Molecular and Clinical Characteristics of the McCune–Albright Syndrome

Abstract

The McCune–Albright syndrome (MAS) is characterized by the clinical triad of polyostotic fibrous dysplasia, café-au-lait pigmented skin lesions, and endocrinopathy. MAS is due to postzygotic mutation of the GNAS gene that leads to activation of Gα‎s, the alpha chain of the heterotrimeric G protein, Gs. Cells that carry the activating GNAS mutation, termed gsp, are distributed in a mosaic pattern, and the extent of the distribution of mutation-bearing cells is based on the timing of the mutational event. Thus, gsp mutations that occur late in development can cause mono-ostotic fibrous dysplasia or an isolated endocrine lesion, whereas earlier mutational events lead to widespread distribution of lesional cells and MAS. Molecular studies now enable the detection of somatic GNAS mutations in circulating cells from most patients with MAS as well as many patients who have only one affected tissue, and therefore diagnosis of MAS continues to rely upon clinical assessment.