David A. Stevenson, M.D. is an Assistant Professor of Pediatrics in the Division of Medical Genetics at the University of Utah School of Medicine. Dr. Stevenson's research interests focus on bone remodeling and understanding genotype–phenotype correlations of disorders of the Ras/MAPK pathway. Dr. Stevenson is supported by the Thrasher Research Fund, and a Doris Duke Charitable Foundation Clinical Scientist Development Award.
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Article
The musculoskeletal phenotype of the RASopathies†
Article first published online: 14 APR 2011
DOI: 10.1002/ajmg.c.30296
Copyright © 2011 Wiley-Liss, Inc.
Issue
American Journal of Medical Genetics Part C: Seminars in Medical Genetics
Special Issue: Disorders of the Ras Pathway
Volume 157, Issue 2, pages 90–103, 15 May 2011
Additional Information
How to Cite
Stevenson, D. A. and Yang, F.-C. (2011), The musculoskeletal phenotype of the RASopathies. American Journal of Medical Genetics Part C: Seminars in Medical Genetics, 157: 90–103. doi: 10.1002/ajmg.c.30296
- †
How to Cite this Article: Stevenson DA, Yang F-C. 2011. The musculoskeletal phenotype of the RASopathies. Am J Med Genet Part C Semin Med Genet 157:90–103.
Publication History
- Issue published online: 19 APR 2011
- Article first published online: 14 APR 2011
- Abstract
- Article
- References
- Cited By
Keywords:
- bone;
- cardiofaciocutaneous syndrome;
- NF1;
- Costello syndrome;
- Noonan syndrome
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. © 2011 Wiley-Liss, Inc.