scholarly journals Noonan Syndrome and Related Disorders: A Review of Clinical Features and Mutations in Genes of the RAS/MAPK Pathway

2009 ◽  
Vol 71 (4) ◽  
pp. 185-193 ◽  
Author(s):  
Alexander A.L. Jorge ◽  
Alexsandra C. Malaquias ◽  
Ivo J.P. Arnhold ◽  
Berenice B. Mendonca
Keyword(s):  
Clinical Features ◽  
Noonan Syndrome ◽  
Mapk Pathway

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

2018 ◽  
Vol 39 (5) ◽  
pp. 676-700 ◽  
Author(s):  
Mylène Tajan ◽  
Romain Paccoud ◽  
Sophie Branka ◽  
Thomas Edouard ◽  
Armelle Yart
Keyword(s):  
Noonan Syndrome ◽  
Mapk Pathway ◽  
Genetic Disorders ◽  
Mapk Signaling ◽  
Mendelian Inheritance ◽  
Disease Genes ◽  
Type I ◽  
Future Directions ◽  
Legius Syndrome ◽  
Anagen Hair

Abstract 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.

Neurofibromatosis-Noonan syndrome: Case report and clinicopathogenic review of the Neurofibromatosis-Noonan syndrome and RAS-MAPK pathway

2011 ◽  
Vol 17 (4) ◽  
Author(s):  
Irela Reig ◽  
Pablo Boixeda ◽  
Beatriz Fleta ◽  
Carmen Morenoc ◽  
Lucía Gámez ◽  
...  
Keyword(s):  
Case Report ◽  
Noonan Syndrome ◽  
Mapk Pathway

Noonan Syndrome: Clinical Features, Diagnosis, and Management Guidelines

PEDIATRICS ◽  
2010 ◽  
Vol 126 (4) ◽  
pp. 746-759 ◽  
Author(s):  
A. A. Romano ◽  
J. E. Allanson ◽  
J. Dahlgren ◽  
B. D. Gelb ◽  
B. Hall ◽  
...  
Keyword(s):  
Clinical Features ◽  
Noonan Syndrome ◽  
Management Guidelines ◽  
Diagnosis And Management

scholarly journals Co-occurrence of Noonan and Cardiofaciocutaneous Syndrome Features in a Patient with KRAS Variant

2018 ◽  
Vol 07 (04) ◽  
pp. 158-163 ◽  
Author(s):  
Carla Vallejos ◽  
Víctor Bolanos-Garcia ◽  
Diana Ponce ◽  
Nancy Unanue ◽  
Francisco Garay ◽  
...  
Keyword(s):  
Noonan Syndrome ◽  
De Novo ◽  
Mapk Pathway ◽  
Melting Curve ◽  
Melting Curve Analysis ◽  
Iranian Patient ◽  
Feeding Difficulties ◽  
Mutational Frequency ◽  
Cardiofaciocutaneous Syndrome ◽  
Sparse Hair

AbstractWe report the case of a 3-year-old girl, who is the third child of nonconsanguineous parents, with short stature, hypertrophic cardiomyopathy, and mild dysmorphic features; all suggestive of Noonan syndrome. In addition, the patient presents with feeding difficulties, deep palmar and plantar creases, sparse hair, and delayed psychomotor and language development, all characteristics frequently observed in cardiofaciocutaneous syndrome. Molecular analysis of the Ras/ MAPK pathway genes using high-resolution melting curve analysis and gene sequencing revealed a de novo KRAS amino acid substitution of leucine to tryptophan at codon 53 (p.L53W). This substitution was recently described in an Iranian patient with Noonan syndrome. The findings described in this report expand the phenotypic heterogeneity observed in RASopathy patients harboring a KRAS substitution, and advocate for the inclusion of genes with low mutational frequency in genetic screening protocols for Noonan syndrome and other RASopathies.

Andersen-Tawil syndrome: Overlapping clinical features with Noonan syndrome?

2021 ◽  
pp. 104382
Author(s):  
A.S. van der Werf - ’t Lam ◽  
A. van Haeringen ◽  
T. Rinnen ◽  
R.M. Robles de Medina ◽  
A. Wilde ◽  
...  
Keyword(s):  
Clinical Features ◽  
Noonan Syndrome

Cochlear implantation and clinical features in patients with Noonan syndrome and Noonan syndrome with multiple lentigines caused by a mutation in PTPN11

2017 ◽  
Vol 97 ◽  
pp. 228-234 ◽  
Author(s):  
Josephine W.I. van Nierop ◽  
Dorothée C. van Trier ◽  
Ineke van der Burgt ◽  
Jos M.T. Draaisma ◽  
Emmanuel A.M. Mylanus ◽  
...  
Keyword(s):  
Clinical Features ◽  
Cochlear Implantation ◽  
Noonan Syndrome ◽  
Multiple Lentigines

scholarly journals Further Evidence for the Implication of LZTR1, a Gene not Associated with the Ras-Mapk Pathway, in the Pathogenesis of Noonan Syndrome

2017 ◽  
Vol 09 (06) ◽  
Author(s):  
Nehla Ghedira ◽  
Lilia Kraoua ◽  
Arnaud Lagarde ◽  
Rim Ben Abdelaziz ◽  
Sylviane Olschwang ◽  
...  
Keyword(s):  
Noonan Syndrome ◽  
Mapk Pathway

scholarly journals Impaired Binding of 14-3-3 to C-RAF in Noonan Syndrome Suggests New Approaches in Diseases with Increased Ras Signaling

2010 ◽  
Vol 30 (19) ◽  
pp. 4698-4711 ◽  
Author(s):  
Manuela Molzan ◽  
Benjamin Schumacher ◽  
Corinna Ottmann ◽  
Angela Baljuls ◽  
Lisa Polzien ◽  
...  
Keyword(s):  
Protein Interaction ◽  
Noonan Syndrome ◽  
Developmental Disorders ◽  
Mapk Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Ras Signaling ◽  
Membrane Recruitment ◽  
Protein Protein Interaction ◽  
Binding Data ◽  
Mitogen Activated Protein

ABSTRACT The Ras-RAF-mitogen-activated protein kinase (Ras-RAF-MAPK) pathway is overactive in many cancers and in some developmental disorders. In one of those disorders, namely, Noonan syndrome, nine activating C-RAF mutations cluster around Ser259, a regulatory site for inhibition by 14-3-3 proteins. We show that these mutations impair binding of 14-3-3 proteins to C-RAF and alter its subcellular localization by promoting Ras-mediated plasma membrane recruitment of C-RAF. By presenting biophysical binding data, the 14-3-3/C-RAFpS259 crystal structure, and cellular analyses, we indicate a mechanistic link between a well-described human developmental disorder and the impairment of a 14-3-3/target protein interaction. As a broader implication of these findings, modulating the C-RAFSer259/14-3-3 protein-protein interaction with a stabilizing small molecule may yield a novel potential approach for treatment of diseases resulting from an overactive Ras-RAF-MAPK pathway.

scholarly journals Etiology and Treatment of Growth Delay in Noonan Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Fernando Rodríguez ◽  
Ximena Gaete ◽  
Fernando Cassorla
Keyword(s):  
Growth Hormone ◽  
Noonan Syndrome ◽  
Mapk Pathway ◽  
Recombinant Human Growth Hormone ◽  
Growth Failure ◽  
Proper Function ◽  
Growth Delay ◽  
Childhood And Adolescence ◽  
Treatment Protocols ◽  
Somatotrophic Axis

Noonan syndrome is characterized by multiple phenotypic features, including growth retardation, which represents the main cause of consultation to the clinician. Longitudinal growth during childhood and adolescence depends on several factors, among them an intact somatotrophic axis, which is characterized by an adequate growth hormone (GH) secretion by the pituitary, subsequent binding to its receptor, proper function of the post-receptor signaling pathway for this hormone (JAK-STAT5b and RAS/MAPK), and ultimately by the production of its main effector, insulin like growth factor 1 (IGF-1). Several studies regarding the function of the somatotrophic axis in patients with Noonan syndrome and data from murine models, suggest that partial GH insensitivity at a post-receptor level, as well as possible derangements in the RAS/MAPK pathway, are the most likely causes for the growth failure in these patients. Treatment with recombinant human growth hormone (rhGH) has been used extensively to promote linear growth in these patients. Numerous treatment protocols have been employed so far, but the published studies are quite heterogeneous regarding patient selection, length of treatment, and dose of rhGH utilized, so the true benefit of GH therapy is somewhat difficult to establish. This review will discuss the possible etiologies for the growth delay, as well as the outcomes following rhGH treatment in patients with Noonan syndrome.

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