Rasopathies - dysmorphic syndromes with short stature and risk of malignancy
- PMID: 24156711
- DOI: 10.4149/endo_2013_04_217
Rasopathies - dysmorphic syndromes with short stature and risk of malignancy
Abstract
Objectives: 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.
Conclusion: 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.
Similar articles
-
Objective studies of the face of Noonan, Cardio-facio-cutaneous, and Costello syndromes: A comparison of three disorders of the Ras/MAPK signaling pathway.Am J Med Genet A. 2016 Oct;170(10):2570-7. doi: 10.1002/ajmg.a.37736. Epub 2016 May 7. Am J Med Genet A. 2016. PMID: 27155212
-
A review of craniofacial and dental findings of the RASopathies.Orthod Craniofac Res. 2017 Jun;20 Suppl 1(Suppl 1):32-38. doi: 10.1111/ocr.12144. Orthod Craniofac Res. 2017. PMID: 28643916 Free PMC article. Review.
-
Peripheral muscle weakness in RASopathies.Muscle Nerve. 2012 Sep;46(3):394-9. doi: 10.1002/mus.23324. Muscle Nerve. 2012. PMID: 22907230
-
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. Dev Period Med. 2014. PMID: 25182392 Review.
-
Senescence in RASopathies, a possible novel contributor to a complex pathophenoype.Mech Ageing Dev. 2021 Mar;194:111411. doi: 10.1016/j.mad.2020.111411. Epub 2020 Dec 9. Mech Ageing Dev. 2021. PMID: 33309600 Review.
Cited by
-
Non-Mammalian Models for Understanding Neurological Defects in RASopathies.Biomedicines. 2024 Apr 10;12(4):841. doi: 10.3390/biomedicines12040841. Biomedicines. 2024. PMID: 38672195 Free PMC article. Review.
-
Case report: The cardio-facio-cutaneous syndrome due to a novel germline mutation in MAP2K1: A multifaceted disease with immunodeficiency and short stature.Front Pediatr. 2022 Oct 14;10:990111. doi: 10.3389/fped.2022.990111. eCollection 2022. Front Pediatr. 2022. PMID: 36313893 Free PMC article.
-
Integrated in silico MS-based phosphoproteomics and network enrichment analysis of RASopathy proteins.Orphanet J Rare Dis. 2021 Jul 6;16(1):303. doi: 10.1186/s13023-021-01934-x. Orphanet J Rare Dis. 2021. PMID: 34229750 Free PMC article.
-
Modeling the developmental origins of pediatric cancer to improve patient outcomes.Dis Model Mech. 2021 Feb 22;14(2):dmm048930. doi: 10.1242/dmm.048930. Dis Model Mech. 2021. PMID: 33619212 Free PMC article. Review.
-
Craniofacial and cutaneous findings in Noonan, Costello and LEOPARD syndromes.Postepy Dermatol Alergol. 2018 Oct;35(5):437-441. doi: 10.5114/pdia.2017.70330. Epub 2018 Jul 19. Postepy Dermatol Alergol. 2018. PMID: 30429698 Free PMC article. Review.
Publication types
MeSH terms
Substances
Supplementary concepts
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials