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Background: Women with X-chromosome monosomy or Turner syndrome (TS) are at increased risk for aortic dilation and dissection. To better understand the pathology and develop tools to monitor the risk of aortic disease, we investigated N-terminal pro-brain natriuretic peptide (BNP) (NT-proBNP) levels in women with TS and healthy female controls. Methods: We evaluated NT-proBNP levels in women with karyotype-proven TS and healthy female volunteers in relation to ascending aortic diameter and descending aortic diameter measured by cardiovascular magnetic resonance imaging. Results: The NT-proBNP levels were strongly and positively correlated with ascending aortic diameter and descending aortic diameter in both cohorts. The TS group (n = 114, age 37.4 ± 12 yr) had greater body surface area–indexed aortic diameters and higher NT-proBNP levels than the control group (n = 27, age 46.4 ± 11 years): 88.3 ± 62.7 versus 53.5 ± 35 pg/mL, P = .0003. Within the TS group, NT-proBNP levels were higher in those with dilated ascending aorta (n = 42, 112.4 ± 75.7 pg/mL) compared with those with normal aortic dimensions (n = 72, 74.2 ± 49 pg/mL, P = .0014). Abnormally high NT-pro BNP levels were seen in 3 of 4 TS women who presented with previously undetected aortic aneurysm and/or dissection. Conclusions: The NT-proBNP levels are positively associated with aortic diameters in women with and without TS, suggesting a role for BNP in arterial wall homeostasis. Further study is necessary to determine whether NT-proBNP measurement may be used to monitor aortic diameter and/or detect aortic pathology in individuals at risk for aortic disease. [ABSTRACT FROM AUTHOR]

Objective: To evaluate uterine development of women with Turner syndrome (TS) receiving conventional medical care.Study Design: In a cross-sectional study we used ultrasonography for uterine evaluation in 86 women with TS 18 to 45 years of age participating in an intramural NIH study, and who had abnormal karyotypes in >70% of white blood cells. Outcomes were uterine dimensions and shape. Information on hormone treatment was obtained by personal interview.Results: Twenty-five percent had a mature in size and shape uterus, and 31% had an immature uterus, with the remainder in a transitional category. Twenty percent of all participants were not taking hormone replacement therapy (HRT) in the preceding year. The majority on treatment were taking conjugated estrogens (CE) or oral contraceptives (OC). Factors associated with uterine maturity were history of spontaneous puberty and duration and type of HRT, with estradiol-based treatment being the most effective. The age at starting HRT was not a critical factor.Conclusions: Women with TS may develop a normal uterus even at a late start of HRT given adequate duration of treatment and regardless of karyotype. [ABSTRACT FROM AUTHOR]

Objective: To determine whether cardiac dimensions were different in girls with Turner syndrome (TS) who received growth hormone (GH) compared with those who did not receive GH. Study design: This retrospective, cross-sectional study analyzed echocardiograms in 86 females with TS divided into GH-treated (n = 67) and untreated (n = 19) groups. The subjects all participated in the National Institutes of Health protocol between 2001 and 2006. Results: The average age was 16.2 years (range, 10 to 25 years), and average duration of GH treatment was 4.4 years (range, 1 to 14 years). The GH-treated group was taller by ∼7 cm (P = .004), but cardiac dimensions normalized to body surface area (BSA), including septal and posterior wall thickness and left ventricular (LV) mass and internal diameters, did not differ significantly between the 2 groups. The fractional shortening index was similar in the 2 groups. Multiple regression analyses indicated that BSA, but not duration of GH treatment, predicted LV dimensions in girls with TS. Conclusions: GH treatment of girls with TS increases stature but does not disproportionately affect cardiac dimensions. [Copyright &y& Elsevier]

Abstract: The advent of prenatal diagnosis in Turner Syndrome (TS) has brought with it challenges. Diagnosis may be prompted by characteristic abnormalities on prenatal ultrasound such as congenital heart disease and hydrops. Alternatively, diagnosis may be made incidentally on amniocentesis or chorionic villus sampling due to advanced maternal age. In cases of prenatal counseling, it is essential that counseling is provided by physicians and genetic counselors who are well-informed regarding TS and are aware of the current resources available. This chapter serves as a review of recent scientific literature regarding prenatal diagnosis in Turner Syndrome. [Copyright &y& Elsevier]

Abstract: Haploinsufficiency for the X-chromosome in females has important and multifaceted effects upon the cardiovascular system. Girls with Turner syndrome (TS) may demonstrate anatomic malformations affecting the heart, aorta and other major vessels, hypertension and abnormalities of heart rate, cardiac conduction and repolarization. The aorta is dilated in almost 50% of patients and aortic deterioration with aneurysm, dissection and rupture occurs with increased frequency in young and middle-aged patients. Finally many women with TS experience premature onset of coronary artery disease. This chapter reviews the more recent scientific literature regarding these abnormalities. [Copyright &y& Elsevier]

Abstract: The selective silencing of certain alleles depending on the parent of origin is known as genomic imprinting. Specific cognitive skills, statural growth and visceral adiposity have all been linked to the parental origin of the single normal X-chromosome in girls and women with Turner syndrome (TS). The putatively imprinted traits in TS reflect typical differences between eukaryotic males and females. This chapter reviews the evidence for parental X-chromosome imprinting in the TS phenotype. [Copyright &y& Elsevier]

Abstract: This review highlights recent developments in the detection and management of congenital heart disease and osteoporosis in patients with monosomy X, or Turner syndrome (TS). Magnetic resonance angiography (MRA) using gadolinium as a contrast agent demonstrates a higher prevalence and greater diversity of congenital cardiovascular defects than previously recognized in TS. Almost 50% of girls and women with TS have marked tortuosity or ectasia of the aortic arch, suggesting that these individuals may be at greater risk for aneurysm formation or dissection and therefore require closer monitoring. MRA also reveals that major venous anomalies are common in TS, with partial anomalous pulmonary venous return and persistent left superior vena cava each found in about 13% of patients. MR imaging even without contrast is a valuable complement to routine cardiac ultrasound in detecting abnormalities of the aortic valve. Abnormal electrocardiographic findings, including prolongation of the QTc interval, have recently been documented in many individuals with TS. Conduction and repolarization abnormalities have not been associated with congenital anatomic defects and are as common in young girls as adults. The clinical significance of these electrophysiological findings is unknown at present, but attention to the ECG in TS is important, particularly in monitoring the QTc when prescribing drugs associated with QT prolongation. Patients with TS are at high risk for osteoporosis as a result of premature ovarian failure and intrinsic bone abnormalities specific to the syndrome. Low cortical bone mineral density (BMD) is apparent in prepubertal girls, and it remains low in adults, independent of estrogen treatment and other hormonal factors. The low mineralization of cortical bone in TS may be associated with a small increased fracture risk, but no treatments are known to increase cortical bone mineral content in TS. Trabecular BMD is normal in TS women who have received continuous estrogen treatment from their mid-teens, although areal densitometry scores may be misleadingly low in very small patients. However, young women with ovarian failure who have not received estrogen treatment for extended periods of time are at high risk for osteoporosis of trabecular bone of the spine, with associated compression fractures and height loss. Therefore, judicious management of estrogen therapy to prevent osteoporosis while minimizing estrogen-associated adverse events is a challenging aspect of care for girls and women with TS. [Copyright &y& Elsevier]

Objective: A targeted analysis with transcript data from previous research was designed to study the perceived effects of secret-keeping on individuals with Turner syndrome (TS). Study design: Girls and women (n = 97) and 21 parents participated in the initial interview study. Transcripts were coded and analyzed for constructs related to secret-keeping. Results: Thirty percent of participants spontaneously mentioned that their health care providers (HCP) or parents had withheld all or part of their TS diagnosis. Of those, 15 individuals were not informed of the infertility component of their diagnosis. Individuals reporting secret-keeping were more likely to have had a negative perception of the HCP''s role in the disclosure process compared with those participants who did not report that a secret had been kept (P < .025). Conclusion: The prevalence of secret-keeping within this sample population suggests it is likely an existing concern in the greater TS population. How HCPs disclose a TS diagnosis may affect whether secrets are kept. Conversely, secret-keeping may result in a negative disclosure experience. These observations suggest the need for interventions aimed at helping HCPs disclose health-related information to parents and their children in a timely, caring, and sensitive manner. [Copyright &y& Elsevier]

An abstract of the article " Shunt and right ventricular structural findings in isolated anomalous pulmonary venous return in Turner syndrome," by Laura Olivieri, Anjali Chelliah, Li-Yueh Hsu, Richard B. Thompson, Vladimir Bakalov, Douglas Rosing, Carolyn Bondy, and Andrew E. Arai is presented.

Abstract: Abnormalities in both quality of life and cognitive measures have been well-documented in women with Turner Syndrome (TS). Additionally, shyness and social anxiety appear to be common clinical features of TS. However, few studies have systematically examined the presence of mood and behavior syndromes in these women. In this chapter we report our recent studies on the psychological and social aspects of Turner syndrome in adult women. Overall, rates of psychiatric syndromes were not higher in women with TS than in women attending gynecologic clinics. Nonetheless, premature ovarian failure was associated with depression, reduced self-esteem and impaired social functioning. Elucidation of the specific mechanisms of this effect and identification of the women at particular risk are important areas for further study. Attention to psychological health and social functioning should be an important part of the care for women with premature ovarian failure, regardless of the underlying disorder. [Copyright &y& Elsevier]

Abstract: Apparent demineralization of the skeleton has been noted in females with Turner syndrome (TS) since the first descriptions of the disorder. Studies, using quantitative methods to measure areal bone mineral density (BMD) in TS, have often been confounded by small skeletal size and variable exposure to estrogen. Recent studies taking bone size into account suggest that BMD at skeletal sites of predominantly trabecular bone, e.g., the lumbar spine and ultra distal radius, is normal in women that have used estrogen consistently. However, these women have significantly lower than normal BMD at skeletal sites with predominantly cortical bone, e.g., the radial shaft and femoral neck. It is unknown whether the reduction in cortical BMD is an intrinsic feature of TS perhaps related to haploinsufficiency for SHOX or another X-linked gene, or due to deficient estrogen exposure during childhood and adolescence, and whether this cortical bone deficit increases fracture risk. Current recommendations to begin low dose estrogen treatment in the early teens may clarify these issues. Wide use of bisphosphonates to treat low BMD in young women with TS is not warranted since these agents have little if any effect on cortical bone while trabecular bone has excellent response to estrogens. [Copyright &y& Elsevier]

Objective: Evaluation of current clinical, experimental, genetic, and epidemiological data pertaining to the role of androgens in mammary growth and neoplasia. Design: Literature review. Setting: National Institutes of Health. Subject(s): Recent, basic, clinical, and epidemiological studies. Intervention(s): None. Main Outcome Measure(s): Effects of androgens on mammary epithelial proliferation and/or breast cancer incidence. Result(s): Experimental data derived from rodents and cell lines provide conflicting results that appear be strain- and cell line-dependent. Epidemiologic studies have significant methodological limitations and provide inconclusive results. The study of molecular defects involving androgenic pathways in breast cancer is in its infancy. Clinical and nonhuman primate studies, however, suggest that androgens inhibit mammary epithelial proliferation and breast growth and that conventional estrogen treatment suppresses endogenous androgens. Conclusion(s): Abundant clinical evidence suggests that androgens normally inhibit mammary epithelial proliferation and breast growth. Suppression of androgens by conventional estrogen treatment may thus enhance estrogenic breast stimulation and possibly breast cancer risk. Clinical trials to evaluate the impact of combined estrogen and androgen hormone replacement regimens on mammary gland homeostasis are needed to address this issue. [ABSTRACT FROM AUTHOR]

Objective: To assess fetal and maternal outcomes of pregnancies in women with Turner syndrome (TS).Design: Retrospective case series.Setting: Clinical research center.Patient(s): 276 adults with cytogenetically proven TS participating in an intramural natural history protocol.Intervention(s): None.Main Outcome Measure(s): Menstrual and obstetric histories, 50-cell karyotypes, and cardiovascular evaluation including aortic diameter measurements.Result(s): Our cohort included five women with spontaneous pregnancies and five with pregnancies using assisted reproduction (ART). All five women with spontaneous pregnancies had spontaneous puberty, despite 45,X in ≥90% of their 50-cell karyotype. Participants had a total of 13 pregnancies and 14 live births. One child had cerebral palsy; the others were chromosomally and developmentally normal. Delivery was by cesarean section in four out of seven spontaneous and six out of six ART-related pregnancies. One mother experienced preeclampsia in an ART-related twin pregnancy that required a preterm delivery; she has marked but stable aortic dilation years later.Conclusion(s): Approximately 2% of our study cohort experienced spontaneous pregnancies despite high-grade X monosomy, and a similar number achieved pregnancy via oocyte donation and ART. The potential for life-threatening cardiovascular complications warrants comprehensive screening before conception or single-embryo transfer, and caution regarding unintentional pregnancies for TS women. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To identify and characterize otolaryngologic markers for the early diagnosis of Turner syndrome (TS). Study design: Prospective cohort survey. Methods: Setting: Clinical Center of the National Institutes of Health (NIH). Patients: Ninety-one females, 7–61 years old (average=28.7 y), enrolled in a multidisciplinary study of karyotype–phenotype correlations in TS. Main outcome measures: Age at diagnosis, X chromosome karyotype, history of chronic or recurrent otitis media (OM), sensorineural hearing loss (SNHL), palate dysmorphism, pinna deformity, pterygium colli, low posterior hairline, low-set ears, and micrognathia. Results: Sixty-nine (76%) patients had a history of chronic or recurrent OM, 62 (68%) had a dysmorphic palate, 57 (63%) had SNHL, and 90 (99%) had one or more of these findings. 83 (91%; average age at diagnosis=9.4 y) had one or more external craniofacial signs: pinna abnormalities, pterygium colli, low-set ears, micrognathia or a low posterior hairline. Eight patients (average age at diagnosis=13.2 y) had no external craniofacial signs, although seven (88%) of these eight patients had a history of chronic or recurrent OM, dysmorphic palate or SNHL. The age at diagnosis was not significantly different between groups with or without external craniofacial signs (P =0.126). Conclusions: Patients with mild or incompletely penetrant TS phenotypes often present with otitis media, hearing loss, or both before the diagnosis of TS is established. Palatal dysmorphism, including ogival morphology, is another otolaryngologic marker for TS. Prompt recognition of these manifestations of TS could hasten its diagnosis and appropriate medical care. [Copyright &y& Elsevier]

Objectives: Our goal was to determine the prevalence and characteristics of aortic valve disease in girls and women with monosomy for the X chromosome, or Turner syndrome (TS). Background: Complications from congenital aortic valve disease are a major source of premature mortality in TS, but accurate data on the prevalence of aortic valve abnormalities and their association with aortic root dilation are not available. Methods: This prospective study characterized the aortic valve and proximal aorta in 253 individuals with TS age 7 to 67 years using transthoracic echocardiography as our primary screening tool, supplemented with magnetic resonance imaging. Results: Transthoracic echocardiography revealed a normal tricuspid aortic valve (TAV) in 172 and a bicuspid aortic valve (BAV) in 66 subjects. Transthoracic echocardiography could not visualize the aortic valve in 15 of 253 or 6%. Magnetic resonance imaging diagnosed 12 of 15 of these cases (8 BAV and 4 TAV), so that only 3 of 253 (1.2%) could not be visualized by either modality. The aortic valve was bicuspid in 74 of 250 (30%) adequately imaged subjects. The prevalence was equal in pediatric (<18 years, n = 89) and adult populations. Over 95% of abnormal aortic valves in TS resulted from fusion of the right and left coronary leaflets. Ascending aortic diameters were significantly greater at the annulus, sinuses, sinotubular junction, and ascending aorta in the BAV group, with aortic root dilation in 25% of subjects with BAV versus 5% of those with TAV. Conclusions: Girls and women with TS need focused screening of the aortic valve and root to identify the many asymptomatic individuals with abnormal valvular structure and/or aortic root dilation. [Copyright &y& Elsevier]