Noonan Syndrome: Clinical Features, Diagnosis, and Management Guidelines

@article{Romano2010NoonanSC,
  title={Noonan Syndrome: Clinical Features, Diagnosis, and Management Guidelines},
  author={Alicia A. Romano and Judith Allanson and Jovanna Dahlgren and Bruce D. Gelb and Bryan Hall and Mary Ella Pierpont and Amy E. Roberts and Wanda Robinson and Clifford M Takemoto and Jacqueline A. Noonan},
  journal={Pediatrics},
  year={2010},
  volume={126},
  pages={746 - 759}
}
Noonan syndrome (NS) is a common, clinically and genetically heterogeneous condition characterized by distinctive facial features, short stature, chest deformity, congenital heart disease, and other comorbidities. Gene mutations identified in individuals with the NS phenotype are involved in the Ras/MAPK (mitogen-activated protein kinase) signal transduction pathway and currently explain ∼61% of NS cases. Thus, NS frequently remains a clinical diagnosis. Because of the variability in… 

Figures and Tables from this paper

[Noonan syndrome: genetic and clinical update and treatment options].
Noonan syndrome – a new survey
TLDR
Noonan syndrome diagnosis is primarily based on clinical features, but molecular testing should be performed to confirm it in patients, and next-generation sequencing is the best choice for diagnostic testing.
Noonan Syndrome: Obstacles in Making a Diagnosis
TLDR
A late diagnosis of NS is described in a 14 year old male who presented with a normal height, but a predicted adult height discordant with his genetic potential, which highlights the obstacles that resulted in a delay in diagnosis and provides additional considerations for providers who have a clinical suspicion for NS.
Noonan syndrome.
TLDR
Most patients with Noonan syndrome are intellectually normal as adults, but some may require multidisciplinary evaluation and regular follow-up care.
Noonan syndrome: improving recognition and diagnosis.
TLDR
It is proposed that increasing awareness of NS among non-specialist HCPs and other professionals could help direct a parent/carer to seek specialist advice and increase the number of NS diagnoses, with the potential to optimise lifelong patient outcomes.
An atypical case of Noonan syndrome with KRAS mutation diagnosed by targeted exome sequencing
TLDR
With TES analysis, a pathogenic variant of c.458A > T in KRAS was detected in this patient with atypical NS phenotype and provided appropriate clinical management and genetic counseling.
Noonan syndrome
  • A. Turner
  • Medicine
    Journal of paediatrics and child health
  • 2014
TLDR
Increased awareness by paediatricians will lead to earlier diagnosis, and provide patients and their families with accurate genetic counselling, including options when planning pregnancy, and has become increasingly important in guiding management.
Novel insights in Noonan syndrome
TLDR
Clinical features and current treatment guidelines of Noonan Syndrome are reviewed in order to allow general paediatricians to better care children and adolescents with Noonan syndrome and to ensure a proper multidisciplinary approach.
...
...

References

SHOWING 1-10 OF 158 REFERENCES
Genotypic and phenotypic characterization of Noonan syndrome: New data and review of the literature
TLDR
Findings indicate that individuals with NS with specific mutations in PTPN11 are at risk of developing JMML, and the distribution of these mutations is reported on.
Lymphedema in Noonan syndrome: clues to pathogenesis and prenatal diagnosis and review of the literature.
TLDR
The major source of lymphedema in NS appears to be a presently undefined dysplasia of lymphatic vessels of unknown cause, which may provide an understanding of its role in shaping the NS phenotype.
Noonan's Syndrome and Autoimmune Diseases
TLDR
The aim of the present investigation was to study the prevalence of markers of autoimmune diseases, such as thyroglobulin antibodies (Tg-Ab) and antibodies to thyroid peroxidase (TPO-Ab), as well as IgA-antiendomysium antibodies (EMA) and IgA -antigliadin antibodies (AGA) in children with NS.
Clinical and molecular characterization of 40 patients with Noonan syndrome.
Noonan syndrome: the changing phenotype.
TLDR
This study has studied serial and family photographs of NS individuals in order to assess the likelihood of gene carriers' being missed in genetic studies and confirmed wide clinical variability within families, and suggests that the change of phenotype with age may have been falsely perceived as clinical heterogeneity.
Genetics and Variation in Phenotype in Noonan Syndrome
TLDR
Mutation analysis of the PTPN11 gene was carried out in Nijmegen in 150 patients with Noonan syndrome, with the most common mutation being A922G in exon 8 and a mutation that encoded the C-SH2 domain of thePTPN 11 gene in two unique patients who shared some uncommon features.
Multiple giant cell lesions in patients with Noonan syndrome and cardio-facio-cutaneous syndrome
TLDR
It is demonstrated that MGCL may occur in NS and CFCS with various underlying genetic alterations and no obvious genotype–phenotype correlation, which suggests that dysregulation of the RAS-MAPK pathway represents the common and basic molecular event predisposing to giant cell lesion formation in patients with NS andCFCS rather than specific mutation effects.
Noonan‐like syndrome mutations in PTPN11 in patients diagnosed with cherubism
To the Editor: Noonan-like/multiple giant-cell lesion syndrome (NLS; MIM 163955) is a rare autosomal dominant condition (1), which is characterized by facial dysmorphisms, developmental delay, short
Germline BRAF mutations in Noonan, LEOPARD, and cardiofaciocutaneous syndromes: Molecular diversity and associated phenotypic spectrum
TLDR
To investigate the phenotypic spectrum and molecular diversity of germline mutations affecting BRAF, subjects with a diagnosis of NS, LS, and CFCS were screened for the entire coding sequence of the gene.
...
...