl has hyperextensible skin, hypermobile joints, and easy bruising. Skin biopsy shows abnormal collagen cross-linking. She likely has a defect in which enzyme?
- Lysyl oxidase (Correct answer)
- Prolyl hydroxylase
- Lysyl hydroxylase
- Collagenase
Correct answer: Lysyl oxidase
Ehlers-Danlos syndrome (classical type) involves defective lysyl oxidase or collagen genes, impairing collagen cross-linking and resulting in skin and joint laxity.
Question 3: A 2-year-old child has multiple fractures, blue sclerae, dentinogenesis imperfecta, and hearing loss. What is the underlying molecular defect?
- Mutation in COL1A1 or COL1A2 causing defective type I collagen (Correct answer)
- Deficiency of alkaline phosphatase
- Mutation in FGFR3 causing abnormal bone growth
- Deficiency of vitamin D 1-alpha hydroxylase
Correct answer: Mutation in COL1A1 or COL1A2 causing defective type I collagen
Osteogenesis imperfecta results from mutations in type I collagen genes (COL1A1/COL1A2), producing structurally abnormal collagen that weakens bone, sclerae, and teeth.
Question 4: A 35-year-old woman with diffuse systemic sclerosis develops progressive dyspnea. High-resolution CT shows basal-predominant ground-glass opacities and honeycombing. Which antibody is most associated with this pulmonary complication?
- Anti-Scl-70 (anti-topoisomerase I) (Correct answer)
- Anti-centromere
- Anti-Jo-1
- Anti-U1 RNP
Correct answer: Anti-Scl-70 (anti-topoisomerase I)
Anti-Scl-70 antibodies are associated with diffuse cutaneous systemic sclerosis and a higher risk of interstitial lung disease.
Question 5: A 60-year-old woman develops proximal muscle weakness, elevated CK, and an EMG showing myopathic changes. Muscle biopsy reveals perifascicular atrophy. What is the diagnosis?
- Dermatomyositis (Correct answer)
- Polymyositis
- Inclusion body myositis
- Muscular dystrophy
Correct answer: Dermatomyositis
Perifascicular atrophy is pathognomonic for dermatomyositis, reflecting ischemia from complement-mediated microangiopathy of muscle capillaries.
Question 6: A 40-year-old man with ankylosing spondylitis has failed NSAIDs. Which biologic class is most effective for his axial disease?
- TNF-alpha inhibitors (e.g., adalimumab) (Correct answer)
- IL-6 receptor antagonists (e.g., tocilizumab)
- B-cell depletion agents (e.g., rituximab)
- CTLA-4 Ig fusion proteins (e.g., abatacept)
Correct answer: TNF-alpha inhibitors (e.g., adalimumab)
TNF-alpha inhibitors are first-line biologics for ankylosing spondylitis refractory to NSAIDs; IL-17 inhibitors are an alternative, but IL-6 and rituximab show limited efficacy for axial disease.
Question 7: A 58-year-old woman presents with polyarthralgia, malar rash, photosensitivity, and pleuritis. ANA is 1:640 with a speckled pattern. Which antibody is most specific for her condition?
- Anti-Smith (anti-Sm) (Correct answer)
- Anti-Ro/SSA
- Anti-histone
- Anti-U1 RNP
Correct answer: Anti-Smith (anti-Sm)
Anti-Smith antibodies are highly specific for SLE (though not sensitive), targeting snRNP proteins involved in mRNA splicing.
MD Musculoskeletal and Connective Tissue 4
A 16-year-old boy has tall stature, arachnodactyly, lens dislocation upward, and an aortic root diameter of 4.8 cm.
Mutation in which gene is responsible?