Skeletal Disorders and Mineral Homeostasis Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA.
Musculoskeletal Research Unit, Hospital del Mar Institute of Medical Investigation (IMIM), Barcelona, Spain.
Eur J Endocrinol. 2020 May;182(5):R83-R99. doi: 10.1530/EJE-19-0969.
Fibrous dysplasia/McCune-Albright Syndrome (FD/MAS), arising from gain-of-function mutations in Gαs, and cutaneous skeletal hypophosphatemia syndrome (CSHS), arising from gain-of-function mutations in the Ras/MAPK pathway, are strikingly complex, mosaic diseases with overlapping phenotypes. Both disorders are defined by mosaic skin and bone involvement, and both are complicated by increased FGF23 production. These similarities have frequently led to mis-diagnoses, primarily in patients with CSHS who are often assumed to have FD/MAS. The intriguing similarities in skeletal involvement in these genetically distinct disorders have led to novel insights into FGF23 physiology, making an understanding of FD/MAS and CSHS relevant to both clinicians and researchers interested in bone and endocrine disorders. This review will give an overview of FD/MAS and CSHS, focusing on the roles of mosaicism and FGF23 in the pathogenesis and clinical presentation of these disorders.
纤维结构不良/ McCune-Albright 综合征（FD/MAS），由 Gαs 的功能获得性突变引起，以及皮肤骨骼低磷血症综合征（CSHS），由 Ras/MAPK 通路的功能获得性突变引起，都是非常复杂的镶嵌性疾病，具有重叠的表型。这两种疾病都以镶嵌性皮肤和骨骼受累为特征，并且都伴有成纤维细胞生长因子 23（FGF23）产生增加。这些相似之处经常导致误诊，主要是在 CSHS 患者中，他们经常被误诊为 FD/MAS。这些在遗传上不同的疾病中骨骼受累的惊人相似之处，为 FGF23 的生理学提供了新的见解，使人们对 FD/MAS 和 CSHS 的理解与对骨骼和内分泌疾病感兴趣的临床医生和研究人员相关。这篇综述将概述 FD/MAS 和 CSHS，重点介绍镶嵌性和 FGF23 在这些疾病发病机制和临床表现中的作用。
