A 12-year-old girl has a limp and shortening of the left lower limb. X-ray shows an expansile lesion of the proximal femur with a typical ground-glass matrix and a varus deformity producing the 'shepherd's crook' shape. She also has cafe-au-lait macules with irregular ('coast of Maine') borders and history of precocious puberty. The underlying genetic abnormality is:

• A Amplification of the MDM2 gene
• B Translocation t(11;22) forming EWS-FLI1 fusion
• C Mutation of TP53 tumour suppressor gene
• D Mutation of the GNAS gene activating Gs alpha ✓

Explanation

Polyostotic fibrous dysplasia with cafe-au-lait spots and endocrine hyperfunction such as precocious puberty defines McCune-Albright syndrome, caused by a postzygotic activating mutation of GNAS encoding the Gs alpha subunit, leading to constitutive cAMP signalling. Ground-glass matrix and shepherd's crook deformity are the radiological hallmarks of fibrous dysplasia. EWS-FLI1 relates to Ewing sarcoma and MDM2 amplification to liposarcoma.

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.