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It is due to heterozygous mutations in <jats:italic>BRAF, MAP2K1, MAP2K2<\/jats:italic>, and <jats:italic>KRAS<\/jats:italic> genes, belonging to the RAS\/MAPK pathway. The role of RAS signaling in bone homeostasis is highly recognized, but data on bone mineral density (BMD) in CFCS are lacking. In the present study we evaluated bone parameters, serum and urinary bone metabolites in 14 individuals with a molecularly confirmed diagnosis of CFCS. Bone assessment was performed through dual X\u2010ray absorptiometry (DXA); height\u2010adjusted results were compared to age\u2010 and sex\u2010matched controls. Blood and urinary bone metabolites were also analyzed and compared to the reference range. Despite vitamin D supplementation and almost normal bone metabolism biomarkers, CFCS patients showed significantly decreased absolute values of DXA\u2010assessed subtotal and lumbar BMD (<jats:italic>p<\/jats:italic>\u2009\u2264\u20090.05), compared to controls. BMD <jats:italic>z<\/jats:italic>\u2010scores and <jats:italic>t<\/jats:italic>\u2010scores (respectively collected for children and adults) were below the reference range in CFCS, while normal in healthy controls. These findings confirmed a reduction in BMD in CFCS and highlighted the importance of monitoring bone health in these affected individuals.<\/jats:p>","DOI":"10.1002\/ajmg.a.62588","type":"journal-article","created":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T12:50:08Z","timestamp":1638449408000},"page":"414-421","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Characterization of bone homeostasis in individuals affected by cardio\u2010facio\u2010cutaneous syndrome"],"prefix":"10.1002","volume":"188","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4089-637X","authenticated-orcid":false,"given":"Chiara","family":"Leoni","sequence":"first","affiliation":[{"name":"Center for Rare Diseases and Birth Defects, Department of Woman and Child Health and Public Health Fondazione Policlinico Universitario A. 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