Turner Syndrome Population Research Articles

7972 A Shared Phenotype, Transcriptome, and Methylome in Turner Syndrome Across Various Karyotypes with Concurrent Chronic Neutrophil Activation

Abstract Disclosure: J. Just: None. L. Ridder: None. E. Johannsen: None. H. Christensen: None. A. Skakkebæk: None. C.H. Gravholt: None. Turner syndrome (TS) is a clinical diagnosis with a karyotype containing one X chromosome and complete or partial absence of the second X chromosome. TS is typically associated with clinical manifestations such as short stature, hypergonadotropic hypogonadism and metabolic conditions. The genome-wide changes in females with TS affect both transcriptome and methylome. Historically, genomic studies have primarily focused on the 45,X karyotype, leaving the impact of other karyotypes unexplored. Only 35-45% of the entire TS population has the 45,X karyotype, while the remaining TS women have a range of other karyotypes - i.e. 45,X/46,XX, 46,X,i(Xq), 46,X,i(Xp), 45,X/46,XY, ring X. This study aimed to bridge this gap by comparing TS individuals with the standard 45,X karyotype (TS 45,X) (n = 32) to those with alternative karyotypic forms (TS other karyotypes) (n = 24), alongside age-matched 46,XX controls (n = 33). Specifically, we analyzed the DNA methylation and gene expression profiles from whole-blood samples and explored the genetic and clinical similarities between these groups. Overall findings revealed a shared phenotype and an identical autosomal transcriptome and methylome between TS 45,X and TS other karyotypes. Furthermore, TS 45,X and TS other karyotypes shared the same expression profile for all pseudoautosomal 1 (PAR1) genes on the X chromosome. In addition, the expression of XIST from the q-arm of the X chromosome did not affect the autosomal transcriptome or methylome. Thus, the X chromosomal p-arm, and perhaps in particular PAR1, appear to be a main driver influencing the genome-wide transcriptome and methylome Combining DNA methylation, gene expression and white blood cell counts, we observed a higher neutrophil count (p < 0.01), and increased neutrophil activation in the combined TS group. The increased neutrophil activity, based on increased gene expression of neutrophil activation markers (myeloperoxidase, neutrophil elastase, S100A8/9, p < 0.01), suggested a pathological activation of neutrophils with concomitant release of pro-inflammatory mediators. We further validated the increase of neutrophils in TS women in an independent cohort using flow cytometry (p < 0.01). Emerging evidence has highlighted the substantial involvement of neutrophils in chronic inflammatory processes associated with metabolic diseases such as obesity and diabetes, which triggers a sustained low-grade inflammation partially driven by activated neutrophils. The neutrophil increase and activation in TS women may offer an explanation for this phenotypic trait observed in TS women. Therefore, identifying TS women with increased neutrophil activation in order to initiate anti-inflammatory treatment earlier could potentially mitigate the progression towards more severe metabolic disturbances and associated co-morbidities. Presentation: 6/1/2024

Assessment of aortic dilatation in Chinese children and adolescents with Turner syndrome: a single center experience

BackgroundPatients with Turner syndrome (TS) face an increased risk of developing aortic dilatation (AD), but diagnosing AD in children presents greater complexity compared to adults. This study aimed to investigate the application of various assessment indicators of AD in Chinese children and adolescents with TS.MethodsThis study included TS patients admitted to Shenzhen Children’s Hospital from 2017 to 2022. Cardiovascular lesions were diagnosed by experienced radiologists. Patients without structural heart disease were divided into different body surface area groups, then the Chinese TS population Z-score (CHTSZ-score) of the ascending aorta was calculated and compared with other indicators such as aortic size index (ASI), ratio of the ascending to descending aortic diameter (A/D ratio), and TSZ-score (Quezada’s method).ResultsA total of 115 TS patients were included, with an average age of 10.0 ± 3.7 years. The incidences of the three most serious cardiovascular complications were 9.6% (AD), 10.4% (coarctation of the aorta, CoA), and 7.0% (bicuspid aortic valve, BAV), respectively. The proportion of developing AD in TS patients aged ≥ 10 years was higher than that in those < 10 years old (16.6% vs. 1.8%, P = 0.009), and the proportion of patients with CoA or BAV who additionally exhibited AD was higher than those without these conditions (31.6% vs. 5.2%, P < 0.001). The ASI, A/D ratio, TSZ-score, and CHTSZ-score of the 11 patients with AD were 2.27 ± 0.40 cm/m2, 1.90 ± 0.37, 1.28 ± 1.08, and 3.07 ± 2.20, respectively. Among the AD patients, only 3 cases had a TSZ-score ≥ 2, and 2 cases had a TSZ-score ≥ 1. However, based on the assessment using the CHTSZ-score, 6 patients scored ≥ 2, and 5 patients scored ≥ 1. In contrast, the TSZ-score generally underestimated the aortic Z-scores in Chinese children with TS compared to the CHTSZ-score.ConclusionsThe applicability of ASI and A/D ratio to children with TS is questionable, and racial differences can affect the assessment of TSZ-score in the Chinese population. Therefore, establishing the CHTSZ-score specifically tailored for Chinese children and adolescents is of paramount importance.

Risk assessment for aortic dissection in Turner syndrome: The role of the aortic growth rate.

The risk of aortic dissection (AoD) is increased in Turner syndrome (TS) but predicting those at risk is difficult. Based on scarce evidence, preventive aortic surgery is recommended when aortic diameter increases >5 mm/year.To investigate the aortic growth rate in TS and TS-related conditions associated with aortic growth. We also reported our experience of women who suffered aortic dissection (AoD), and who had preventive aortic replacement. 151 adult TS were retrospectively identified. Women who had more than one transthoracic echocardiogram (TTE) after age 16 years were included in the aortic growth study. Aortic diameters at sinuses of Valsalva (SoV) and ascending aorta (AA) were analysed by two experts. 70/151 women had more than one TTE (interscan interval 4.7 years). Mean aortic growth was 0.13 ± 0.59 mm/year at SoV and 0.23 ± 0.82 mm/year at AA. Known risk factors for aortic dilatation and TS-related conditions were not associated with aortic growth. 4/151 women experienced AoD (age 25±8 years): two had paired scans for aortic growth, which was 0.67 mm/year at both SoV and AA in the first woman, and 11 mm/year (SoV) and 4 mm/year (AA) in the second. Only 1/4 of women with AoD survived; she used a TS cardiac-alert card to inform emergency personnel about her risk of AoD. 5/151 had a preventive aortic replacement, but one died post-operatively. Mean aortic growth in our TS population was increased compared to non-TS women and was not associated with currently known risk factors for AoD, suggesting that aortic growth rate itself could be a useful variable to stratify who is at risk for AoD.

Dermatological concerns for women and girls with turner syndrome.

Turner syndrome (TS) is associated with distinct manifestations in women and girls including short stature, cardiac abnormalities, premature ovarian failure as well as dermatological features, including lymphedema, keloids, onychodystrophy, and acne. Although many dermatological concerns present during the first few decades of life, the overwhelming majority of respondents are not provided with dermatology referrals at diagnosis. This cross-sectional study utilized an author designed survey to assess self-reported dermatological manifestations, dermatology referral experience, common therapies for select dermatological conditions, as well as a validated 10-question Dermatology Life Quality Index (DLQI) to assess quality-of-life impact in women and girls with Turner syndrome. In our cohort, 64% (n = 149) had been referred to a dermatologist at some point in their life time. The majority of individuals self-identified their dermatological concern (79.6%) and were referred after a dermatological concern had already occurred (90.2%). The most common dermatological findings reported were xerosis cutis (78.7%), lymphedema (73%), and more than 20 acquired melanocytic nevi (70%). The overall mean DLQI score was 3.52, indicative of a small effect on the patient's life. Onychodystrophy, history of skin biopsy, and lymphedema were statistically significant to have a higher impact on quality of life. Our data reveal that skin conditions are highly prevalent in the TS population during the early decades of life and affirm utilizing these conditions in the TS diagnostic process, as well as emphasize the need for specialized dermatology referrals to address the detrimental impacts related to skin concerns on quality of life.

Hyperglycemia in Turner syndrome: Impact, mechanisms, and areas for future research.

Turner syndrome (TS) is a common chromosomal disorder resulting from complete or partial absence of the second sex chromosome. Hyperglycemia, ranging from impaired glucose tolerance (IGT) to diabetes mellitus (DM), is common in TS. DM in individuals with TS is associated with an 11-fold excess in mortality. The reasons for the high prevalence of hyperglycemia in TS are not well understood even though this aspect of TS was initially reported almost 60 years ago. Karyotype, as a proxy for X chromosome (Xchr) gene dosage, has been associated with DM risk in TS - however, no specific Xchr genes or loci have been implicated in the TS hyperglycemia phenotype. The molecular genetic study of TS-related phenotypes is hampered by inability to design analyses based on familial segregation, as TS is a non-heritable genetic disorder. Mechanistic studies are confounded by a lack of adequate TS animal models, small and heterogenous study populations, and the use of medications that alter carbohydrate metabolism in the management of TS. This review summarizes and assesses existing data related to the physiological and genetic mechanisms hypothesized to underlie hyperglycemia in TS, concluding that insulin deficiency is an early defect intrinsic to TS that results in hyperglycemia. Diagnostic criteria and therapeutic options for treatment of hyperglycemia in TS are presented, while emphasizing the pitfalls and complexities of studying glucose metabolism and diagnosing hyperglycemia in the TS population.

Prevalence and development of aortic dilation and dissection in women with Turner syndrome: a systematic review and meta-analysis

Objectives Women with Turner syndrome (TS) have an increased risk of aortic disease, reducing their life-expectancy. This study aimed to systematically review the prevalence of thoracic aortic dilatation, aortic dimensions and growth, and the incidence of aortic dissection in adult TS women. Methods A systematic literature search was conducted up to July 2022. Observational studies with an adult TS population were included, studies including children aged < 15 years old or a specific TS population were excluded. Results In total 21 studies were included. The pooled prevalence of ascending aortic dilatation was 23% (95%CI 19-26) at a mean pooled age of 29 years (95%CI 26-32), while the incidence of aortic dissection was 164 per 100.000 patient-years (95%CI 95-284). Three reporting studies showed aortic growth over time to be limited. Risk factors for aortic dilation or dissection were older age, bicuspid aortic valve, aortic coarctation and hypertension. Conclusion In adult women with TS, ascending aortic dilatation is common and the hazard of aortic dissection increased compared to the general population, whereas aortic growth is limited. Conventional risk markers do not explain all aortic dissection cases, therefore new imaging parameters and blood biomarkers are needed to improve prediction, allowing for patient-tailored follow-up and surgical decision making.

Evaluation of coronary microvascular dysfunction and risk factors in children and youth with Turner syndrome by magnetic resonance myocardial perfusion imaging.

Turner syndrome (TS) has an increased predisposition to ischaemic heart disease and the status of coronary microcirculation in TS is largely unknown. This study aims to evaluate myocardial microvascular function in TS using first-pass magnetic resonance perfusion imaging and determine significant risk factors contributing to microvascular dysfunction in the early stage. Perspective cohort study. The study cohort consisted of 67 children and youth with TS and 32 age- and gender-matched controls. Measurements Clinical characteristics, left ventricle (LV) volume and functionand cardiovascular magnetic resonance-derived myocardial perfusion parameters were assessed. Univariable and multivariable linear regression analyses were performed to assess the potential risk factors for microvascular dysfunction. Microvascular perfusion decreased in TS in global and segmented myocardium as reflected in the lower upslopecor and maximum signal intensity (MaxSI) of LV myocardium compared to controls. Multivariable linear regression analysis indicated that age (β = -0.107, 95% confidence interval [CI] = -0.201 to -0.013, p = .026) and being overweight/obese (β = -1.155, CI = -2.134 to -0.176, p = .021) were independent impact factors of microvascular dysfunction. Subgroup analysis showed the upslopecor of older patients with TS decreased more significantly compared with that of normal controls. Upslopecor and MaxSI were lower in overweight/obese patients with TS than in patients with normal body mass index (BMI) and controls. Myocardial microvascular dysfunction can occur in children and youth patients with TS. Age and overweight/obesity were the independent risk factors of microvascular dysfunction, which imply the importance of lowering BMI for the prevention of coronary heart disease in young TS population.

The prevalence of hypertension in paediatric Turner syndrome: a systematic review and meta-analysis.

Cardiovascular related deaths account for over 40% of the excess mortality in Turner syndrome (TS). Hypertension, a modifiable risk factor for both aortic dilatation and dissection, is more commonly encountered in TS during childhood and adolescence. Treatment of hypertension is currently recommended beyond the age of 16 years in TS to help reduce the risk of aortic dissection. This study aims to determine the prevalence of hypertension in paediatric patients with TS and explore the associated methodologies of blood pressure evaluation reported in these studies. Three online databases were searched (Medline, Embase and Web of Science) for literature which reported a prevalence, or allowed calculation of prevalence, of hypertension in patients with TS who were 18 years of age or younger. Seventeen studies which met the primary eligibility criteria, with a total of 1948 patients, were included. The estimated pooled prevalence of hypertension in children and adolescents with TS was 16% (95% CI: 8.9-24.6%). There was significant heterogeneity detected between the studies. The prevalence of hypertension in those studies which assessed 24-h Ambulatory Blood Pressure Monitoring (ABPM) was 21.1% (95% CI: 15.2-27.6%) compared those which used another method of blood pressure measurement which was 13.5% (95% CI: 5.2-24.4%). Given the impact of hypertension with long-term health outcomes and the reversibility of these same outcomes by addressing abnormal blood pressure, prompt and early diagnosis of hypertension in young girls with TS should be prioritised. We recommend the use of 24-h ABPM in screening for hypertension in the paediatric TS population.

Evaluation of cardiovascular disease in the turner syndrome population in Northern Ireland

Abstract Background There is higher frequency of both congenital heart disease and acquired cardiovascular conditions in patients with Turner syndrome. It is associated with increased early morbidity and mortality compared with the general population related mainly to cardiovascular complications. Purpose We sought to ascertain the prevalence and outcomes of cardiac abnormalities in patients with Turner syndrome in Northern Ireland. Methods Patients with Turner Syndrome who attended cardiology or gynaecology clinics in the Belfast Health and Social Care Trust were identified and demographic and clinical data were obtained. Results 165 patients who had undergone cardiovascular assessment and imaging were identified. The mean age was 38±13 years. Hypercholesterolaemia was present in 49.7%, hypertension in 21% and diabetes mellitus in 15.2%. Patients with these cardiovascular risk factors were older compared to those without (Table 1). Ischaemic heart disease was present in 2.4%. Cardiac structural abnormalities were present in 52 patients (31.5%) and bicuspid aortic valve was the most common abnormality (23.6%). 9.1% of patients had a history of cardiothoracic surgery or catheter intervention and 1 patient had a previous Type A aortic dissection surgically repaired. The variety and frequency of cardiac structural abnormalities are listed in Table 2. Conclusion The prevalence of structural cardiac abnormalities and cardiovascular risk factors in Turner patients greatly exceeds that of the general population. This highlights the need for screening with cross sectional cardiac imaging plus early identification and management of cardiovascular risk factors. Funding Acknowledgement Type of funding sources: None.

Clinical assessment of blood pressure in 60 girls with Turner syndrome compared to 1888 healthy Danish girls.

Hypertension contributes to increased risk of cardiovascular disease in patients with Turner syndrome (TS). Our objective was to evaluate blood pressure (BP) in girls with TS followed longitudinally through childhood and adolescence compared to a newly established BP reference material. Cohort study with data collected from 1991 to 2019 consisting of a population-based reference cohort and a group of girls with TS followed at a single tertiary centre. Reference population of 1888 healthy girls with 4890 BP recordings and 60 girls with TS with 365 BP recordings. Difference in diastolic BP (DBP) and systolic BP (SBP), expressed in standard deviation scores (SDS), between girls with TS and the reference population, unadjusted and adjusted for BMI. Difference in BP (SDS) between TS subgroups (karyotype, oestrogen treatment, cardiac diagnosis). The girls with TS had significantly higher DBP (mean ± SD, 0.72 SDS ± 0.95; p < .001) and SBP (0.53 SDS ± 1.11; p = .001) than the reference population. Adjusted for BMI, girls with TS had significantly higher DBP (mean ± SE, 0.71 SDS ± 0.12; p < .001) but not SBP (0.17 SDS ± 0.16; p = .29). There was no significant difference in DBP (median, IQR: 0.97 SDS, 0.30-1.58 vs. 0.76 SDS, 0.10-1.20; p = .31) or SBP (0.51 SDS, 0.15-1.30 vs. 0.57 SDS, -0.30 to 1.05; p = .67) between individuals with or without a cardiac diagnosis. In the TS population, 55% (31/56) had at least one BP recording above the hypertension threshold. Our findings indicate that standardised longitudinal routine monitoring of BP in girls with TS already in childhood is of utmost importance.

O-185 Evaluation of the decision-making process of girls with Turner syndrome and their parents considering ovarian tissue cryopreservation

Abstract Study question What are the experiences with the decision-making process of girls with Turner syndrome (TS) considering ovarian tissue cryopreservation (OTC), their parents and healthcare providers? Summary answer Offering a new option to preserve fertility in TS caused unrealistic hope leading to challenges for healthcare providers to fulfil the ideal of informed consent. What is known already Due to premature ovarian insufficiency, girls with TS have only a small chance of genetic offspring. OTC might increase these odds. Healthcare providers and scientist are still cautious in offering OTC to girls with TS because of the many uncertainties regarding OTC in this patient group. Hence, OTC is now offered to girls with TS between 2 and 18 years old in a research setting: the TurnerFertility study. Study design, size, duration A retrospective qualitative study consisting of a survey and focus groups. Within a year after counselling, families (n = 132) received a survey with 30 questions regarding their experiences with the decision-making process and also an invitation for a focus group. The focus groups were conducted between January and October 2019 and lasted 51-84 minutes. The topic lists were based on literature research and survey results. Results were analysed following a thematic analysis approach. Participants/materials, setting, methods This is a sub-study of the prospective intervention study within an academical medical centre. Focus groups were composed through purposive sampling. Focus group 1 (FG1) consisted of five gynaecologists involved in counselling, FG2 with seven paediatricians who referred girls for counselling, FG3 with nine parents of girls with TS between 2 and 12 years old and FG4 with three parents of girls with TS between 13 and 17 years old. Main results and the role of chance 90% of survey respondents appreciated counselling regarding fertility options and considered it an enrichment of existing healthcare. The individual consultation was rated as most contributing by 66% of the survey respondents, followed by the information meeting (37%) and decision aid (3%). The focus groups revealed that many had not discussed options for future parenthood with a healthcare provider before. Girls with TS and their parents indicated that the option of OTC raised hope for future genetic offspring, and at once made them feel like they had no choice but to take this chance. The small chance of success did not influence the decision for families who opted for OTC. Some parents who had to decide for their young daughter accepted OTC to give their daughter the option to decide herself whether to make use of the cryopreserved tissue later in life. Gynaecologists found it challenging to truly make families grasp a realistic perspective of OTC in TS and the associated mental and physical risks. Gynaecologists and paediatricians struggled with conflicting moral principles of non-maleficence against respect for autonomy: healthcare providers recognized the scientific relevance for the TS population, while it felt inconsistent with the disproportionate burden for some individual patients. Limitations, reasons for caution Because there was no validated survey for this topic in TS, we developed a survey based on literature research and experiences of a dedicated TS team. Among the survey responders and focus group participants a greater proportion decided for OTC compared to the overall counselled group (75% vs 60%). Wider implications of the findings This study gives insight in the issues to consider when implementing new technologies regarding fertility, in which parents have to decide for their child, where it is expected that anticipated decision regret plays a major role, or where healthcare providers experience conflicting duties as scientist and physician. Trial registration number not applicable

The Population Prevalence, Thyroid Cancer and Mortality Risk for Turner Syndrome in South Korea Based on National Health Insurance Service (NHIS) Data

Background: In the present study, we estimated the population prevalence, cancer and mortality risk for Turner syndrome (TS) using data from National Health Insurance Service (NHIS) and Rare Diseases Registry (RDR). Methods: We collected data on subjects with TS who were registered in the RDR between 2012 and 2017. To estimate cancer and mortality risk of TS, the data of TS subjects were compared with and 1:5 age and sex matched controls. Results: In 2017, 2054 individuals with TS were identified out of the total population of 26,249,201 South Korean females and the prevalence was 7.83 per 100,000 persons. In 2017, the distributions of TS prevalence across 10 year old age groups showed 11.44 per 100,000 persons in the group under the age of 10 years, 22.43 per 100,000 persons in teenagers, 18.40 per 100,000 persons in twentieth, 10.24 per 100,000 persons in thirtieth, 4.05 per 100,000 persons in fortieth and 0.39 per 100,000 persons after fiftieth. During 5.3 years, the cancer risk in patients with TS was higher than that of age matched controls [hazard ratio (HR) = 1.813, 95% CI 1.009-3.257]. When cancer is categorized by each organs, thyroid cancer risk in patients with TS was significantly higher than that of age matched controls [hazard ratio (HR) =2.697, 95% CI 1.025-7.097]. The all cause of mortality risk of TS was higher than that of age matched controls [hazard ratio (HR) =3.421, 95% CI 1.623-7.212]. Conclusions: In South Korea, the TS population prevalence was 7.83 per 100,000 persons in 2017. The subjects with TS have higher thyroid cancer and mortality risk than healthy controls. Key words: Prevalence, Turner syndrome, thyroid cancer risk, mortality risk.

44. Abnormal Uterine Bleeding during Pubertal Induction with Transdermal Estrogen in Turner Syndrome: Experience from a Large Turner Syndrome Center

<h3>Background</h3> More than 80% of girls with Turner syndrome (TS) experience primary ovarian failure prior to the onset of menarche. Hormone replacement therapy (HRT) is recommended to start between 11-12 years of age, followed by titration to adult dosing over 18-24 months. Current guidelines recommend that HRT starts with transdermal estradiol, followed by the addition of oral progesterone once breakthrough bleeding occurs or after 18-24 months of unopposed estrogen therapy, whichever occurs first. In our TS population, several individuals have experienced abnormal uterine bleeding (AUB) while undergoing pubertal induction with transdermal estradiol. The objective of this study was to identify risk factors associated with and evaluate the management practices of AUB during pubertal induction among females with TS. <h3>Methods</h3> A retrospective case series of 45 TS females seen between January 2007 and June 2019 . Among these, 64% (n=29) served as controls and 55% (n=16) experienced AUB. <h3>Results</h3> Several risk factors for the development of AUB were identified: frequency of progestin cycling less than monthly (56.5% for cases vs. 0% for control), prolonged duration of unopposed estrogen (median of 21 months for cases vs. 17 months for controls), low dose (<200 mg) of progestin (50% of cases vs. 13.5% of control), and noncompliance with HRT (18.8%). Of the patients who experienced AUB, 3 received an additional 10 day course of progestins, 7 were treated by increasing their progestin dose, 6 were switched to another method of HRT (e.g. IUD or OCP), 6 increased cycling frequency to monthly, 4 required hospitalization, 2 required iron supplementation, and 2 required a transfusion with blood products. <h3>Conclusions</h3> Based on our experience, we recommend the following to prevent AUB during pubertal induction with transdermal estrogen in TS girls: 1) Cycle with progestins monthly, 2) Introduce progestins at the onset of breakthrough bleeding or at 18 months, whichever occurs first, 3) Use progestin dosing at the upper end of the recommended range (e.g. 200 mg for micronized progesterone) 4) Counsel all patients regarding the risk of AUB, 5) Monitor all patients regularly during pubertal induction, 6) Monitor with heightened surveillance those patients who show rapid development of secondary sex characteristics on low dose estrogen.

Heart and Turner syndrome

Turner syndrome (TS) is a rare disease (ORPHA #881) which affects about 50 in 100 000 newborn girls. Their karyotype shows a complete or partial loss of the second X chromosome. In TS, congenital cardiovascular malformations, such as bicuspid aortic valves and aortic coarctation are frequent, affecting 20-30% and 7-18% of the TS population, respectively. The morbidity and mortality of these patients are high and related to the presence of hypertension and/or aortic dilatation (40%), inducing aortic dissection. European guidelines published in 2017 have indicated how to monitor patients using magnetic resonance imaging (MRI) and/or echography. Different studies have shown that a cardiovascular lifelong follow-up is necessary and therefore education of patients with TS and their families represents a major issue. This review will present recent data concerning the progression of aortic diameters as well as current molecular knowledge of the cardiovascular system in patients with TS.

Levonorgestrel correlates with less weight gain than other progestins during hormonal replacement therapy in Turner Syndrome patients

Turner Syndrome (TS) is associated with an increased risk of cardiovascular and metabolic complications. Furthermore, TS women need hormone replacement therapy (HRT), of which progestins can influence body weight. We aimed to analyze the metabolic and weight profile in a cohort of 111 TS women. They started receiving estrogen at 15.8 (±3.6) years old, with no change in hypertension, dysglycemia, and dyslipidemia incidence but with a tendency to increase overweight (p = 0.054). As the first used type of progestin, most had received cycles of 10 days per month of medroxyprogesterone (MPA) or levonorgestrel (LNG), then shifted to micronized progesterone (MP), which has currently become the most used one. By multiple linear regression analysis, we found that the prolonged use of MPA, LNG, or MP showed no metabolic change except for weight gain. The percentage of annual BMI increment was positive for all progestins used in TS women (MPA 2.2 ± 2.2; LNG 0.2 ± 1.2; and MP 2.2 ± 2.6 kg/m2), but LNG seemed to best prevent on weight gain over time (p < 0.05). In conclusion, metabolic comorbidities are prevalent in TS even before the HRT regimen, and LNG performed better on less weight gain than MPA and MP in our cohort of the TS population.

Turner syndrome in diverse populations.

Turner syndrome (TS) is a common multiple congenital anomaly syndrome resulting from complete or partial absence of the second X chromosome. In this study, we explore the phenotype of TS in diverse populations using clinical examination and facial analysis technology. Clinical data from 78 individuals and images from 108 individuals with TS from 19 different countries were analyzed. Individuals were grouped into categories of African descent (African), Asian, Latin American, Caucasian (European descent), and Middle Eastern. The most common phenotype features across all population groups were short stature (86%), cubitus valgus (76%), and low posterior hairline 70%. Two facial analysis technology experiments were conducted: TS versus general population and TS versus Noonan syndrome. Across all ethnicities, facial analysis was accurate in diagnosing TS from frontal facial images as measured by the area under the curve (AUC). An AUC of 0.903 (p < .001) was found for TS versus general population controls and 0.925 (p < .001) for TS versus individuals with Noonan syndrome. In summary, we present consistent clinical findings from global populations with TS and additionally demonstrate that facial analysis technology can accurately distinguish TS from the general population and Noonan syndrome.

Changes in the cohort composition of turner syndrome and severe non-diagnosis of Klinefelter, 47,XXX and 47,XYY syndrome: a nationwide cohort study

BackgroundKnowledge on the prevalence of sex chromosome abnormalities (SCAs) is limited, and delayed diagnosis or non-diagnosis of SCAs are a continuous concern. We aimed to investigate change over time in incidence, prevalence and age at diagnosis among Turner syndrome (TS), Klinefelter syndrome (KS), Triple X syndrome (Triple X) and Double Y syndrome (Double Y).MethodsThis study is a nationwide cohort study in a public health care system. The Danish Cytogenetic Central Registry (DCCR) holds information on all karyotypes performed in Denmark since 1961. We identified all individuals in the DCCR with a relevant SCA during 1961–2014; TS: n = 1156; KS: n = 1235; Triple X: n = 197; and Double Y: n = 287. From Statistics Denmark, which holds an extensive collection of data on the Danish population, complete data concerning dates of death and migrations in and out of Denmark were retrieved for all individuals.ResultsThe prevalence among newborns was as follows: TS: 59 per 100,000 females; KS: 57 per 100,000 males; Triple X: 11 per 100,000 females; and Double Y: 18 per 100,000 males. Compared with the expected number among newborns, all TS, 38% of KS, 13% of Triple X, and 18% of Double Y did eventually receive a diagnosis. The incidence of TS with other karyotypes than 45,X (P < 0.0001), KS (P = 0.02), and Double Y (P = 0.03) increased during the study period whereas the incidence of 45,X TS decreased (P = 0.0006). The incidence of Triple X was stable (P = 0.22).ConclusionsThe prevalence of TS is higher than previously identified, and the karyotypic composition of the TS population is changing. Non-diagnosis is extensive among KS, Triple X and Double Y, whereas all TS seem to become diagnosed. The diagnostic activity has increased among TS with other karyotypes than 45,X as well as among KS and Double Y.

Evaluation of cardiac MRI and ambulatory blood pressure monitoring in a pediatric Turner syndrome population

BackgroundThe benefits of cardiac MRI in the diagnosis of cardiac abnormalities in adults with Turner syndrome (TS) have been shown by several studies. High blood pressure frequently occurs in TS patients; therefore ambulatory blood pressure monitoring (ABPM) is routinely performed in adults with TS. However, potential benefits of either technique remain undetermined in the pediatric TS population. AimsTo evaluate the potential benefits of cardiac MRI and ABPM in pediatric patients with TS. MethodsA total of 19 girls with TS, aged between 9 and 18 years old, were prospectively included in a cross-sectional study from May 2015 to November 2015. We evaluated data from both cardiac MRI and ABPM by comparison with 2D echocardiography and instant measurement of blood pressure. ResultsOf the 16 cardiac MRI performed, 4 (25%) revealed anatomical abnormalities undiagnosed by echocardiography. Our analysis demonstrated a low correlation between echocardiography and cardiac MRI in measuring diameters of the aortic root. ABPM revealed 5 cases (29.5%) of moderate hypertension, 4 of which were previously unknown. ConclusionsThis study has shown an advantage of using cardiac MRI and ABPM for diagnosing cardiovascular abnormalities in pediatric TS patients, therefore we recommend the routine use of both examinations to improve overall care and ensure a better transition into adulthood.

Selected Metabolic Markers in Girls with Turner Syndrome: A Pilot Study.

Background Turner syndrome (TS) predisposes an individual to obesity and related metabolic disorders. As the TS population is at a higher risk of cardiovascular diseases and malformations, research into laboratory markers of metabolic complications has been ongoing. Special significance has recently been attributed to matrix metalloproteinases (MMPs), their inhibitors (TIMPs), and neurotrophic factors, such as BDNF and GDNF. Objective To establish whether cardiometabolic risk in patients with TS is reflected in the concentrations of metalloproteinases and neurotrophic factors. Method The concentrations of circulating MMP-1, MMP-2, MMP-9, TIMP-1, BDNF, GDNF, and VEGF were measured in 17 patients with TS. The control group was composed of 11 girls with nonpathologic short stature and normal karyotype. Results There were no differences in chronological or bone age. No significant differences were observed in mean weight, although the Z-score BMI was higher in the study group. The mean baseline values of MMP-1 and BDNF were significantly lower in the control group than in the study group (p < 0.001, p = 0.001). Regression analysis revealed a positive correlation between MMP-1 concentrations and Z-score BMI (r = 0.36, p = 0.047) and between BDNF and Z-score BMI (r = 0.48, p = 0.013). Conclusion Our pilot study showed that MMP-1 may be a potential indicator of a higher risk of cardiometabolic complications in girls with TS. The elevated concentrations of BDNF in normal-weight girls with TS need to be studied further, taking into consideration the influence of estrogen-androgen imbalance.

PO13-56 - Evaluation of cardiac MRI and ambulatory blood pressure monitoring in a pediatric Turner syndrome population

Abstract Background The benefits of cardiac MRI in the diagnosis of cardiac abnormalities in adults with Turner syndrome (TS) have been shown by several studies. High blood pressure frequently occurs in TS patients; therefore ambulatory blood pressure monitoring (ABPM) is routinely performed in adults with TS. However, potential benefits of either technique remain undetermined in the pediatric TS population. Aims To evaluate the potential benefits of cardiac MRI and ABPM in pediatric patients with TS. Methods A total of 19 girls with TS, aged between 9 and 18 years old, were prospectively included in a cross-sectional study from May 2015 to November 2015. We evaluated data from both cardiac MRI and ABPM by comparison with 2D echocardiography and instant measurement of blood pressure. Results Of the 16 cardiac MRI performed, 4 (25%) revealed anatomical abnormalities undiagnosed by echocardiography. Our analysis demonstrated a low correlation between echocardiography and cardiac MRI in measuring diameters of the aortic root. ABPM revealed 5 cases (29.5%) of moderate hypertension, 4 of which were previously unknown. Conclusions This study has shown an advantage of using cardiac MRI and ABPM for diagnosing cardiovascular abnormalities in pediatric TS patients, therefore we recommend the routine use of both examinations to improve overall care and ensure a better transition into adulthood.