Noonan syndrome and clinically related disorders
Marco Tartaglia1, Bruce D Gelb, Martin Zenker
1Dipartimento di Ematologia, Oncologia e Medicina Molecolare, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome, Italy. mtartaglia@iss.it
Summary
Noonan syndrome is a common developmental disorder with varied symptoms. Genetic mutations in RAS-MAPK pathway genes explain 75% of cases, aiding molecular diagnosis.
Area of Science:
- Genetics
- Developmental Biology
- Clinical Medicine
Background:
- Noonan syndrome is a frequent, heterogeneous developmental disorder.
- Key features include growth retardation, facial dysmorphism, heart defects, and developmental delays.
- It follows autosomal dominant inheritance.
Purpose of the Study:
- To review the clinical features of Noonan syndrome and related disorders.
- To discuss the molecular mechanisms of pathogenesis.
- To outline genotype-phenotype correlations.
Main Methods:
- Literature review of clinical and genetic studies.
- Analysis of documented mutations in nine genes.
- Overview of the RAS-mitogen-activated protein kinases (MAPK) pathway.
Main Results:
- Heterozygous mutations in PTPN11, SOS1, KRAS, NRAS, RAF1, BRAF, SHOC2, MEK1, and CBL genes are implicated.
- Molecular diagnosis is possible in approximately 75% of individuals.
- Affected genes are part of the RAS-MAPK signaling pathway.
Conclusions:
- Understanding the genetic basis of Noonan syndrome facilitates molecular diagnosis.
- The RAS-MAPK pathway is central to the pathogenesis of Noonan syndrome.
- Genotype-phenotype correlations are crucial for clinical management.
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