A 4-year-old girl has large hyperpigmented macules on the trunk with jagged, irregular 'coast of Maine' borders, a large unilateral cafe-au-lait patch on the thigh, and precocious puberty. Skeletal survey shows fibrous dysplasia of the femur. The underlying molecular event is:

• A Germline NF1 mutation with loss of heterozygosity
• B Constitutional mismatch repair deficiency
• C Germline LEGUMAIN mutation
• D Postzygotic activating mutation of GNAS encoding the Gs alpha subunit ✓

Explanation

McCune-Albright syndrome arises from a postzygotic (somatic mosaic) activating GNAS mutation, producing the classic triad of polyostotic fibrous dysplasia, precocious puberty and cafe-au-lait macules. Unlike the smooth-bordered 'coast of California' macules of neurofibromatosis type 1, its macules are large, few, unilateral and have jagged coast-of-Maine borders, typically stopping at the midline. Because the mutation is mosaic and activating in a lethal germline state, it cannot be transmitted vertically.

Reference: Williams Textbook of Endocrinology, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.