Snapshot A 6-year-old girl presents to the pediatrician with her mother due to the presence of vaginal bleeding. The mother said she began menarche at 14 years of age and the patient's older sister at 15. The mother is in a healthy relationship with her husband and reports that the patient has been complaining of bone pain and stiffness in her legs. On physical exam, the patient is happy, playful, and conversational. There is tenderness to palpation in her bilateral lower extremities, as well as a hyperpigmented spot with ragged edges. There is mild blood in the vaginal introitus with no evidence of vaginal trauma. 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 Etiology Pathogenesis activating mutation in GNAS1 leads to overproduction of downstream proteins Genetics inheritance pattern autosomal recessive mutation postzygotic 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