RASopathies: The musculoskeletal consequences and their etiology and pathogenesis

The RASopathies comprise an ever-growing number of clinical syndromes resulting from germline mutations in components of the RAS/MAPK signaling pathway. While multiple organs and tissues may be affected by these mutations, this review will focus on how these mutations specifically impact the musculoskeletal system. Herein, we review the genetics and musculoskeletal phenotypes of these syndromes in humans. We discuss how mutations in the RASopathy syndromes have been studied in translational mouse models. Finally, we discuss how signaling molecules within the RAS/MAPK pathway are involved in normal and abnormal bone biology in the context of osteoblasts, osteoclasts and chondrocytes.

Automated summary

The RASopathies are clinical syndromes resulting from germline mutations in components of the RAS/MAPK signaling pathway, affecting multiple organs and tissues. This review focuses on how these mutations impact the musculoskeletal system in humans and discusses their genetics and phenotypes in both human and mouse models. It also explores the role of signaling molecules within the RAS/MAPK pathway in normal and abnormal bone biology.