Development of International Guidelines for the Care of Fibrous Dysplasia/McCune-Albright Syndrome

Presentation Number: MON 340
Date of Presentation: April 3rd, 2017

Alison M Boyce*1, Roland Chapurlat2, Neveen A.T. Hamdy3, Natasha M Appelman-Dijkstra3, Maria Luisa Brandi4, Muhammad K Javaid5 and Michael T. Collins1
1Section on Skeletal Disorders and Mineral Homeostasis, Bethesda, MD, 2INSERM UMR 1033, Université de Lyon, Hôpital Edouard Herriot, Lyon, France, 3Leiden University Medical Center, Leiden, Netherlands, 4University of Florence, Florence, Italy, 5University of Oxford

Abstract

Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a rare disorder caused by post-zygotic activating mutations in GNAS, which encodes the α-subunit of the Gs signaling protein and leads to dysregulated cyclic AMP signaling in affected tissues. The disease is classically defined by the triad of skeletal lesions, pigmented skin macules, and hyperfunctioning endocrinopathies, however the centrality of Gs signaling in most organ systems allows for the potential for a broad and complex phenotype. FD may involve one bone (monostotic) or multiple (polyostotic), and may occur in isolation or in combination with extraskeletal disease. Any part or combination of features may be present.

Clinical management in FD/MAS is challenging, and multiple barriers exist to providing consistent, high quality care. Some of these include the broad clinical spectrum which results in considerable phenotypic variability among patients; multisystem involvement which requires coordination between diverse specialists; and disease rarity, which makes it challenging for individual clinicians and centers to gain particular expertise. Knowledge gaps in FD/MAS pathophysiology and natural history, as well as the paucity of clinical trials, add further difficulty for clinicians caring for patients with FD/MAS.

To address these challenges, an international consortium of clinicians, researchers, and advocates with extensive experience in FD/MAS was established to develop a comprehensive set of diagnostic and treatment guidelines. The approach was to synthesize existing literature with clinical expertise in FD/MAS to establish best practices for diagnosis, staging, treatment, and monitoring. The resulting consensus guidelines will serve as a road map for clinicians, advocacy groups, and patients to identify international standard of care practices in patients with FD/MAS, and to establish historical controls for future clinical studies.

 

Disclosure: RC: Research Funding, Chugai-Roche. MLB: Investigator, NPS-Shire, Speaker Bureau Member, NPS-Shire. Nothing to Disclose: AMB, NATH, NMA, MKJ, MTC