Cardiovascular malformations in Turner's and Noonan's syndrome.

Hauwaert, L G Van der; Fryns, J P; Dumoulin, M; Logghe, N.

doi:10.1136/hrt.40.5.500

Cited by 59 publications

(21 citation statements)

References 22 publications

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“…7,8 In recent years, however, investigations in asymptomatic individuals have revealed a far more complex and extensive cardiovascular phenotype. Magnetic resonance imaging has revealed that most women with TS have abnormal cardiovascular anatomy.…”

Section: Clinical Perspective P 1670mentioning

confidence: 99%

Aortic Dilatation and Dissection in Turner Syndrome

et al. 2007

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Background-The risk for aortic dissection is increased among relatively young women with Turner syndrome (TS). It is unknown whether aortic dilatation precedes acute aortic dissection in TS and, if so, what specific diameter predicts impending deterioration. Methods and Results-Study subjects included 166 adult volunteers with TS (average age, 36.2 years) who were not selected for cardiovascular disease and 26 healthy female control subjects. Ascending and descending aortic diameters were measured by magnetic resonance imaging at the right pulmonary artery. TS women were on average 20 cm shorter, yet average aortic diameters were identical in the 2 groups. Ascending aortic diameters normalized to body surface area (aortic size index) were significantly greater in TS, and Ϸ32% of TS women had values greater than the 95th percentile of 2.0 cm/m 2 . Ascending diameter/descending diameter ratios also were significantly greater in the TS group. During Ϸ3 years of follow-up, aortic dissections occurred in 3 women with TS, for an annualized rate of 618 cases/100 000 woman-years. These 3 subjects had ascending aortic diameters of 3.7 to 4.8 cm and aortic size indices Ͼ2.5 cm/m 2 . Conclusions-The risk for aortic dissection is greatly increased in young women with TS. Because of their small stature, ascending aortic diameters of Ͻ5 cm may represent significant dilatation; thus, the use of aortic size index is preferred. Individuals with a dilated ascending aorta defined as aortic size index Ͼ2.0 cm/m 2 require close cardiovascular surveillance. Those with aortic size index Ն2.5 cm/m 2 are at highest risk for aortic dissection.

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Section: Clinical Perspective P 1670mentioning

confidence: 99%

Aortic Dilatation and Dissection in Turner Syndrome

et al. 2007

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“…Turner syndrome is associated with congenital malformations such as coarctation of the aorta, horse shoe kidney and pterygium colli (304,305), as well as less severe congenital malformations of the heart (306,307), especially with the 45,X karyotype ( Fig. 6) (307)(308)(309)(310).…”

Section: Congenital Malformations Of the Heartmentioning

confidence: 99%

Epidemiological, endocrine and metabolic features in Turner syndrome

2004

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Turner syndrome is one of the more common genetic disorders, associated with abnormalities of the X chromosome, and occurring in about 50 per 100 000 liveborn girls. Turner syndrome is usually associated with reduced adult height, gonadal dysgenesis and thus insufficient circulating levels of female sex steroids, and infertility. A number of other signs and symptoms are seen more frequently with the syndrome. Morbidity and mortality are increased. The average intellectual performance is within the normal range. A number of recent studies have provided new insights with respect to epidemiology, cardiology, endocrinology and metabolism. Treatment with GH during childhood and adolescence allows a considerable gain in adult height, although verylong-term consequences of this treatment are not clear. Puberty has to be induced in most cases, and female sex hormone replacement therapy is given during the adult years. The proper dose of hormone replacement therapy (HRT) has not been established, and, likewise, benefits and/or drawbacks from HRT have not been thoroughly evaluated. Since the risk of cardiovascular and endocrinological disease is clearly elevated, proper care during adulthood is emphasized. In summary, Turner syndrome is a condition associated with a number of diseases and conditions which are reviewed in the present paper.

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“…In the majority of cases, NS follows autosomal dominant inheritance and is characterized by short stature, facial dysmorphia, skeletal anomalies, and congenital heart disease (4)(5)(6). Among the heart defects, pulmonary valve stenosis and hypertrophic cardiomyopathy are most prominent (6,7). Understanding the exact cellular mechanism(s) by which dysfunction of Shp2 causes valve malformations may provide the basis for future development of novel therapeutic approaches.…”

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confidence: 99%

Role of ERK1/2 signaling in congenital valve malformations in Noonan syndrome

Krenz

Gulick

Osińska

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Noonan syndrome (NS) is the most common nonchromosomal genetic disorder associated with cardiovascular malformations. The most prominent cardiac defects in NS are pulmonary valve stenosis and hypertrophic cardiomyopathy. Gain-of-function mutations in the protein tyrosine phosphatase Shp2 have been identified in 50% of NS families. We created a NS mouse model with selective overexpression of mutant Shp2 (Q79R-Shp2) in the developing endocardial cushions. In our model, Cre recombinase driven by the Tie2 promoter irreversibly activates transgenic Q79R-Shp2 expression in the endothelial-derived cell lineage. Q79R-Shp2 expression resulted in embryonic lethality by embryonic day 14.5. Importantly, mutant embryos showed significantly enlarged endocardial cushions in the atrioventricular canal and in the outflow tract. In contrast, overexpression of wild-type Shp2 protein at comparable levels did not enhance endocardial cushion growth or alter the morphology of the mature adult valves. Expression of Q79R-Shp2 was accompanied by increased ERK1/2 activation in a subset of cells within the cushion mesenchyme, suggesting that hyperactivation of this signaling pathway may play a pathogenic role. To test this hypothesis in vivo, Q79R-Shp2-expressing mice were crossed with mice carrying either a homozygous ERK1 or a heterozygous ERK2 deletion. Deletion of ERK1 completely rescued the endocardial cushion phenotype, whereas ERK2 protein reduction did not affect endocardial cushion size. Constitutive hyperactivation of ERK1/2 signaling alone with a transgenic approach resulted in a phenocopy of the valvular phenotype. The data demonstrate both necessity and sufficiency of increased ERK activation downstream of Shp2 in mediating abnormal valve development in a NS mouse model.

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Cardiovascular malformations in Turner's and Noonan's syndrome.

Cited by 59 publications

References 22 publications

Aortic Dilatation and Dissection in Turner Syndrome

Aortic Dilatation and Dissection in Turner Syndrome

Epidemiological, endocrine and metabolic features in Turner syndrome

Role of ERK1/2 signaling in congenital valve malformations in Noonan syndrome

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