Fibrous dysplasia/McCune-Albright syndrome: a rare, mosaic disease of G αs activation.

Fibrous dysplasia/McCune-Albright syndrome: a rare, mosaic disease of Gαs activation. Endocr Rev. 2019 Nov 01;: Authors: Boyce AM, Collins MT Abstract Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a rare disorder of striking complexity. It arises from somatic, gain-of-function mutations in GNAS, leading to mosaic Gαs activation and inappropriate production of intracellular cyclic adenosine monophosphate (AMP). The clinical phenotype is largely determined by the location and extent of affected tissues, and the pathophysiologic effects of Gαs activation within these tissues. In bone, Gαs activation results in impaired differentiation of skeletal stem cells, leading to discrete skeletal lesions prone to fracture, deformity, and pain. Extraskeletal manifestations include a variable combination of hyperpigmented macules and hyperfunctioning endocrinopathies. Distinctive age-related changes in disease development has key effects on histologic, radiographic, and clinical features. FD/MAS thus presents along a uniquely broad clinical spectrum, and the resulting challenges in diagnosis and management can be difficult for clinicians. This review presents FD/MAS in the context of a mosaic disorder of Gαs activation, providing an intellectual framework within which to understand, evaluate, and treat this interesting disease. It includes a comprehensive summary of current understanding of FD/MAS pathogenesis, and a detailed discussi...
Source: ENDOCR REV - Category: Endocrinology Authors: Tags: Endocr Rev Source Type: research