MCCUNE-ALBRIGHT SYNDRÓM

Activating or gain-of-function GNAS1 mutations in patients with the McCune-Albright syndrome (https://omim.org/entry/174800) are present in the mosaic state, resulting from a postzygotic somatic mutation appearing early in the course of development which yields a monoclonal population of mutated cells within variously affected tissues. The nonmosaic state for most activating mutations is presumably lethal to the embryo. The disorder is characterized clinically by the classic triad of polyostotic fibrous dysplasia (POFD), cafe-au-lait skin pigmentation, and peripheral precocious puberty. However, the disorder is clinically heterogeneous and can include various other endocrinologic anomalies such as thyrotoxicosis, pituitary gigantism, and Cushing syndrome (219080) (Lumbroso et al., 2004).