Congenital heart diseases in children with Noonan syndrome: An expanded cardiac spectrum with high prevalence of atrioventricular canal

Marino, Bruno; Digilio, María Cristina; Toscano, Alessandra; Giannotti, Aldo; Dallapiccola, Bruno

doi:10.1016/s0022-3476(99)70088-0

Cited by 221 publications

(170 citation statements)

References 43 publications

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“…Interestingly, one patient with MEK1 mutation had tetralogy of Fallot with abnormal pulmonary venous return. Tetralogy of Fallot is included among CHDs reported in clinical series of patients with NS, 24 although molecular studies have documented this CHD only in cases with RAF1 mutations. 10,11 To our knowledge, the association of tetralogy of Fallot and abnormal pulmonary venous return, which is suggestive of a partial expression of a cardiac laterality defect, has never been described in patients with mutations in the Ras/ MAPK pathway.…”

Section: Discussionmentioning

confidence: 99%

Spectrum of MEK1 and MEK2 gene mutations in cardio-facio-cutaneous syndrome and genotype–phenotype correlations

et al. 2009

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Cardio-facio-cutaneous syndrome (CFCS) is a rare disease characterized by mental retardation, facial dysmorphisms, ectodermal abnormalities, heart defects and developmental delay. CFCS is genetically heterogeneous and mutations in the KRAS, BRAF, MAP2K1 (MEK1) and MAP2K2 (MEK2) genes, encoding for components of the RAS-mitogen activated protein kinase (MAPK) signaling pathway, have been identified in up to 90% of cases. Here we screened a cohort of 33 individuals with CFCS for MEK1 and MEK2 gene mutations to further explore their molecular spectrum in this disorder, and to analyze genotypephenotype correlations. Three MEK1 and two MEK2 mutations were detected in six patients. Two missense MEK1 (L42F and Y130H) changes and one in-frame MEK2 (K63_E66del) deletion had not been reported earlier. All mutations were localized within exon 2 or 3. Together with the available records, the present data document that MEK1 mutations are relatively more frequent than those in MEK2, with exons 2 and 3 being mutational hot spots in both genes. Mutational analysis of the affected MEK1 and MEK2 exons did not reveal occurrence of mutations among 75 patients with Noonan syndrome, confirming the low prevalence of MEK gene defects in this disorder. Clinical review of known individuals with MEK1/MEK2 mutations suggests that these patients show dysmorphic features, ectodermal abnormalities and cognitive deficit similar to what was observed in BRAF-mutated patients and in the general CFCS population. Conversely, congenital heart defects, particularly mitral valve and septal defects, and ocular anomalies seem to be less frequent among MEK1/MEK2 mutation-positive patients.

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Section: Discussionmentioning

confidence: 99%

Spectrum of MEK1 and MEK2 gene mutations in cardio-facio-cutaneous syndrome and genotype–phenotype correlations

et al. 2009

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“…Atrial and/or ventricular septal defects are mentioned in 5-15% of cases [11,18,24]. Some more rare malformations are coarctation of the aorta and structural mitral valve abnormalities [1,12,18]. Patients with a PTPN11 gene mutation more often have pulmonary stenosis, and patients without a PTPN11 gene mutation more often have hypertrophic cardiomyopathy [10,26].…”

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confidence: 99%

Are ECG abnormalities in Noonan syndrome characteristic for the syndrome?

et al. 2008

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“…NCVM is mostly involved solely in left ventricle, right ventricular NCVM and biventricular NCVM occur infrequently. Hypertrophic cardiomyopathy (HCM) is one of the most frequently diagnosed cardiac conditions in NS whereas NCVM presents rarely (4) . For that reason, differentiating NCVM from HCM is crucial for treatment.…”

Section: Discussionmentioning

confidence: 99%

Management of Rare Combination of Cardiac Anomalies in A Patient with Noonan Syndrome

Alpat¹

2015

Kosuyolu Heart Journal

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Noonan syndrome is a rare disorder in which different cardiac abnormalities can exist. This report describes the combination of cardiac abnormalities in a patient with Noonan syndrome, which has not been reported previously. Coexisting cardiac abnormalities were: atrial septal defect, atrial fi brillation and noncompaction of the ventricular myocardium. Surgical fenestrated closure of atrial septal defect and concomitant maze procedure were performed. Surgery of congenital heart defects in syndromic patients has different diffi culties than those in nonsyndromic patients. Thus, specifi c approach should be taken in these patients.

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Congenital heart diseases in children with Noonan syndrome: An expanded cardiac spectrum with high prevalence of atrioventricular canal

Cited by 221 publications

References 43 publications

Spectrum of MEK1 and MEK2 gene mutations in cardio-facio-cutaneous syndrome and genotype–phenotype correlations

Spectrum of MEK1 and MEK2 gene mutations in cardio-facio-cutaneous syndrome and genotype–phenotype correlations

Are ECG abnormalities in Noonan syndrome characteristic for the syndrome?

Management of Rare Combination of Cardiac Anomalies in A Patient with Noonan Syndrome

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