title: Rasopathies - dysmorphic syndromes with short stature and risk of malignancy.
abstract: OBJECTIVE
  The term ´Rasopathies´ represents a group of five neurodevelopmental syndromes (Noonan, LEOPARD, Costello, Cardio-facio-cutaneous, and Neurofibromatose-Noonan syndrome) caused by germline mutation in genes encoding proteins involved in RAS/MAPK (rat sarcoma/mitogen-activated protein kinase) signaling pathway. The RAS/MAPK signaling pathway participates in regulation of cell determination, proliferation, differentiation, migration, and senescence and dysregulation of this pathway can lead to the risk of tumorigenesis. In this review, we aim to summarize the current clinical and molecular genetic knowledge on Rasopathies with special attention for the risk of cancer. We propose also clinical and therapeutic approach for patients with malignancy.
  
  
  METHODS
  We are reviewing the clinical and molecular basis of Rasopathies based on recent studies, clinical examination, and molecular diagnostics (mutation analysis of causal genes for Rasopathies) in Slovak pediatric patients.
  
  
  RESULTS
  Some clinical features, such as short stature, a specific facial dysmorphology and cardiac abnormalities are common to all of Rasopathy syndromes. However, there are unique signs by which the syndromes can differ from each other, especially multiple lentigo in LEOPARD syndrome, increased risk of malignancy in Costello syndrome, dry hyperkeratotic skin in patients with cardio-facio-cutaneous syndrome, and neurofibromas and cafe-au-lait spots in neurofibromatosis-Noonan syndrome.
  
  
  CONCLUSIONS
  Despite the overlapping clinical features, Rasopathy syndromes exhibit unique fenotypical features and the precise molecular diagnostics may lead to confirmation of each syndrome. The molecular diagnostics may allow the detection of pathogenic mutation associated with tumorigenesis.
authors.forename: M
authors.initials: M
authors.lastname: Cizmarova
authors.forename: L
authors.initials: L
authors.lastname: Kostalova
authors.forename: Z
authors.initials: Z
authors.lastname: Pribilincova
authors.forename: Z
authors.initials: Z
authors.lastname: Lasabova
authors.forename: A
authors.initials: A
authors.lastname: Hlavata
authors.forename: L
authors.initials: L
authors.lastname: Kovacs
authors.forename: D
authors.initials: D
authors.lastname: Ilencikova
mesh_terms: D001827:Body Height / Q000235:genetics; D056685:Costello Syndrome / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D004476:Ectodermal Dysplasia / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D019066:Facies; D005183:Failure to Thrive / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D006330:Heart Defects, Congenital / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D009369:Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D017253:Neurofibromatoses / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D009634:Noonan Syndrome / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors; D018631:ras Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D018631:ras Proteins