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Atrial Fibrillation — MRCP Part 1 MCQ

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HardCardiologyAtrial FibrillationMRCP Part 1

A 22-year-old man has recurrent low-trauma fractures, short stature, persistently open cranial sutures, hypoplastic clavicles and resorption of the distal phalanges. Bone density is diffusely increased. Which cellular defect best explains this phenotype?

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Correct answer: B — Impaired osteoclast collagen degradation because of cathepsin K deficiency

The best answer is “Impaired osteoclast collagen degradation because of cathepsin K deficiency”. Pycnodysostosis results from biallelic CTSK variants. Cathepsin K is an osteoclast protease needed to degrade type I collagen in the resorption compartment, so affected patients have osteosclerosis yet brittle bone, acro-osteolysis, open sutures and clavicular hypoplasia. TCIRG1 deficiency causes severe infantile osteopetrosis without this characteristic acral and cranial pattern. LRP5 deficiency lowers bone mass; TGFB1 activation causes Camurati-Engelmann disease; and procollagen-processing defects produce osteogenesis-imperfecta phenotypes.

Reference: Pycnodysostosis — GeneReviews: https://www.ncbi.nlm.nih.gov/books/NBK563694/