The musculoskeletal phenotype of the RASopathies

David A. Stevenson, Feng Chun Yang

Research output: Contribution to journalArticle

29 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)90-103
Number of pages14
JournalAmerican Journal of Medical Genetics, Part C: Seminars in Medical Genetics
Volume157
Issue number2
DOIs
StatePublished - May 15 2011
Externally publishedYes

Keywords

  • Bone
  • Cardiofaciocutaneous syndrome
  • Costello syndrome
  • NF1
  • Noonan syndrome

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'The musculoskeletal phenotype of the RASopathies'. Together they form a unique fingerprint.

  • Cite this