Noonan syndrome

Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Canada.
American Journal of Medical Genetics Part C Seminars in Medical Genetics (Impact Factor: 3.91). 08/2007; 145C(3):274-9. DOI: 10.1002/ajmg.c.30138
Source: PubMed


Noonan syndrome is a common autosomal dominant condition caused by multiple genes in the RasMAPK pathway. The adult phenotype can be extremely subtle, and many adults are diagnosed only after the birth of a more obviously affected child. Whether diagnosis is made in childhood or adulthood, initial and ongoing evaluation of many systems can have considerable health benefits.

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    • "Noonan syndrome (NS, OMIM 163950) is a common genetic disorder characterized by congenital heart disease, short stature, thoracic abnormality, cryptorchidism, mental retardation, and a typical facial appearance, among other characteristics [1,2]. NS is transmitted as an autosomal dominant trait, and is genetically heterogeneous. "
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    ABSTRACT: Noonan syndrome is an autosomal, dominantly inherited disease; it is physically characterized by short stature, short neck, webbed neck, abnormal auricles, high arched palate, and cardiovascular malformation. Its pathological condition is thought to be due to a gain-of-function mutation in the Ras-mitogen-activated protein kinase (MAPK) signal transduction pathway. Eyelid abnormalities such as ocular hypertelorism and blepharoptosis are the most commonly observed eye complications. We report a case of Noonan syndrome associated with mature cataract that required operation. A 42-year-old man was diagnosed with Noonan syndrome at the age of 1 year. He underwent an eye examination after complaining of decreased visual acuity in the right eye and was diagnosed with mature cataract, which was treated by cataract surgery. There were no intraoperative complications, and the postoperative course was uneventful. Protein analysis of lens capsule and epithelium at capsulorhexis showed MAPK cascade proteins such as ERK and p38MAPK were upregulated. An abnormality in the PTPN11 gene was also observed; a potential mechanism of cataract onset may be that opacity of the lens rapidly progressed due to abnormal activation of the Ras-MAPK signal transduction pathway. This case highlights the possible association of cataract formation with MAPK cascade protein upregulation in Noonan syndrome.
    BMC Ophthalmology 11/2013; 13(1):70. DOI:10.1186/1471-2415-13-70 · 1.02 Impact Factor
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    • "In some of these disorders, a further level of complexity is due to genetic heterogeneity, which explains, in part, the observed clinical variability. Noonan syndrome (NS, OMIM 163950), which is the most common among these diseases, occurring approximately in 1:1000–1:2500 live births, represents a paradigmatic condition [Allanson, 2007; Tartaglia et al., 2010; Van der Burgt, 2007]. NS is genetically heterogeneous, with activating mutations in PTPN11, SOS1, KRAS, NRAS, RAF1, and BRAF occurring in approximately 75% of affected individuals [Tartaglia et al., 2011]. "
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    ABSTRACT: Noonan syndrome (NS) is among the most common nonchromosomal disorders affecting development and growth. NS is genetically heterogeneous, being caused by germline mutations affecting various genes implicated in the RAS signaling network. This network transduces extracellular signals into intracellular biochemical and transcriptional responses controlling cell proliferation, differentiation, metabolism, and senescence. To explore the transcriptional consequences of NS-causing mutations, we performed global mRNA expression profiling on peripheral blood mononuclear cells obtained from 23 NS patients carrying heterozygous mutations in PTPN11 or SOS1. Gene expression profiling was also resolved in five subjects with Noonan-like syndrome with loose anagen hair (NS/LAH), a condition clinically related to NS and caused by an invariant mutation in SHOC2. Robust transcriptional signatures were found to specifically discriminate each of the three mutation groups from 21 age- and sex-matched controls. Despite the only partial overlap in terms of gene composition, the three signatures showed a notable concordance in terms of biological processes and regulatory circuits affected. These data establish expression profiling of peripheral blood mononuclear cells as a powerful tool to appreciate differential perturbations driven by germline mutations of transducers involved in RAS signaling and to dissect molecular mechanisms underlying NS and other RASopathies.
    Human Mutation 04/2012; 33(4):703-9. DOI:10.1002/humu.22026 · 5.14 Impact Factor
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    ABSTRACT: Cardiovascular abnormalities, especially structural congenital heart defects, commonly occur in malformation syndromes and genetic disorders. Individuals with syndromes comprise a significant proportion of those affected with selected congenital heart defects such as complete atrioventricular canal, interrupted arch type B, supravalvar aortic stenosis, and pulmonary stenosis. As these individuals age, they contribute to the growing population of adults with special health care needs. Although most will require longterm cardiology follow-up, primary care providers, geneticists, and other specialists should be aware of (1) the type and frequency of cardiovascular abnormalities, (2) the range of clinical outcomes, and (3) guidelines for prospective management and treatment of potential complications. This article reviews fundamental genetic, cardiac, medical, and reproductive issues associated with common genetic syndromes that are frequently associated with a cardiovascular abnormality. New data are also provided about the cardiac status of adults with a 22q11.2 deletion and with Down syndrome.
    Genetics in medicine: official journal of the American College of Medical Genetics 08/2008; 10(7):469-94. DOI:10.1097/GIM.0b013e3181772111 · 7.33 Impact Factor
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