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The musculoskeletal phenotype of the RASopathies
Author(s) -
Stevenson David A.,
Yang FengChun
Publication year - 2011
Publication title -
american journal of medical genetics part c: seminars in medical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.419
H-Index - 101
eISSN - 1552-4876
pISSN - 1552-4868
DOI - 10.1002/ajmg.c.30296
Subject(s) - costello syndrome , noonan syndrome , neurofibromatosis , phenotype , mapk/erk pathway , scoliosis , medicine , osteopenia , dysplasia , signal transduction , ptpn11 , kyphosis , cancer research , genetics , biology , pathology , bioinformatics , mutation , gene , osteoporosis , bone mineral , radiography , kras , radiology
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. © 2011 Wiley‐Liss, Inc.