title: The musculoskeletal phenotype of the RASopathies.
abstract: The Ras/MAPK signal transduction pathway is critical for the regulation of proliferation and differentiation of multiple cell types. Neurofibromatosis type 1 (NF1) is caused by inactivating mutations in the NF1 gene resulting in an increased Ras signaling cascade. Subsequently, additional syndromes with some overlapping physical manifestations such as Noonan syndrome, Costello syndrome, and cardiofaciocutaneous (CFC) syndrome were also shown to be due in many cases to mutations in genes encoding for proteins interacting with the Ras/MAPK pathway. Although neurocutaneous manifestations have been considered hallmark features for these disorders, multiple organ systems including the musculoskeletal system are affected. Some of the overlapping musculoskeletal phenotypes include scoliosis, kyphosis, anterior chest wall anomalies, pes planus, osteopenia, and hand anomalies. However, there are also discordant skeletal phenotypes such as sphenoid wing dysplasia and tibial pseudarthrosis seen only in NF1. We provide an overview of the concordant and discordant musculoskeletal manifestations in the RASopathies.
authors.affiliation: Division of Medical Genetics, University of Utah, Salt Lake City, UT 84132, USA. david.stevenson@hsc.utah.edu
authors.forename: David A
authors.initials: DA
authors.lastname: Stevenson
authors.forename: Feng-Chun
authors.initials: FC
authors.lastname: Yang
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000166:cytology / Q000503:physiopathology*; D030342:Genetic Diseases, Inborn / Q000235:genetics / Q000473:pathology*; D006801:Humans; D051379:Mice; D009141:Musculoskeletal System / Q000473:pathology*; D010641:Phenotype; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D013577:Syndrome
chemical_list: D016283:Proto-Oncogene Proteins p21(ras)