A 14-year-old girl has painless swelling of the proximal femur. X-ray shows a well-defined radiolucent lesion with a ground glass matrix and no periosteal reaction, with thinning of the overlying cortex. She also has café au lait macules and precocious puberty. Biopsy shows curvilinear trabeculae of woven bone arising directly in a fibrous stroma without osteoblastic rimming. Mutation of which gene explains this constellation?

• A EXT1
• B APC
• C TP53
• D GNAS ✓

Explanation

Fibrous dysplasia with polyostotic bone lesions, café au lait spots, and endocrine hyperfunction such as precocious puberty defines McCune Albright syndrome, caused by postzygotic activating GNAS mutations. The mutation raises cAMP in affected tissues. The ground glass radiology and woven bone lacking osteoblastic rimming confirm fibrous dysplasia, while EXT1 causes multiple osteochondromas.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.