Severe endocrine and nonendocrine manifestations of the McCune-Albright syndrome associated with activating mutations of stimulatory G protein Gs

Andrew Shenker, Lee S. Weinstein, Antoinette Moran, Ora H. Pescovitz, Nancy J. Charest, Charlotte M. Boney, Judson J. Van Wyk, Maria J. Merino, Penelope P. Feuillan, Allen M. Spiegel

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251 Scopus citations

Abstract

McCune-Albright syndrome (MCAS) is a sporadic disease classically includingpolyostotic fibrous dysplasia, café au lait spots, sexual precocity, and other hyperfunctional endocrinopathies. An activating missense mutation in the gene for the alpha subunit of GS, the G protein that stimulates cyclic adenosine monophosphate formation, has been reported to be present in these patients. The mutation is found in variable abundance in different affected endocrine and nonendocrine tissues, consistent with the mosaic distribution of abnormal cells generated by a somatic cell mutation early in embryogenesis. We describe three patients with MCAS who had profound endocrine and nonendocrine disease and who died in childhood. Two of the patients were severely ill neonates whose complex symptoms did not immediately suggest MCAS. A mutation of residue Arg201 of GSα was found in affected tissues from all three children. A review of the literature and unpublished case histories emphasizes the existence of other patients with severe and unusual clinical manifestations. We conclude that the manifestations of MCAS are more extensive than is generally appreciated, and may include hepatobiliary disease, cardiac disease, other nonendocrine abnormalities, and sudden or premature death.

Original languageEnglish (US)
Pages (from-to)509-518
Number of pages10
JournalThe Journal of Pediatrics
Volume123
Issue number4
DOIs
Publication statusPublished - Oct 1993
Externally publishedYes

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ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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