Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
5.4
3.9
Journals
JCM
Special Issues
Noonan Syndrome: New Insights in Clinical and Genetic Features
share announcement

Noonan Syndrome: New Insights in Clinical and Genetic Features

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Endocrinology & Metabolism".

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 9563

Special Issue Editor

Prof. Dr. Cees Noordam

E-Mail Website
Guest Editor
1. Centre for Paediatric Endocrinology Zurich (PEZZ), Zurich, Switzerland
2. Department of Pediatrics, Radboud University Medical Centre, Nijmegen, The Netherlands
Interests: noonan syndrome; growth; growth hormone; genotype-phenotype relationships; prader willi syndrome; syndromes (in general)

Special Issue Information

Dear Colleagues, 

Noonan syndrome is a multisystem genetic disorder with an estimated incidence of 1 in 1000 to 1 in 2500 live births. Noonan syndrome is diagnosed clinically by the observation of key features: characteristic face, congenital heart defects, and short stature. Noonan syndrome is predominantly an autosomal-dominant condition, genetically and clinically heterogeneous, and the most common syndrome among RAS-o-pathies. RAS-o-pathies are a clinically defined group of syndromes caused by germline mutations in genes that encode components or regulators of the Ras/mitogen-activated protein kinase (MAPK) pathway. The RAS/MAPK pathway plays an essential role in regulating the cell cycle, cellular growth, differentiation, and senescence, all of which are critical to normal development.

Over the last decade, knowledge on clinical and genetic features and pathophysiologic backgrounds of Noonan syndrome has increased. This Special Issue on “Noonan Syndrome: New Insights in Clinical and Genetic Features” is focused on both clinical as well as basic and translational research in this field. In particular, original and up-to-date review articles are solicited regarding clinical and genetic aspects, disease models, and molecular mechanisms of Noonan syndrome. Moreover, studies on upcoming therapeutic approaches are also of interest.

Prof. Dr. Cees Noordam
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Noonan syndrome
  • clinical
  • genetic
  • therapy
  • RAS-o-pathy
  • translational
  • endocrine

Published Papers (4 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

15 pages, 334 KiB  
Article
Cognitive Phenotype and Psychopathology in Noonan Syndrome Spectrum Disorders through Various Ras/MAPK Pathway Associated Gene Variants
by Ellen Wingbermühle, Renée L. Roelofs, Wouter Oomens, Jennifer Kramer, Jos M. T. Draaisma, Erika Leenders, Tjitske Kleefstra, Roy P. C. Kessels and Jos I. M. Egger
J. Clin. Med. 2022, 11(16), 4735; https://doi.org/10.3390/jcm11164735 - 13 Aug 2022
Cited by 8 | Viewed by 2349
Abstract
Cognitive difficulties are argued to be common in patients with Noonan syndrome spectrum disorders (NSSDs), but findings are based on studies in which patients with variants in PTPN11 (prevalence ~50%) were overrepresented. The current study, using a structured clinical approach, describes the cognitive [...] Read more.
Cognitive difficulties are argued to be common in patients with Noonan syndrome spectrum disorders (NSSDs), but findings are based on studies in which patients with variants in PTPN11 (prevalence ~50%) were overrepresented. The current study, using a structured clinical approach, describes the cognitive phenotype and psychopathology of 100 patients (aged 6 to 61 years) with nine different gene variants in the Ras/MAPK pathway underlying NSSDs (PTPN11n = 61, PTPN11 Noonan syndrome with multiple lentigines n = 3, SOS1n = 14, KRASn = 7, LZTR1n = 5, RAF1n = 4, SHOC2n = 2, CBLn = 2, SOS2n = 2). After weighted assessment and bootstrapping of the results of individual neuropsychological assessments and measures of psychopathology, cognitive performances in most variant groups were within the ranges of expectation. IQs were significantly lower in patients with variants in PTPN11, KRAS, RAF1, and SHOC2, but no specific cognitive impairments were found. The performances of younger participants (<16 years of age) did not differ from those of adults. Alexithymia and internalizing problems were more frequent in patients with variants in PTPN11 and SOS1, while PTPN11 patients also showed higher levels of externalizing problems. These results stress the need to take intelligence into account when interpreting lower cognitive performances in individual neuropsychological assessments, which is crucial for an adequate understanding and guidance of patients with NSSDs. Full article
(This article belongs to the Special Issue Noonan Syndrome: New Insights in Clinical and Genetic Features)

Review

Jump to: Research

8 pages, 512 KiB  
Review
Lymphatic Phenotype of Noonan Syndrome: Innovative Diagnosis and Possible Implications for Therapy
by Lotte E. R. Kleimeier, Caroline van Schaik, Erika Leenders, Maxim Itkin, Willemijn M. Klein and Jos M. T. Draaisma
J. Clin. Med. 2022, 11(11), 3128; https://doi.org/10.3390/jcm11113128 - 31 May 2022
Cited by 5 | Viewed by 2007
Abstract
Dysregulation of the Ras/Mitogen-activated protein kinase (MAPK) signaling pathway is suggested to play a pivotal role in the development of the lymphatic system in patients with Noonan Syndrome (NS). Pathogenic gene variants in the Ras/MAPK pathway can therefore lead to various lymphatic diseases [...] Read more.
Dysregulation of the Ras/Mitogen-activated protein kinase (MAPK) signaling pathway is suggested to play a pivotal role in the development of the lymphatic system in patients with Noonan Syndrome (NS). Pathogenic gene variants in the Ras/MAPK pathway can therefore lead to various lymphatic diseases such as lymphedema, chylo-thorax and protein losing enteropathy. Diagnosis and treatment of the lymphatic phenotype in patients with NS remain difficult due to the variability of clinical presentation, severity and, probably, underlying unknown pathophysiologic mechanism. The objective of this article is to give an overview of the clinical presentation of lymphatic disease in relation to central conducting lymphatic anomalies (CCLA) in NS, including new diagnostic and therapeutic options. We visualized the central conducting lymphatic system using heavily T2-weighted MR imaging (T2 imaging) and Dynamic Contrast-enhanced MR Lymphangiography (DCMRL) and compared these results with the lymphatic clinical presentation in seven patients with NS. Our results show that most patients with NS and lymphatic disease have CCLA. Therefore, it is probable that CCLA is present in all patient with NS, presenting merely with lymphedema, or without sensing lymphatic symptoms at all. T2 imaging and DCMRL can be indicated when CCLA is suspected and this can help to adjust therapeutic interventions. Full article
(This article belongs to the Special Issue Noonan Syndrome: New Insights in Clinical and Genetic Features)
►▼ Show Figures

Figure 1

8 pages, 230 KiB  
Review
Growth, Endocrine Features, and Growth Hormone Treatment in Noonan Syndrome
by Jovanna Dahlgren and Cees Noordam
J. Clin. Med. 2022, 11(7), 2034; https://doi.org/10.3390/jcm11072034 - 5 Apr 2022
Cited by 9 | Viewed by 3138
Abstract
Noonan syndrome is a heterogeneous congenital disorder. The main features are typical facial features, short stature and cardiac defects. The diagnosis is clinical: in 80% of patients with Noonan syndrome a genetic defect can be shown. Inheritance is predominantly autosomal dominant and seldom [...] Read more.
Noonan syndrome is a heterogeneous congenital disorder. The main features are typical facial features, short stature and cardiac defects. The diagnosis is clinical: in 80% of patients with Noonan syndrome a genetic defect can be shown. Inheritance is predominantly autosomal dominant and seldom autosomal recessive. In 2001, PTPN11 was the first gene connected to Noonan syndrome, and until now, at least 20 other genes have been discovered. All genes code for proteins involved in the RAS-MAP-kinase pathway, and therefore, Noonan syndrome is one of the known RASopathies. Other RASopathies include neurofibromatosis and CFC syndrome. Short stature is one of the defining features of Noonan syndrome. The cause is not fully understood but is multifactorial. Other endocrinological features are confined to delayed puberty and hypogonadism in boys and males. To increase adult height, children with Noonan syndrome have been treated with human growth hormone since the 1990s. This seems to be beneficial in most of the children treated. In this narrative review, we describe the current knowledge on growth, endocrinological features and growth hormone treatment in patients with Noonan syndrome. Full article
(This article belongs to the Special Issue Noonan Syndrome: New Insights in Clinical and Genetic Features)
9 pages, 247 KiB  
Review
Feeding Problems in Patients with Noonan Syndrome: A Narrative Review
by Dagmar K. Tiemens, Leenke van Haaften, Erika Leenders, Annemiek M. J. van Wegberg, Bregtje Gunther Moor, Joyce Geelen and Jos M. T. Draaisma
J. Clin. Med. 2022, 11(3), 754; https://doi.org/10.3390/jcm11030754 - 30 Jan 2022
Cited by 6 | Viewed by 3577
Abstract
Noonan syndrome (NS) belongs to the group of Noonan syndrome spectrum disorders (NSSD), which is a group of phenotypically related conditions. Feeding problems are often present not only in infancy but also in childhood, and even beyond that period. We describe the different [...] Read more.
Noonan syndrome (NS) belongs to the group of Noonan syndrome spectrum disorders (NSSD), which is a group of phenotypically related conditions. Feeding problems are often present not only in infancy but also in childhood, and even beyond that period. We describe the different aspects of feeding problems using a (theoretical) concept proposed in 2019. More than 50% of infants with NS develop feeding problems, and up to half of these infants will be tube-dependent for some time. Although, in general, there is a major improvement between the age of 1 and 2 years, with only a minority still having feeding problems after the age of 2 years, as long as the feeding problems continue, the impact on the quality of life of both NS infants and their caregivers may be significant. Feeding problems in general improve faster in children with a pathogenic PTPN11 or SOS1 variant. The mechanism of the feeding problems is complex, and may be due to medical causes (gastroesophageal reflux disease and delayed gastric emptying, cardiac disease and infections), feeding-skill dysfunction, nutritional dysfunction with increased energy demand, or primary or secondary psychosocial dysfunction. Many of the underlying mechanisms are still unknown. The treatment of the feeding problems may be a medical challenge, especially when the feeding problems are accompanied by feeding-skill dysfunction and psychosocial dysfunction. This warrants a multidisciplinary intervention including psychology, nutrition, medicine, speech language pathology and occupational therapy. Full article
(This article belongs to the Special Issue Noonan Syndrome: New Insights in Clinical and Genetic Features)
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-4
Back to TopTop