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Endocr Rev. 2018 Oct 1;39(5):676-700. doi: 10.1210/er.2017-00232.

The RASopathy Family: Consequences of Germline Activation of the RAS/MAPK Pathway.

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INSERM UMR 1048, Institute of Cardiovascular and Metabolic Diseases (I2MC), University of Toulouse Paul Sabatier, Toulouse, France.
Endocrine, Bone Diseases, and Genetics Unit, Children's Hospital, Toulouse University Hospital, Toulouse, France.


Noonan syndrome [NS; Mendelian Inheritance in Men (MIM) #163950] and related syndromes [Noonan syndrome with multiple lentigines (formerly called LEOPARD syndrome; MIM #151100), Noonan-like syndrome with loose anagen hair (MIM #607721), Costello syndrome (MIM #218040), cardio-facio-cutaneous syndrome (MIM #115150), type I neurofibromatosis (MIM #162200), and Legius syndrome (MIM #611431)] are a group of related genetic disorders associated with distinctive facial features, cardiopathies, growth and skeletal abnormalities, developmental delay/mental retardation, and tumor predisposition. NS was clinically described more than 50 years ago, and disease genes have been identified throughout the last 3 decades, providing a molecular basis to better understand their physiopathology and identify targets for therapeutic strategies. Most of these genes encode proteins belonging to or regulating the so-called RAS/MAPK signaling pathway, so these syndromes have been gathered under the name RASopathies. In this review, we provide a clinical overview of RASopathies and an update on their genetics. We then focus on the functional and pathophysiological effects of RASopathy-causing mutations and discuss therapeutic perspectives and future directions.

[Indexed for MEDLINE]

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