WBR0166

Author	[[PageAuthor::William J Gibson (Reviewed by Yazan Daaboul, M.D. and Alison Leibowitz [1])]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Genetics
Sub Category	SubCategory::Endocrine
Prompt	[[Prompt::A 7-year-old girl is brought to the pediatrician's office for vaginal spotting. Upon further questioning, the mother reports that her daughter's history is significant for a "birthmark" that is pictured from a previous visit (shown below) and several bone fractures throughout childhood. Physical examination is remarkable for breast tissue development, presence of pubic hair, and a palpable lump of the craniofacial bone. Xrays of the patient's proximal femur and the skull base demonstrate expansile lesions with endosteal scalloping and a ground-glass appearance of the intramedullary tissue. Skeletal abnormalities associated with his patient's condition are caused by which of the following mechanism? ]]
Answer A	AnswerA::Increased osteoclastic activity
Answer A Explanation	[[AnswerAExp::Osteoporosis involves an imbalance of skeletal resorption and skeletal formation, leading to poor mineralization and skeletal fragility. Increased osteoclastic activity causes osteoporosis.]]
Answer B	AnswerB::Decreased mineralization of osteoid
Answer B Explanation	[[AnswerBExp::Decreased mineralization of osteoid often results in rickets, which is a softening of the bones in children, potentially leading to fractures and deformity. The predominant cause of rickets is a vitamin D deficiency, but also may result from diets lacking adequate calcium.]]
Answer C	AnswerC::Inappropriately increased PTH secretion
Answer C Explanation	[[AnswerCExp::In primary hyperparathryroidism, the excessive PTH production often results in osteitis fibrosa cystica.]]
Answer D	AnswerD::Increased osteoblastic and osteoclastic activity
Answer D Explanation	[[AnswerDExp::Paget's disease of bone is caused by increased bone turnover.]]
Answer E	AnswerE::Replacement of bone with fibrous tissue
Answer E Explanation	[[AnswerEExp::Polyostotic fibrous dysplasia is a feature of McCune-Albright Syndrome.]]
Right Answer	RightAnswer::E
Explanation	[[Explanation::McCune-Albright syndrome (MAS) is a rare disease that involves the triad: fibrous dysplasia of bone, cutaneous cafe-au-lait spots, and precocious puberty (PP). Fibrous dysplasia is almost always present in all cases of MAS and may be either monostotic (single skeletal site involvement) or polyostotic (multiple skeletal site involvement). Although cafe-au-lait spots are often the presenting feature of MAS (present since birth or shortly after), patients with MAS usually present with complaints of either fibrous dysplasia (bone pain, limp, or pathological fracture) or precocious puberty (vaginal spotting or bleeding or early development of breast and/or pubic hair). The radiographic appearance of bone lesions in fibrous dysplasia are characteristic. Similar to the vignette, radiographs may reveal typical expansile lesions (polyostotic fibrous dysplasia) is a genetic disorder of bones, skin pigmentation, and hormonal problems characterized by precocious puberty, unilateral cafe au lait spots, and polyostotic fibrous dysplasia. The syndrome can develop at a broad spectrum of severity. McCune-Albright syndrome frequently involves the cranium and facial bones, pelvis, spine, and shoulder girdle. The sites of involvement are the femur (91%), tibia (81%), pelvis (78%), ribs, skull and facial bones (50%), upper extremities, lumbar spine, clavicle, and cervical spine, in decreasing order of frequency. The craniofacial pattern of the disease occurs in 50% of patients with the polyostotic form of fibrous dysplasia. Educational Objective: McCune-Albright syndrome (polyostotic fibrous dysplasia) is a genetic disorder of bones, skin pigmentation, and hormonal problems characterized by precocious puberty, unilateral cafe au lait spots, and polyostotic fibrous dysplasia. References: First Aid 2014 page 616]]
Approved	Approved::Yes
Keyword	WBRKeyword::McCune-Albright syndrome, WBRKeyword::Endocrine, WBRKeyword::Endocrinology, WBRKeyword::Genetics, WBRKeyword::Mosaicism, WBRKeyword::Somatic
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