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In MAS, a syndrome classically characterized by polyostotic fibrous dysplasia (FD), caf\u00e9\u2010au\u2010lait (CAL) skin spots, and precocious puberty, the heterogenity of organ involvement, age of onset, and clinical severity of the disease are thought to reflect the variable size and the random distribution of the mutated cell clone arising from the postzygotic mutation. We report a case of neonatal MAS with hypercortisolism and cholestatic hepatobiliary dysfunction in which bone changes indirectly emanating from the disease genotype, and distinct from FD, led to a fatal outcome. Pulmonary embolism of marrow and bone fragments secondary to rib fractures was the immediate cause of death. Ribs, and all other skeletal segments, were free of changes of typical FD and fractures appeared to be the result of a mild\u2010to\u2010moderate degree of osteopenia. The mutated allele was abundant in the adrenal glands and liver, but not in skin, muscle, and fractured ribs, where it could only be demonstrated using a much more sensitive PNA hybridization probe\u2010based FRET (F\u00f6rster resonance energy transfer) technique. Histologically, bilateral adrenal hyperplasia and cholestatic disease matched the abundant disease genotype in the adrenals and liver. Based on this case and other sporadic reports, it appears that gain\u2010of\u2010function mutations of\n                      <jats:italic>GNAS<\/jats:italic>\n                      underlie a unique syndromic profile in neonates characterized by CAL skin spots, hypercortisolism, hyperthyroidism, hepatic and cardiac dysfunction, and an absence (or latency) of FD, often with a lethal outcome. Taken together, our and previous cases highlight the phenotypic severity and the diagnostic and therapeutic challenges of MAS in neonates. Furthermore, our case specifically points out how secondary bone changes, unrelated to the direct impact of the mutation, may contribute to the unfavorable outcome of very early\u2010onset MAS. \u00a9 2018 The Authors\n                      <jats:italic>JBMR Plus<\/jats:italic>\n                      published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jbm4.10134","type":"journal-article","created":{"date-parts":[[2018,12,14]],"date-time":"2018-12-14T21:00:32Z","timestamp":1544821232000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Neonatal McCune\u2010Albright Syndrome: A Unique Syndromic Profile With an Unfavorable Outcome"],"prefix":"10.1093","volume":"3","author":[{"given":"Alessandro","family":"Corsi","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine Sapienza University Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha","family":"Cherman","sequence":"additional","affiliation":[{"name":"Skeletal Biology Section National Institute of Dental and Craniofacial Research National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L","family":"Donaldson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Utah, School of Medicine Salt Lake City UT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela G","family":"Robey","sequence":"additional","affiliation":[{"name":"Skeletal Biology Section National Institute of Dental and Craniofacial Research National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael T","family":"Collins","sequence":"additional","affiliation":[{"name":"Skeletal Disorders and Mineral Homeostasis Section National Institute of Dental and Craniofacial Research National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara","family":"Riminucci","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine Sapienza University Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,1,15]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199112123252403"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.11.5152"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(05)80943-6"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0303-7207(98)00116-6"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2000.15.1.120"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004280000217"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/mp.55.1.58"},{"key":"e_1_2_8_9_1","doi-asserted-by":"crossref","unstructured":"BiancoP RobeyPG WientroubS. 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