The RASopathies as an example of RAS/MAPK pathway disturbances - clinical presentation and molecular pathogenesis of selected syndromes

Dev Period Med. 2014 Jul-Sep;18(3):285-96.

Abstract

The RASopathies are a class of developmental syndromes. Each of them exhibits distinctive phenotypic features, although there are numerous overlapping clinical manifestations that include: dysmorphic craniofacial features, congenital cardiac defects, skin abnormalities, varying degrees of intellectual disability and increased risk of malignancies. These disorders include: Noonan syndrome, Costello syndrome, LEOPARD syndrome, cardio-facio-cutaneous syndrome (CFC), capillary malformation-arteriovenous malformation syndrome (CM-AVM), Legius syndrome and neurofibromatosis type 1 (NF1). The RASopathies are associated with the presence of germline mutation in genes encoding specific proteins of the RAS/mitogen - activated protein kinase (MAPK) pathway that plays a crucial role in embryonic and postnatal development. In this review, we present the clinical and molecular features of selected syndromes from the RASopathies group.

Publication types

  • Review

MeSH terms

  • Arteriovenous Malformations / genetics*
  • Capillaries / abnormalities*
  • Costello Syndrome
  • Craniofacial Abnormalities / genetics*
  • Ectodermal Dysplasia / genetics*
  • Facies
  • Failure to Thrive / genetics*
  • Germ-Line Mutation*
  • Heart Defects, Congenital / genetics*
  • Humans
  • LEOPARD Syndrome / genetics
  • MAP Kinase Signaling System / genetics
  • Mitogen-Activated Protein Kinases / genetics*
  • Neurofibromatosis 1 / genetics*
  • Noonan Syndrome
  • Port-Wine Stain / genetics*
  • Signal Transduction / genetics
  • ras Proteins / genetics*

Substances

  • Mitogen-Activated Protein Kinases
  • ras Proteins

Supplementary concepts

  • Capillary Malformation-Arteriovenous Malformation
  • Cardiofaciocutaneous syndrome