Prolonged rate-corrected QT interval and other electrocardiogram abnormalities in girls with Turner syndrome.

BACKGROUND: We recently reported that electrocardiographic abnormalities are common in adults with monosomy X (Turner syndrome), but this issue has not been investigated in girls with Turner syndrome. PATIENTS AND METHODS: We analyzed electrocardiograms in 78 girls with Turner syndrome and 50 age-matched control girls. The girls with Turner syndrome had additional cardiac and metabolic evaluations. RESULTS: Girls with Turner syndrome were more likely to demonstrate > or = 1 electrocardiographic findings including right axis deviation, right ventricular hypertrophy, accelerated atrioventricular conduction, T-wave abnormalities, and a prolonged rate-corrected QT interval. The right-sided findings were associated with partial anomalous pulmonary venous connection, but the etiology of the other findings remains unknown. The rate-corrected QT interval was significantly longer in girls with Turner syndrome (431 +/- 22 vs 407 +/- 21 milliseconds). Twenty-eight girls with Turner syndrome but only 2 controls had a rate-corrected QT interval above the reference range. We found no correlation between body habitus, cardiac dimensions, or metabolic parameters and the rate-corrected QT interval duration in girls with Turner syndrome. CONCLUSIONS: Cardiac conduction and repolarization abnormalities seem to affect both young girls and adults with Turner syndrome equally, suggesting that electrophysiologic defects are intrinsic to the syndrome and indicating that electrocardiogram analysis should be included in evaluating and monitoring even the youngest patients with Turner syndrome. Attention to the rate-corrected QT interval is important, because some common medications may further prolong this interval and increase the risk of arrhythmias.

Monosomy for the X-chromosome is associated with an atherogenic lipid profile.

CONTEXT AND OBJECTIVE: Men typically have a more atherogenic lipid profile than women characterized by higher low-density lipoprotein (LDL) cholesterol and triglyceride levels and reduced lipid particle size, contributing to a greater risk for coronary disease. To determine whether X-chromosomal gene dosage affects lipid metabolism independent of sex steroid effects, we compared lipid profiles in age- and body mass-matched young women with ovarian failure, differing only in X-chromosome dosage. DESIGN, SETTING, AND PATIENTS: Women with premature ovarian failure associated with monosomy X or Turner syndrome (TS, n = 118) were compared with women with 46,XX premature ovarian failure (n = 51) in an in-patient clinical research center unit at the National Institutes of Health. These women were normally on estrogen replacement treatment but discontinued the estrogen 2 wk before study. MAJOR OUTCOMES: Fasting lipid levels and nuclear magnetic resonance lipid particle profiles in the two study groups were the major outcomes. RESULTS: Average age and body mass were similar in the two groups of women, but LDL cholesterol (P = 0.001) and triglyceride levels (P = 0.0005) were higher in the TS group. Also among women with TS, average LDL particle size was reduced (P < 0.0001) and LDL particle concentration increased, with a 2-fold increase in the smallest particle categories (P < 0.0001). Whereas total high-density lipoprotein cholesterol levels were similar, high-density lipoprotein particle size was significantly smaller in women with TS, compared with women with premature ovarian failure (P < 0.0001). CONCLUSIONS: Women with 45,X with ovarian failure exhibit a distinctly more atherogenic lipid profile than 46,XX women with ovarian failure, suggesting that the second X-chromosome contributes to a more salutary lipid profile in normal women, independent of sex steroid effects.

Prolongation of the cardiac QTc interval in Turner syndrome.

Anatomic anomalies of the cardiovascular system occur in approximately 50% of individuals with Turner syndrome (TS), with the specific genetic cause(s) for the heart defects still unknown. Because congenital heart disease may be associated with conduction system abnormalities, we compared electrocardiograms (ECGs) in 100 women with TS and 100 age-matched female controls. Women with TS were significantly more likely to demonstrate left posterior fascicular block (p < 0.005), accelerated AV conduction (p < 0.006), and T wave abnormalities (p < 0.006). The PR interval was significantly shorter (137 +/- 17 vs. 158 +/- 18 ms, p < 0.0001) and the rate-corrected QT interval (QTc) significantly longer in women with TS than in controls (423 +/- 19 ms vs. 397 +/- 18 ms; p < 0.0001). Twenty-one women with TS but no controls had a QTc greater than 440 ms. We found no statistically significant relation between body habitus, cardiac dimensions, evidence of congenital heart disease, or metabolic parameters and the incidence of ECG abnormalities or QTc duration in TS. Cardiac conduction and repolarization abnormalities appear to be intrinsic features of TS, suggesting that deletion of the second sex chromosome has more profound effects on the cardiovascular system than previously recognized, and that ECG analysis should be included in evaluating and monitoring patients with Turner syndrome.

Growth hormone treatment and aortic dimensions in Turner syndrome.

BACKGROUND: In recent years many girls with Turner syndrome (TS) have been treated with supraphysiological doses of GH to increase adult height. In addition to promoting statural growth, GH may have direct effects on the cardiovascular system. OBJECTIVE: We sought to determine whether GH treatment affects aortic diameter in girls with TS because there is an increased risk for aortic dilation and dissection in this syndrome. METHODS: In a retrospective, cross-sectional study, we compared ascending and descending aortic diameters measured by magnetic resonance imaging in GH-treated (n = 53) vs. untreated (n = 48) patients with TS participating in a National Institutes of Health protocol between 2001 and 2004. RESULTS: The average duration of GH treatment was 4.7 with se 0.4 yr (range 2-11 yr). The two groups were similar in age and weight, but GH-treated subjects were on average 8 cm taller (P = 0.002). The diameter of the ascending aorta was increased by 7.3% and descending aorta by 8.9% in the GH-treated group. However, after correction for age, height, weight, and presence of bicuspid aortic valve and coarctation, using a multiple regression, neither history of GH treatment nor the length of GH treatment had an effect on the aortic diameter. Weight (P = 0.02), height (P = 0.001), and presence of bicuspid aortic valve (P = 0.0001) were associated with larger ascending aortic diameter, whereas age (P = 0.008), height (P = 0.02), and history of coarctation (P = 0.006) were associated with larger descending aortic diameter. CONCLUSIONS: GH treatment of girls with TS does not seem to affect ascending or descending aortic diameter above the increase related to the larger body size.

Association between fetal lymphedema and congenital cardiovascular defects in Turner syndrome.

OBJECTIVES: Turner syndrome (TS) is associated with congenital cardiovascular defects (CCVDs), most commonly bicuspid aortic valve (BAV) and aortic coarctation (COARC), congenital renal anomalies, and fetal lymphedema. It has been theorized that compressive or obstructive effects of fetal lymphedema may actually cause cardiovascular and renal dysmorphogenesis in TS. The objective of this study was to determine whether there is a specific association between a history of fetal lymphedema and CCVDs in monosomy X, or TS, independent of karyotype or general severity of the phenotype. METHODS: This was a prospective study of 134 girls and women who have TS (mean age: 30 years) and were clinically evaluated for evidence of fetal lymphedema, classified as central (signified by the presence of neck webbing) or peripheral (current or perinatal, or dysplastic fingernails). The presence of BAV and/or COARC was detected by magnetic resonance imaging combined with echocardiography, and renal anomalies were determined by ultrasound. RESULTS: There is a strong association between developmental central lymphedema, signified by neck webbing, and the presence of BAV (chi2 = 10) and COARC (chi2 = 8). The association between webbed neck and CCVDs was independent of karyotype. There was, in contrast, no significant association between renal anomalies and webbed neck or CCVDs. CONCLUSIONS: The strong, statistically significant association between neck webbing and the presence of BAV and COARC in TS suggests a pathogenetic connection between fetal lymphatic obstruction and defective aortic development. The presence of neck webbing in TS should alert the clinician to the possibility of congenital cardiovascular defects.

Growth hormone therapy and bone mineral density in Turner syndrome.

In a previous report, preliminary data showed a significant reduction in cortical bone mineral density (BMD) in women with Turner syndrome that had been treated with GH compared with women with Turner syndrome that had not been treated. To clarify this point, we have investigated the effects of GH treatment at multiple sites in this case-control, cross-sectional study. There were 23 women per group, who were similar in age, height, body mass index, estrogen use, and ethnic makeup. Median age (range) at start and duration of GH treatment was 9 (3-17) and 5 (2-9) yr, respectively. GH-treated women had a slightly greater ( approximately 8%, P = 0.03) width of the radial shaft, but otherwise there were no significant differences between groups in bone dimensions or BMD at the distal radius, lumbar spine, or femoral neck. Furthermore, regression analysis in a linear model including independent variables of age, age at diagnosis, body mass index, presence of spontaneous puberty, and GH use confirmed that GH use did not contribute to variation in BMD.

Major vascular anomalies in Turner syndrome: prevalence and magnetic resonance angiographic features.

BACKGROUND: Turner syndrome (TS) is associated with aortic coarctation and dissection; hence, echocardiographic evaluation of all patients is currently recommended. X-ray angiography in clinically symptomatic patients has suggested a range of other vascular anomalies, but the true prevalence of such lesions in TS is unknown. To better understand the prevalence and pathogenesis of cardiovascular defects in TS, we prospectively evaluated a group of asymptomatic adult volunteers with TS using magnetic resonance (MR) angiography. METHODS AND RESULTS: A total of 85 adults with TS and 27 normal female adult volunteers underwent gadolinium-enhanced 3D MR angiography. A high prevalence of aortic anomalies was seen in women with TS, including elongation of the transverse arch (49%), aortic coarctation (12%), and aberrant right subclavian artery (8%). Venous anomalies were also prominent, including persistent left superior vena cava (13%) and partial anomalous pulmonary venous return (13%). None of these anomalies were found in healthy female controls. The constellation of elongation of the transverse arch, aortic coarctation, and persistent left superior vena cava was significantly associated with women with TS. Neck webbing and increased thoracic anterior-to-posterior dimension diameters were strong predictors for arterial and venous anomalies. CONCLUSIONS: Thoracic vascular anomalies are common in TS, occurring in approximately 50% of a group not preselected for cardiovascular disease. The highly significant association between neck webbing, increased chest diameter, and these vascular anomalies suggests that in utero, centrally localized lymphatic obstruction may contribute to these cardiovascular deformities in TS. Improved recognition of these often-undetected vascular lesions may be important for identification of patients in need of closer cardiovascular monitoring.