cranium and first cervical vertebrae (arrow head) enlarged by osseous fibrous dysplasia. A pituitary tumour is apparent (arrow). We diagnosed McCune-Albright ...
ARTICLES
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Clinical picture: Fuel on the fire Gabriel I Uwaifo, Pamela G Robey, Sunday O Akintoye, Michael T Collins
A 30-year-old man presented with a history of recurrent fractures and progressive facial deformity. He had café-au-lait spots at birth, and at the age of 7, sustained a pathological fracture of the proximal femur, and developed precocious puberty. He was then lost to follow-up for more than 20 years. On examination he had asymmetrical macrocrania, frontal bossing, right optic nerve atrophy, hypertelorism, and prognathism. Magnetic resonance imaging of the brain showed a cranium and first cervical vertebrae (arrow head) enlarged by osseous fibrous dysplasia. A pituitary tumour is apparent (arrow). We diagnosed McCune-Albright syndrome, a rare disease defined by the triad of café-au-lait skin spots, precocious puberty, and polyostotic fibrous dysplasia. Other findings are renal phosphate wasting and the hyperfunctioning endocrinopathies: hyperthyroidism, acromegaly (as in this case), and Cushing's syndrome. Fibrous dysplasia in the craniofacial region is exacerbated by growth hormone excess, adding fuel to the fire. The underlying genetic defect consists of post-zygotic activating mutations in the GNAS1 gene, which codes for the ␣ subunit of the signalling G protein (Gs␣). The activating mutations in GS␣ result in ligand-independent activation of the cAMP signalling pathway and lead to cellular hyperfunction, and in some cases, hyperplasia. As the mutation is post-zygotic, the patients are phenotypically somatic mosaics. Developmental Endocrinology Branch (G I Uwaifo MBBS) and Craniofacial and Skeletal Diseases Branch (P G Robey PhD, S O Akintoye DDS, M T Collins MD), National Institutes of Health, Bethesda, MD 20892-4320, USA
THE LANCET • Vol 357 • June 23, 2001
2011
For personal use only. Reproduce with permission from The Lancet Publishing Group.
