Snapshot A 7-year-old girl is brought to the pediatrician by her mother due to vaginal bleeding. The mother reports that her daughter appears happy, playful, and does exceptionally well in school. The mother says that she is in a healthy relationship with her husband, and the patient is an only child. The mother also states that the daughter reports pain "in her bones" and "stiffness." On physical exam, the patient is conversational and not shy. There is tenderness to palpation of the lower extremities and a hyperpigmented spot with ragged edges on the left leg. Breast development is noted, and there is mild blood in the vaginal introitus without trauma to the external and internal vagina. The patient is referred to a pediatric endocrinologist. Introduction Clinical definition a rare genetic disorder characterized by polyostotic fibrous dysplasia café-au-lait spots endocrinopathy classically with precocious puberty others include hyperthyroidism, infantile Cushing syndrome, gigantism, and acromegaly Epidemiology incidence precocious puberty is more common in females demographics early childhood Pathogenesis activating mutation in GNAS1 leads to overproduction of downsteam proteins Genetics inheritance pattern autosomal recessive mutation postzygotic mosaic somatic activating mutation in GNAS1 on chromosome 20 GNAS1 codes for a Gsα involved in G-protein signaling Presentation Symptoms precocious puberty vaginal bleeding or breast development without pubic hair growth typically occurs at an earlier age than normal bone pain joint stiffness Physical exam café-au-lait spots no family history pathologic fractures visible bone deformities may be found Imaging Radiographs indication involved in the work-up of bone involvement (e.g., fracture) findings patchy areas of lytic bone lesions and sclerosis more commonly in the metaphyseal and diaphyseal regions trabeculated lesions with a ground-glass appearance may be found Studies Labs molecular testing for GNAS1 analysis Differential Neurofibromatosis type I has neurologic involvement and a family history of café-au-lait spots Treatment There are no specific treatments for McCune-Albright syndrome treatment is aimed at the complications of this genetic disorder Complications Increased risk for fracture