title: Fibrous Dysplasia/McCune-Albright Syndrome: Clinical and Translational Perspectives.
abstract: Fibrous dysplasia (FD) is an uncommon and debilitating skeletal disorder resulting in fractures, deformity, functional impairment, and pain. It arises from post-zygotic somatic activating mutations in GNAS, in the cAMP-regulating transcript α-subunit, Gsα. Constitutive Gs signaling results in activation of adenylyl cyclase and dysregulated cAMP production. In the skeleton, this leads to the development of FD lesions with abnormal bone matrix, trabeculae, and collagen, produced by undifferentiated mesenchymal cells. FD may occur in isolation or in combination with extraskeletal manifestations, including hyperfunctioning endocrinopathies and café-au-lait macules, termed McCune-Albright syndrome (MAS). This review summarizes current clinical and translational perspectives in FD/MAS, with an emphasis on FD pathogenesis, natural history, pre-clinical and clinical investigation, and future directions.
authors: Section on Skeletal Disorders and Mineral Homeostasis, Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, 30 Convent Drive Room 228 MSC 4320, Bethesda, MD, 20892, USA.
authors: Cemre
authors: C
authors: Robinson
authors: Section on Skeletal Disorders and Mineral Homeostasis, Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, 30 Convent Drive Room 228 MSC 4320, Bethesda, MD, 20892, USA.
authors: Michael T
authors: MT
authors: Collins
authors: Section on Skeletal Disorders and Mineral Homeostasis, Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, 30 Convent Drive Room 228 MSC 4320, Bethesda, MD, 20892, USA. boyceam@mail.nih.gov.|Division of Endocrinology and Diabetes, Children's National Health System, Washington, DC, USA. boyceam@mail.nih.gov.|Bone Health Program, Division of Orthopaedics and Sports Medicine, Children's National Health System, Washington, DC, USA. boyceam@mail.nih.gov.
authors: Alison M
authors: AM
authors: Boyce
mesh_terms: D000818:Animals; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D002864:Chromogranins / Q000235:genetics*; D004195:Disease Models, Animal; D000089703:Fibroblast Growth Factor-23; D005357:Fibrous Dysplasia of Bone / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D005359:Fibrous Dysplasia, Polyostotic / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D006801:Humans; D059408:Pain Management; D057170:Translational Research, Biomedical
chemical_list: D050071:Bone Density Conservation Agents; D002864:Chromogranins; C000717427:FGF23 protein, human; D000089703:Fibroblast Growth Factor-23; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs
keywords: FGF23; Fibrous dysplasia; GNAS gene; Gsα; McCune-Albright syndrome