[Noonan syndrome: genetic and clinical update and treatment options].

Abstract

Noonan syndrome (NS) is a relatively common genetic condition characterised by short stature, congenital heart defects, and distinctive facial features. NS and other clinically overlapping conditions such as NS with multiple lentigines (formerly called LEOPARD syndrome), cardiofaciocutaneous syndrome, or Costello syndrome, are caused by mutations in genes encoding proteins of the RAS-MAPKinases pathway. Because of this shared mechanism, these conditions have been collectively termed «RASopathies». Despite the recent advances in molecular genetics, nearly 20% of patients still lack a genetic cause, and diagnosis is still made mainly on clinical grounds. NS is a clinically and genetically heterogeneous condition, with variable expressivity and a changing phenotype with age, and affects multiple organs and systems. Therefore, it is essential that physicians involved in the care of these patients are familiarised with their manifestations and the management recommendations, including management of growth and development. Data on growth hormone treatment efficacy are sparse, and show a modest response in height gains, similar to that observed in Turner syndrome. The role of RAS/MAPK hyper-activation in the pathophysiology of this group of disorders offers a unique opportunity for the development of targeted approaches.

• Authors: Atilano Carcavilla, Larisa Suárez-Ortega, Amparo Rodríguez Sánchez, Isabel Gonzalez-Casado, Marta Ramón-Krauel, Jose Ignacio Labarta, Sofia Quinteiro Gonzalez, Isolina Riaño Galán, Begoña Ezquieta Zubicaray, Juan Pedro López-Siguero
• Journal: Anales de pediatria (An Pediatr (Engl Ed)) Vol. 93 Issue 1 Pg. 61.e1-61.e14 (Jul 2020) ISSN: 2341-2879 [Electronic] Spain
• Vernacular Title: Síndrome de Noonan: actualización genética, clínica y de opciones terapéuticas.
• PMID: 32493603 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Chemical References

• Genetic Markers
• Mitogen-Activated Protein Kinases
• Proto-Oncogene Proteins p21(ras)

Topics

• Diagnosis, Differential
• Genetic Markers
• Genotype
• Humans
• Mitogen-Activated Protein Kinases (genetics)
• Mutation
• Noonan Syndrome (diagnosis, genetics, physiopathology, therapy)
• Phenotype
• Proto-Oncogene Proteins p21(ras) (genetics)