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Turner syndrome (TS), caused by complete or partial loss of the second sex chromosome, is associated with complex medical manifestations. The TS community identifies anxiety as a major contributor to reduced quality of life. The study aimed to improve understanding of anxiety symptomatology, diagnosis, and care in individuals with TS. A mixed methods design integrated community engagement, including community leaders as co-investigators and a community advisory board, an online survey (N = 135), and in-depth interviews (N = 10). The majority of respondents reported that anxiety symptoms occur two or more days per week, with self-advocates reporting more frequent symptoms than caregivers (p = 0.03). Self-advocates reported feeling anxious more often at school/work; both rater groups reported anxiety-related behaviors were most likely to be expressed at home. Insomnia was the most common symptom of anxiety endorsed across age and rater groups (>70%). Anxiety symptoms and triggers changed with age and often were undiagnosed or untreated during childhood. Therapy and medication were reported as helpful by most respondents who had tried these strategies. Qualitative themes included: 'Triggers for anxiety are related to TS', 'Anxiety impacts the whole family', and 'Opportunities for early identification and intervention'., (© 2024 Wiley Periodicals LLC.)

Objective: To assess national-level trends, characteristics, and outcomes of pregnancies with Turner syndrome in the United States., Design: Cross-sectional study., Setting: The Healthcare Cost and Utilization Project's National Inpatient Sample., Subjects: A total of 17,865,495 hospital deliveries from 2016-2020., Exposure: A diagnosis of Turner syndrome, identified according to the World Health Organization's International Classification of Disease 10th revision code of Q96., Main Outcome Measures: Obstetrics outcomes related to Turner syndrome, assessed with inverse probability of treatment weighting cohort and multivariable binary logistic regression modeling., Results: The prevalence of pregnant patients with Turner syndrome was 7.0 per 100,000 deliveries (one in 14,235). The number of hospital deliveries with patients who have a diagnosis of Turner syndrome increased from 5.0 to 11.7 per 100,000 deliveries during the study period (adjusted-odds ratio [aOR] for 2020 vs. 2016; 2.18, 95% confidence interval [CI] 1.83-2.60). Pregnant patients with Turner syndrome were more likely to have a diagnosis of pregestational hypertension (4.8% vs. 2.8%; aOR 1.65; 95% CI 1.26-2.15), uterine anomaly (1.6% vs. 0.4%; aOR, 3.01; 95% CI 1.93-4.69), and prior pregnancy losses (1.6% vs. 0.3%; aOR 4.70; 95% CI 3.01-7.32) compared with those without Turner syndrome. For the index obstetric characteristics, Turner syndrome was associated with an increased risk of intrauterine fetal demise (10.9% vs. 0.7%; aOR 8.40; 95% CI 5.30-13.30), intrauterine growth restriction (8.5% vs. 3.5%; aOR 2.11; 95% CI 1.48-2.99), and placenta accreta spectrum (aOR 3.63; 95% CI 1.20-10.97). For delivery outcome, pregnant patients with Turner syndrome were more likely to undergo cesarean delivery (41.6% vs. 32.3%; aOR 1.53; 95% CI 1.26-1.87). Moreover, the odds of periviable delivery (22-25 weeks: 6.1% vs. 0.4%; aOR 5.88; 95% CI 3.47-9.98) and previable delivery (<22 weeks: 3.3% vs. 0.3%; aOR 2.87; 95% CI 1.45-5.69) were increased compared with those without Turner syndrome., Conclusions: The results of contemporaneous, nationwide assessment in the United States suggest that although pregnancy with Turner syndrome is uncommon this may represent a high-risk group, particularly for intrauterine fetal demise and periviable delivery. Establishing a society-based approach for preconception counseling and antenatal follow-up would be clinically compelling., Competing Interests: Declaration of Interests Z.S.A. has nothing to disclose. A.D.M. has nothing to disclose. L.S.A. has nothing to disclose. R.S.M. has nothing to disclose. K.V.E. has nothing to disclose. S.M. received research funding from Merck. D.B. has nothing to disclose. R.J.P. has nothing to disclose. J.G.O. has nothing to disclose. K.M. has nothing to disclose., (Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article.

Background: The clinical features of Turner syndrome (TS) involve multiple organ system dysplasia, among which growth retardation and gonadal dysplasia are the most important clinical phenotypes., Methods: G banding karyotype analysis, chromosome microarray (CMA), and fluorescence in situ hybridization (FISH) were used for prenatal diagnosis of fetal chromosomes., Results: The result of fetal chromosome karyotype analysis was 46,XX. CMA showed arr[GRCh38]Xp22.33 p22.13(251888&#95;18176046)x1,Xq27.1q28(140998347&#95;156003433)x3. FISH indicated that the short arm end fragment of X chromosome was monomer and the long arm end fragment was trisomy., Conclusions: The fetal chromosome karyotype was normal, but CMA indicated that there was deletion and duplication of X chromosome. FISH verified the CMA results, locating the deletion and duplication fragments. CMA and FISH make up for the shortcomings of chromosome karyotype analysis technique. It is suggested that multiple detection methods should be applied in genetic prenatal diagnosis.

Turner syndrome (TS) affects 50 per 100 000 females. TS affects multiple organs through all stages of life, necessitating multidisciplinary care. This guideline extends previous ones and includes important new advances, within diagnostics and genetics, estrogen treatment, fertility, co-morbidities, and neurocognition and neuropsychology. Exploratory meetings were held in 2021 in Europe and United States culminating with a consensus meeting in Aarhus, Denmark in June 2023. Prior to this, eight groups addressed important areas in TS care: (1) diagnosis and genetics, (2) growth, (3) puberty and estrogen treatment, (4) cardiovascular health, (5) transition, (6) fertility assessment, monitoring, and counselling, (7) health surveillance for comorbidities throughout the lifespan, and (8) neurocognition and its implications for mental health and well-being. Each group produced proposals for the present guidelines, which were meticulously discussed by the entire group. Four pertinent questions were submitted for formal GRADE (Grading of Recommendations, Assessment, Development and Evaluation) evaluation with systematic review of the literature. The guidelines project was initiated by the European Society for Endocrinology and the Pediatric Endocrine Society, in collaboration with members from the European Society for Pediatric Endocrinology, the European Society of Human Reproduction and Embryology, the European Reference Network on Rare Endocrine Conditions, the Society for Endocrinology, and the European Society of Cardiology, Japanese Society for Pediatric Endocrinology, Australia and New Zealand Society for Pediatric Endocrinology and Diabetes, Latin American Society for Pediatric Endocrinology, Arab Society for Pediatric Endocrinology and Diabetes, and the Asia Pacific Pediatric Endocrine Society. Advocacy groups appointed representatives for pre-meeting discussions and the consensus meeting., Competing Interests: Conflict of interest: F. A.-N., N.H.A., H.B.A., C.M.B., Å.B., N.M.B., A.D., V.E., S.G., K. de G., C.H., C.H.-L., T.I., E.B.J., A.T.M.-G., K.H.M., L.N., M.N., S.R.P., L.O.R., D.S., R.J.S., A.S., K.S., H.T., F.V., M.H.V. and B.V.W. have no potential conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Endocrinology.)

Background: Turner syndrome is a genetic disorder that occurs in female individuals and is characterized by the absence of 1 of the X chromosomes. This study examined the risk of cardiovascular disease and inpatient clinical outcomes in patients with Turner syndrome., Methods: Data were extracted from the Nationwide Inpatient Sample 2016 database. Propensity score analysis was used to match women with Turner syndrome and women without Turner syndrome admitted to a hospital in the same year to evaluate the risk of cardiovascular disease and inpatient clinical outcomes in patients with Turner syndrome., Results: After 1:1 matching, 710 women with Turner syndrome and 710 women without Turner syndrome were included in the final analysis. Compared with women without Turner syndrome, women with Turner syndrome were more likely to have a bicuspid aortic valve (9.4% vs 0.01%; P < .01), coarctation of the aorta (5.8% vs 0.3%; P < .01), atrial septal defect (6.1% vs 0.8%; P < .01), and patent ductus arteriosus (4.6% vs 0.6%; P < .01). Patients with Turner syndrome were more likely to have an aortic aneurysm (odds ratio [OR], 2.46 [95% CI, 1.02-5.98]; P = .046), ischemic heart disease (OR, 1.66 [95% CI, 1.10-2.5]; P = .02), heart failure (OR, 3.15 [95% CI, 1.99-4.99]; P < .01), and atrial fibrillation or flutter (OR, 2.48 [95% CI, 1.42-4.34]; P < .01). Patients with Turner syndrome were more likely to have pulmonary arterial hypertension (OR, 2.12 [95% CI, 1.08-4.14]; P = .03) and acute kidney injury (OR, 1.60 [95% CI, 1.06-2.42]; P = .03) and to require mechanical ventilation (OR, 1.66 [95% CI, 1.04-2.68]; P = .04)., Conclusion: Turner syndrome is associated with an increased rate of cardiovascular disease and inpatient complications. These findings suggest that patients with Turner syndrome should be screened and monitored closely for cardiovascular disease and inpatient complications., (© 2024 The Authors. Published by The Texas Heart Institute®.)

Turner syndrome (TS) is a genetic condition occurring in ~1 in 2000 females characterized by the complete or partial absence of the second sex chromosome. TS research faces similar challenges to many other pediatric rare disease conditions, with homogenous, single-center, underpowered studies. Secondary data analyses utilizing electronic health record (EHR) have the potential to address these limitations; however, an algorithm to accurately identify TS cases in EHR data is needed. We developed a computable phenotype to identify patients with TS using PEDSnet, a pediatric research network. This computable phenotype was validated through chart review; true positives and negatives and false positives and negatives were used to assess accuracy at both primary and external validation sites. The optimal algorithm consisted of the following criteria: female sex, ≥1 outpatient encounter, and ≥3 encounters with a diagnosis code that maps to TS, yielding an average sensitivity of 0.97, specificity of 0.88, and C-statistic of 0.93 across all sites. The accuracy of any estradiol prescriptions yielded an average C-statistic of 0.91 across sites and 0.80 for transdermal and oral formulations separately. PEDSnet and computable phenotyping are powerful tools in providing large, diverse samples to pragmatically study rare pediatric conditions like TS., (© 2023 Wiley Periodicals LLC.)

45,X/46,XY chromosomal mosaicism presents a range of clinical manifestations, including phenotypes from Turner syndrome through genital abnormalities to apparently unaffected phenotypic males; however, the full clinical spectrum has not yet been fully delineated since prior studies on the clinical phenotype and associated risk of gonadal tumors included small cohorts and limited follow-up. To better describe the clinical manifestations and long-term outcome of patients with 45,X/46,XY mosaicism. We conducted a retrospective chart review of patients with 45,X/46,XY from three health centers (Hospital for Sick Children and Mount Sinai Hospital in Canada, and University of Pittsburgh Medical Center in United States). Of 100 patients with 45,X/46,XY karyotype, 47 were raised as females and 53 as males. Females were significantly shorter than males (p = 0.04) and height Z-score was significantly decreased with age for both genders (p = 0.02). Growth hormone (GH) treatment did not result in a significant height increase compared to the untreated group (p = 0.5). All females required puberty induction in contrast to majority of males. Five females were diagnosed with gonadal tumors, while no males were affected. Around 58% of patients exhibited at least one Turner syndrome stigmata. This study expands the clinical spectrum, long-term outcomes, and associated tumor risk in a large cohort of patients with 45,X/46,XY mosaicism. Additionally, it highlights our experience with GH therapy and prophylactic gonadectomy., (© 2023 Wiley Periodicals LLC.)

Objective: To explore the impact of maternal factors on the false-positive fetal sex chromosome aneuploidies (SCAs) results obtained through noninvasive prenatal screening (NIPS)., Methods: We retrospectively analyzed pregnant women with high-risk SCAs as revealed using NIPS between January 2017 and December 2022. Clinical data such as results of invasive prenatal diagnoses, copy number variation sequencing (CNV-seq) and pregnancy outcomes were analysed., Results: Overall, 177 (0.6 %) women with SCA-positive results were collected from 27,941 patients who had undergone NIPS. Among them, 110 (62.2 %) pregnant women chose prenatal diagnosis and 39 (35.5 %) cases were confirmed. For the women with monosomy X false-positive results from the NIPS, 53.1 % (17/32) were found to be maternal mosaicism monosomy X. In cases with 47, XXX false-positive results, 60 % (6/10) of them were maternal 47,XXX (5 cases) or maternal mosaicism 47,XXX (1 case). One (1/6, 16.7 %) case of maternal mosaicism monosomy X was detected in the false positive results of 47, XXY/47, XYY revealed. The incidence rate of maternal sex chromosome abnormalities was positively correlated with the Z-score of ChrX. When the Z-score of ChrX ≥ 15, more than 50 % of pregnant women were found to be maternal sex chromosome abnormalities, and when Z-score ≥ 30, the incidence rate was as high as 100 %., Conclusions: Maternal monosomy X mosaicism and trisomy X respectively played an important role in the discordance of 45, X and 47, XXX revealed by NIPS. CNV-seq was recommended for the pregnant women at risk of maternal sex chromosome abnormalities, which could help clinicians to provide more accurate and efficient advice during genetic counseling and to guide appropriate prenatal diagnosis strategy for the next pregnancy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Inspiring New Science to Guide Healthcare in Turner Syndrome (InsighTS) Registry is a national, multicenter registry for individuals with Turner syndrome (TS) designed to collect and store validated longitudinal clinical data from a diverse cohort of patients with TS. Herein, we describe the rationale, design, and approach used to develop the InsighTS registry, as well as the demographics of the initial participants to illustrate the registry's diversity and future utility. Multiple stakeholder groups have been involved from project conceptualization through dissemination, ensuring the registry serves the priorities of the TS community. Key features of InsighTS include recruitment strategies to facilitate enrollment of participants that appropriately reflect the population of individuals with TS receiving care in the US, clarity of data ownership and sharing, and sustainability of this resource. The registry gathers clinical data on diagnosis, treatment, comorbidities, health care utilization, clinical practices, and quality of life with the goal of improving health outcomes for this population. Future directions include multiple patient-centered clinical-translational research projects that will use the InsighTS platform. This thorough and thoughtful planning will ensure InsighTS is a valuable and sustainable resource for the TS community for decades to come., (© 2023 Wiley Periodicals LLC.)

Turner syndrome (TS) is one of the most common sex chromosomal abnormalities affecting girls and women. Diagnosis of this condition can be delayed due to a variation in clinical presentation, although an early age at diagnosis is important for several reasons. It enables psychosocial support for girls and their parents; early initiation of growth hormone therapy; puberty induction at an appropriate age; early recognition of comorbidities, such as cardiac or renal abnormalities; and timely removal of the gonads in girls with Y-chromosomal material, who are at risk for gonadoblastoma. By increasing the knowledge of health care professionals and implementing screening programs for girls with short stature, delayed puberty and/or congenital heart disease such as coarctation of the aorta, more girls might be diagnosed at an early age. This allows for lifelong follow up, which is indicated to prevent morbidity and mortality in the long term.

Introduction: Individuals with Turner syndrome (TS) are at increased risk of developing diabetes mellitus (DM). Currently, annual DM screening with hemoglobin A1c (HbA1c) with or without fasting blood glucose (FBG) is recommended starting at age 10. However, the optimal DM screening for individuals with TS is not known. The purpose of this study was to evaluate the correlation between HbA1c, FBG, and the 2-h oral glucose tolerance test (OGTT). A second goal was to query whether optimal HbA1c and FBG cut points for TS-associated DM and impaired glucose tolerance (IGT), as defined by the OGTT 2-h blood glucose (BG), might differ from those for the general population., Methods: Individuals with TS ≥ age 10 from the TS: Genotype Phenotype study in the National Institute of Child Health and Human Development's Data and Specimen Hub (DASH) who had 2-h OGTT BG, HbA1c, and FBG were included. Correlations between HbA1c, FBG, and 2-h OGTT BG were evaluated. Areas under the receiver operative characteristic (ROC-AUC) curves were generated. Optimal cut points for predicting TS-associated IGT (2-h BG ≥7.77 mmol/L) and DM (2-h BG ≥11.10 mmol/L) were determined., Results: 348 individuals had complete data (2-h OGTT BG &lt;7.77 mmol/L, n = 239; TS-associated IGT, n = 79; DM, n = 30). ROC-AUC was poor for HbA1c to predict IGT (0.57, 0.49-0.65) but better for DM (0.81, 0.71-0.90). ROC-AUC was also poor for FBG to predict IGT (0.63, 0.56-0.70) but better for DM (0.85, 0.77-0.93). At a cut point of 38 mmol/mol (5.6%), HbA1c had 67% sensitivity (95% CI: 47-83%) and 86% specificity (95% CI: 82-90%) for identifying TS-associated DM defined by 2-h OGTT BG., Conclusions: The correlation of HbA1c and 2-h OGTT BG is lower in TS than in other published studies regarding type 2 DM. HbA1c is fairly specific for DM in TS but lacks sensitivity, especially at currently utilized levels. Future research should focus on characterizing individuals with TS whose glycemic status is discordant, as this may provide additional insights into the pathophysiology of glucose metabolism in TS. Longitudinal assessment of glycemia as it relates to micro- and macrovascular complications in individuals with TS will further inform DM screening in this population., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article.

When properly treated, congenital hypothyroidism (CH) allows normal growth. We describe the case of a girl followed-up for CH diagnosed upon newborn screening, with good adherence to L-T4 therapy, who had an impaired linear growth starting from 4 years of age. Diagnostic work-up allowed exclusion of inflammatory diseases and/or malabsorption and led to the diagnosis of Turner syndrome (TS). Recombinant GH (rGH) therapy was undertaken with satisfactory growth recovery. At the age of 8, a condition of autoimmune thyroiditis was detected, due to an increased risk in the context of her syndrome. Except for small adjustments in the dose of L-T4, hypothyroidism remained well-controlled even after starting rGH therapy.

Objective: To demonstrate the prevalence of maternal mosaic monosomy X (MMXO) in a cohort of pregnant women in Vietnam., Methods: All 105,594 singleton pregnant women undergoing noninvasive prenatal screening (NIPS) between January 2019 and February 2021 in Vietnam were analyzed by measuring discordance between size- and count-based z-scores for chromosome X (ChrX) to identify suspected cases of MMXO and validated by fluorescence in situ hybridization (FISH) on maternal blood., Results: We identified 295 (0.279%) suspected MMXO cases. After FISH analysis, MMXO was confirmed in 125 cases (42.37%), revealing the MMXO prevalence of 0.118% (95% CI: 0.097-0.139%) in this cohort., Conclusion: We found a relatively high prevalence of MMXO in Vietnamese pregnant women and demonstrated a strong influence of MMXO on the ChrX z-score using a count-based method, resulting in false positives. The size-based method is not sensitive to MMXO and therefore achieves higher PPV.

Objective: To evaluate which girls with Turner syndrome (TS) could benefit from fertility preservation by ovarian tissue cryopreservation on the basis of karyotype, puberty status, and hormonal data., Design: Prospective intervention study; participants were included between 2018 and 2020., Setting: Tertiary hospital in the Netherlands., Patients: In total, 106 girls with TS aged between 2 and 18 years were included. Girls with minor X chromosome deletions, Y chromosomal content, active infections, or contraindications for surgery were excluded., Intervention: A laparoscopic unilateral ovariectomy was performed to obtain ovarian cortical tissue for cryopreservation. One tissue fragment per participant was used to determine the number of follicles per ovary by serial sectioning and staining. Chromosome analysis was performed on lymphocytes and buccal cells. A blood sample was taken before the ovariectomy for hormonal analysis., Main Outcome Measures: The presence of follicles in ovarian cortex tissue from girls with TS in relation to karyotype, puberty status, and hormonal data., Results: A unilateral ovariectomy was performed on 93 girls with TS. Complications after surgery occurred in 5 girls, including luxation of psychological symptoms in 2 girls. In 13 (14%) girls, a 46,XX cell line was found in buccal cells that was absent in lymphocytes. Follicles were observed in 30 (32%) of the 93 girls and were found mainly in girls with a 46,XX cell line in lymphocytes or buccal cells (Phi coefficient = 0.55). Spontaneous onset of puberty (Phi coefficient = 0.59), antimüllerian hormone (AMH; point-biserial correlation [r] = 0.82), inhibin B (r = 0.67), and follicle-stimulating hormone (r = -0.46) levels were also correlated strongly with the presence of follicles. Furthermore, AMH levels had a significant correlation with the number of follicles per ovary (r = 0.66)., Conclusion: Favorable predictive markers for the presence of follicles included either a 46,XX cell line, spontaneous onset of puberty, or a combination of measurable AMH and normal follicle-stimulating hormone levels. Karyotyping of two peripheral cell lines in girls with TS is recommended to reveal hidden mosaicisms. Ovarian tissue cryopreservation should be offered with caution in a research setting to those with a sufficient ovarian reserve, considering the significant loss of follicles after ovarian tissue cryopreservation and autotransplantation. Physicians should pay attention to the mental health of the girls during the whole process., Clinical Trial Registration Number: Trial registration number: NCT03381300- Preservation of Ovarian Cortex Tissue in Girls With Turner Syndrome - Full Text View - ClinicalTrials.gov. Registered on: December 21, 2017. First patient recruited on January 1, 2018., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Turner syndrome is a genetic disorder that occurs in women with partial or complete absence of an X chromosome., Objective: To describe the clinical, laboratory, and genotypic characteristics of patients with Turner syndrome, treated at three health institutions in Medellin., Patients and Method: A retrospective study was carried out. A total of 97 patients with Turner syndrome (< 18 years) confirmed by karyotype between 2011 and 2018 were included. Patients whose karyotype did not meet the specification of the American College of Medical Genetics were excluded. Data on sociodemographic details, nutritional variables, phenotypic characteristics, and laboratory tests were collected. A descriptive analysis was performed in SPSS software version 20., Results: Median age at diagnosis was 8.5 years (IQR 4-12). The main clinical characteristic was short stature (90%). Additionally, they presented cardiovascular malformations (35%), renal alterations (26%), hearing disorders, mainly hypoacusis (33%), and neuropsychiatric disorders (44%). The most frequent karyotype was 45,X (51%) followed by 45,X/46,XX (14%). The patients with 45,X karyotype had the most classic clinical characteristics. Patients > 5 years old had a higher proportion of weight excess than the general population. Dyslipidemia was found in 62% and hypothyroidism in 22%. 70% of patients > 11 years received pubertal induction; 23% presented spontaneous puberty and 44% of them required hormonal maintenance. 86% received somatropin., Conclusion: The patients with Turner syndrome in our study presented a high frequency of short stature and cardiovascular, renal, hearing, endocrine, and neuropsychiatric comorbidities. The diagnosis was delayed due to the lack of clinical suspicion given its variable presentation.

Objective: To retrospectively analyze sex chromosomal abnormalities and clinical manifestations of children with disorders of sex development (DSD)., Methods: A total of 14 857 children with clinical features of DSD including short stature, cryptorchidism, hypospadia, buried penis and developmental delay were recruited from Zhengzhou Children's Hospital from January 2013 to March 2022. Fluorescence in situ hybridization (FISH) and chromosomal karyotyping were carried out for such children., Results: In total 423 children were found to harbor sex chromosome abnormalities, which has yielded a detection rate of 2.85%. There were 327 cases (77.30%) with Turner syndrome and a 45,X karyotype or its mosaicism. Among these, 325 were females with short stature as the main clinical manifestation, 2 were males with short stature, cryptorchidism and hypospadia as the main manifestations. Sixty-two children (14.66%) had a 47,XXY karyotype or its mosaicism, and showed characteristics of Klinefelter syndrome (KS) including cryptorchidism, buried penis and hypospadia. Nineteen cases (4.49%) had sex chromosome mosaicisms (XO/XY), which included 11 females with short stature, 8 males with hypospadia, and 6 cases with cryptorchidism, buried penis, testicular torsion and hypospadia. The remainder 15 cases (3.55%) included 9 children with a XYY karyotype or mosaicisms, with main clinical manifestations including cryptorchidisms and hypospadia, 4 children with a 47,XXX karyotype and clinical manifestations including short stature and labial adhesion, 1 child with a 46,XX/46,XY karyotype and clinical manifestations including micropenis, hypospadia, syndactyly and polydactyly, and 1 case with XXXX syndrome and clinical manifestations including growth retardation., Conclusion: Among children with DSD due to sex chromosomal abnormalities, sex chromosome characteristics consistent with Turner syndrome was most common, among which mosaicism (XO/XX) was the commonest. In terms of clinical manifestations, the females mainly featured short stature, while males mainly featured external genital abnormalities. Early diagnosis and treatment are particularly important for improving the quality of life in such children.

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., (© 2022. The Author(s).)

Introduction: Turner syndrome association with multi-organ system comorbidities highlights the need for effective implementation of follow-up guidelines. We aimed to assess the adequacy of care with international guidelines published in 2007 and 2017 and to describe the phenotype of patients., Methods: In this multicenter retrospective descriptive cohort study, we collected growth and pubertal parameters, associated comorbidities, treatment, and karyotype in patients diagnosed at age <18 years between 1993 and 2022. We assessed age-appropriate recommendation follow-up (children, adolescents and adults) according to the 2007 guidelines if the last visit was before 2017 (18 recommendations) and the 2017 guidelines if the last visit was after 2017 (19 recommendations)., Results: We included 68 patients followed at Lausanne University Hospital (n=64) and at Neuchatel Regional Hospital (RHNe) (n=4). 2.9% of patients underwent all recommended investigations.Overall, 68.9 ± 22.5% and 78.5 ± 20.6% of the recommendations were followed, before and after 2017 respectively. High implementation rates were found for height, weight and BMI (100%), cardiac (80 to 100%) and renal (90 to 100%) imaging. Low implementation rates were found for Ear, Nose and Throat (ENT) (56.5%), skin (38.5%), dental (23.1%), ophthalmological (10%) and cholestasis (0 to 29%) assessments, depending on age and time of visit. In adults (n=33), the mean proportion of followed recommendations was lower before than after 2017: 63.5 ± 25.8% vs. 78.7 ± 23.4%, p=0.039., Conclusion: Growth parameters, cardiac and renal imaging are well followed. However, efforts should be made for dental, ENT, ophthalmological, skin and cholestasis assessments. Adequacy of follow-up improved with the quality of transition to adult care., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lam, Stoppa-Vaucher, Antoniou, Bouthors, Ruiz, Sekarski, Rutz, Fries, Binz, Bütschi, Vulliemoz, Gawlik, Pitteloud, Hauschild and Busiah.)

Aims: Knowledge on the spectrum of thyroid disorders amongst Turner syndrome (TS) patients in Southeast Asia is limited. This study aimed to evaluate the prevalence of thyroid autoimmunity, the spectrum of autoimmune thyroid disease and association with age and karyotype amongst Malaysian TS girls., Methods: A cross-sectional study was conducted at 11 paediatric endocrine units in Malaysia. Blood samples for antithyroglobulin antibodies, antithyroid peroxidase antibodies and thyroid function test were obtained. In patients with pre-existing thyroid disease, information on clinical and biochemical thyroid status was obtained from medical records., Results: Ninety-seven TS patients with a mean age of 13.4 ± 4.8 years were recruited. Thyroid autoimmunity was found in 43.8% of TS patients. Nineteen per cent of those with thyroid autoimmunity had autoimmune thyroid disease (Hashimoto thyroiditis in 7.3% and hyperthyroidism in 1% of total population). Patients with isochromosome X and patients with 45,X mosaicism or other X chromosomal abnormalities were more prone to have thyroid autoimmunity compared to those with 45,X karyotype (OR 5.09, 95% CI 1.54-16.88, P = 0.008 and OR 3.41, 95% CI 1.32-8.82, P = 0.01 respectively). The prevalence of thyroid autoimmunity increased with age (33.3% for age 0-9.9 years; 46.8% for age 10-19.9 years and 57.1% age for 20-29.9 years) with autoimmune thyroid disease detected in 14.3% during adulthood., Conclusion: Thyroid autoimmunity was significantly associated with the non 45,X karyotype group, particularly isochromosome X. Annual screening of thyroid function should be carried out upon diagnosis of TS until adulthood with more frequent monitoring recommended in the presence of thyroid autoimmunity., (© 2023 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Introduction: Patients with Turner syndrome who harbor Y chromosome material are known to be at increased risk of developing germ cell neoplasms. The optimal timing to perform gonadectomy to reduce the risk of cancer development in these patients is not well defined. We present outcomes of Turner with a Y component (TSY) patients who underwent gonadectomy at our institution., Hypothesis/objective: We hypothesized that tumors could occur in a significant portion of TSY patients at any age and gonadectomy can be safely performed at diagnosis rather than deferred., Study Design: We performed an IRB-approved retrospective single center study in which we queried our institutions electronic health record to identify all patients with TSY who underwent gonadectomy at our institution from 2012 to 2021., Results: In our series of 18 consecutive TSY patients, a tumor was identified in 6 patients (33.3%): 4 (22.2%) with dysgerminoma (DG) [Fig. 1] and 2 (11.1%) with gonadoblastoma (GB)., Discussion: Our cohort of 18 consecutive TSY who underwent gonadectomy over a 9-year period is the largest published single site cohort to date. Additionally, our patient who was found to have GB at 40 days is to our knowledge the youngest TSY patient to be diagnosed with GB in the literature. This patient's remarkably early incidence of tumor occurrence illustrates the urgency of protective gonadectomy. Given the high incidence of tumor formation in this population and the minimal morbidity associated with gonadectomy, we do not recommend delaying gonadectomy in this population for any reason. Our study is vulnerable to selection bias and confounding innate to any retrospective study. There was variation with respect to the frequency and timing of pre-operative imaging as a strict preoperative imaging protocol with sequential studies was not in place at our institution. Additionally, we do not have a comparison cohort of patients who are being followed without operative intervention as all TSY patients at our institution have undergone gonadectomy., Conclusion: TSY patients cannot be safely observed for tumor formation based on clinical factors such as imaging or age. Gonadectomy is safe with a low complication rate and without tumor recurrence during three-year follow-up. We continue to recommend bilateral gonadectomy in this patient population at the time of diagnosis., (Copyright © 2022 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

The authors present the case of a young woman with mosaic karyotype Turner's syndrome who was admitted to a partial hospitalization program due to comorbid schizophrenia. Psychiatric history of the patient included the diagnosis of mild mental retardation and an outpatient appointment due to depressive symptoms. Medical history included hormone replacement therapy due to primary ovarian insufficiency and autoimmune thyroiditis as well as a single case of physical polytrauma due to a road traffic accident years before her admission. On admission, the physical characteristics of Turner's syndrome, chronic phonemic hallucinations and paranoid delusion were found with secondary anger management and social adjustment problems. Brain imaging revealed global cerebral atrophy and a clinically not significant frontal meningioma. Neuropsychological tests confirmed the mild mental retardation and an imbalanced intelligence profile with better verbal than non-verbal functioning. Medication therapy was initiated with social skill training and outpatient follow-ups. Ten months after the initial admission, the antipsychotic monotherapy resulted in a good therapeutic response without a full remission of symptoms. We present our case in the context of a literature review. Orv Hetil. 2023; 164(19): 753-757.

Diagnosis and management of individuals who have differences of sex development (DSD) due to numerical or structural variations of sex chromosomes (NSVSC) remains challenging. Girls who have Turner syndrome (45X) may present with varying phenotypic features, from classical/severe to minor, and some remain undiagnosed. Boys and girls who have 45,X/46,XY chromosomal mosaicism may have Turner syndrome-like features and short stature; therefore, unexplained short stature during childhood requires karyotype analysis in both sexes, particularly if characteristic features or atypical genitalia are present. Many individuals with Klinefelter syndrome (47XXY) remain undiagnosed or are only diagnosed as adults due to fertility problems. Newborn screening by heel prick tests could potentially identify sex chromosome variations but would have ethical and financial implications, and in-depth cost-benefit analyses are needed before nationwide screening can be introduced. Most individuals who have NSVSC have lifelong co-morbidities and healthcare should be holistic, personalized and centralized, with a focus on information, psychosocial support and shared decision-making. Fertility potential should be assessed individually and discussed at an appropriate age. Oocyte or ovarian tissue cryopreservation is possible in some women who have Turner syndrome and live births have been reported following assisted reproductive technology (ART). Testicular sperm cell extraction (TESE) is possible in some men who have 45,X/46,XY mosaicism, but there is no established protocol and no reported fathering of children. Some men with Klinefelter syndrome can now father a child following TESE and ART, with multiple reports of healthy live births. Children who have NSVSC, their parents and DSD team members need to address possibilities and ethical questions relating to potential fertility preservation, with guidelines and international studies still needed., Competing Interests: CG has received honoraria from Merck and Novo Nordisk. EK is an employee of Merck KGaA, Darmstadt, Germany and holds shares in the company. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945). The funder had the following involvement with the study: Merck Healthcare KGaA was involved in organizing and selecting speakers for the meeting that formed the basis for this report, and the authors (except EK) were speakers at the meeting. Merck Healthcare KGaA was involved in the conceptualization of the publication and the decision to publish. There was no commercial influence on analysis or interpretation of any of the information described in the manuscript., (Copyright © 2023 Juul, Gravholt, De Vos, Koledova and Cools.)

Turners' syndrome, although common, is a complex syndrome that requires a multidisciplinary team to manage it. If undiagnosed prenatally or in childhood, Turners' syndrome females often present later to gynaecologists with premature ovarian insufficiency or infertility as their primary presenting complaint. Timely diagnosis and management are key to improving health outcomes in women with Turners' syndrome, as it is associated with multiple comorbidities which left untreated will result in excess morbidity and mortality. We hereby present a case of a 20-year-old female diagnosed to have Turner's syndrome with mosaicism of the X chromosome to highlight the wide array of clinical presentations it can have., Keywords: case reports; infertility; sex chromosome aberrations; Turner syndrome.

Objectives: Early diagnosis in Turner syndrome is desirable to optimize growth and puberty and yet, it is often made late. Here, we aim to identify age at diagnosis, clinical features at presentation and potential strategies to improve the care of TS girls., Methods: Retrospective study, including patients from 14 care centers across Tunisia including neonatal and pediatric care units, adult endocrinology and genetics departments., Results: We identified 175 patients with TS, karyotype showing 45, xmonosomy in 83(47.4 %) with mosaicism in 37(20 %). Mean ± SD, median (range) age at diagnosis available in 173 patients was 13 ± 9.2,12 (birth-48) years. The diagnosis was antenatal in 4(2.3 %), from birth-2 years in 14 (8 %)with lymphoedema (8)and dysmorphic features (9),2-12 years in 53 (35.5 %) including 35 with short stature, 13-18 years in 43(28.8 %) with short stature(28) and delayed puberty(14) and 35(23.5 %) after 18 years, related to ovarian insufficiency (20) and short stature (11). The associated malformations were cardiac in 14 (12.8 %), renal in 22 (19.6 %). A total of 56 girls (32 %) had proven gonadal dysgenesis and 13 (7 %) had otological problems. Parental height was available in 71 girls (40 %) of whom 59 were below the lower end of parental target range (LTR) (83 %)., Conclusions: This first Tunisian multicenter study, the first African of its kind, reveals that more than half of Turner syndrome cases are diagnosed after the age of 12 years. Subsequently, national strategies for an earlier TS diagnosis are needed such as measuring and plotting parental heights as well as introducing a systematic height screening at 5 years in Tunisia with a view to carrying out a re-audit in five years' time., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Turner syndrome (TS) is a chromosomal disorder that affects 25-50 per 100,000 live born females. Patients with TS face a heavy burden of cardiovascular disease (congenital and acquired) with an increased risk of mortality and morbidity compared to the general population. Cardiovascular diseases are a major cause of death in females with TS. Approximately 50% of TS patients have a congenital heart abnormality, with a high incidence of bicuspid aortic valve, coarctation of the aorta and generalised arteriopathy. Frequently, females with TS have systemic hypertension, which is also a risk factor for progressive cardiac dysfunction and aortopathy. This paper aims to provide an overview of the cardiovascular assessment, management and follow up strategies in this high-risk population., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Clinical practice guidelines for individuals with Turner syndrome (TS) recommend screening for neuropsychological concerns (NC) and mental health concerns (MHC). However, current provider screening and referral patterns for NC and MHC are not well characterized. Additionally, prevalence of and risk factors for NC and MHC vary across studies. This multicenter chart review study examined the prevalence, risk factors for, and management of NC and MHC in a cohort of 631 patients with TS from three pediatric academic medical centers. NC and/or MHC were documented for 48.2% of patients. Neuropsychological evaluation recommendations were documented for 33.9% of patients; 65.4% of the sample subsequently completed these evaluations. Mental health care recommendations were documented in 35.0% of records; subsequent documentation indicated that 69.7% of these patients received such services. Most notably, rates of documented MHC, NC, and related referrals differed significantly by site, suggesting the need for standardized screening and referral practices. TS diagnosis in early childhood was associated with an increased risk of NC. Spontaneous menarche was associated with increased risk of MHC. Younger age at growth hormone initiation was associated with both increased risk of isolated NC and co-occurring NC and MHC. Mosaic karyotype was associated with decreased risk of NC and MHC., (© 2023 Wiley Periodicals LLC.)

Background: Retinopathy of prematurity (ROP) and familial exudative vitreoretinopathy (FEVR) are two distinct pathologies of retinal angiogenesis with overlapping clinical features., Methods: Examination, multimodal imaging, and genetic testing were used to guide diagnosis and treatment., Results: We report a combined phenotype of X-linked FEVR and ROP in a 4-month-old girl with mosaic Turner syndrome with ring X chromosome born at 26 weeks gestational age. She was initially diagnosed with atypical ROP with a vitreous band causing a localized traction retinal detachment, inferotemporal to the macula in the right eye, vessels to posterior zone 2 with no clear ridge temporally in the left eye, and fluorescein leakage in both eyes. Due to the suspicion of concurrent FEVR, genetic testing using a vitreoretinopathy panel was performed which revealed a mosaic Turner syndrome associated with 45,X/46,X,r(X), subsequently confirmed by chromosome analysis. The deleted region in the ring X chromosome included the NDP and RS1 genes. The patient was treated with laser photocoagulation of the peripheral avascular retina and sub-Tenon's triamcinolone injection in both eyes, intravitreal injection of bevacizumab in the left eye, and pars plicata vitrectomy in the right eye., Conclusions: In premature neonates with atypical ROP, a clinical suspicion of concurrent FEVR or similar vasculopathy is important and genetic testing may elucidate a genetic etiology, which could influence management and prognosis. Turner syndrome can be connected with co-occurring Mendelian gene disorders, particularly in individuals with mosaicism. The concurrence of FEVR and ROP appears to result in atypical and possibly more severe phenotypes.

Objective: To explore the genetic characteristics of idic(X)(p11.22) in Turner syndrome (TS)., Methods: Two fetuses suspected for sex chromosome abnormalities or ultrasound abnormalities were selected from Chengdu Women's and Children's Central Hospital in October 2020 and June 2020, and amniotic fluid samples were collected for G-banded chromosomal karyotyping analysis, chromosomal microarray analysis (CMA), and fluorescence in situ hybridization (FISH)., Results: The two fetuses were respectively found to have a karyotype of 45,X[47]/46,X,psu idic(X)(p11.2)[53] and 46,X,psu idic(X)(p11.2). CMA found that both had deletions in the Xp22.33p11.22 region and duplications in the p11.22q28 region. FISH showed that the centromeres in both fetuses had located on an isochromosome., Conclusion: The combination of karyotyping analysis, FISH, and CMA is useful for the delineation of complex structural chromosomal aberrations. High-resolution CMA can accurately identify chromosomal breakpoints, which can provide a clue for elucidating the mechanism of chromosomal breakage and rearrangement.

Turner syndrome (TS), a common chromosomal abnormality affecting females, is associated with partial or complete loss of the second sex chromosome. Although the classic karyotype is 45, X, the detection of mosaic TS is increasing. TS is a multi-system disorder with significant endocrine, cardiovascular and reproductive impacts. Accelerated ovarian follicular loss leads to primary amenorrhoea or premature ovarian insufficiency and infertility. Early diagnosis and counselling regarding hormone replacement therapy and future reproductive capacity, including fertility preservation, are essential to improve reproductive outcomes. Pubertal induction or estrogen replacement is usually required to optimise long-term health outcomes; however, initiation may be delayed due to delayed diagnosis. Spontaneous pregnancy occurs in a small number of women; however, many require donor oocytes and assisted reproductive technology to achieve a pregnancy. Pregnancy is a high risk especially when associated with congenital heart disease. Prepregnancy counselling by the multidisciplinary team (MDT) to identify contraindications and optimise pre-existing health issues is essential. Pregnancy management should be led by a maternal-fetal medicine unit with input from the MDT. This review examines reproductive health outcomes in women with TS and how best to manage them to reduce health risks and improve maternal and neonatal outcomes., (© 2022 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.)

Objective: We aimed to investigate how the presence of fetal anomalies and different X chromosome variants influences Cell-free DNA (cfDNA) screening results for monosomy X., Methods: From a multicenter retrospective survey on 673 pregnancies with prenatally suspected or confirmed Turner syndrome, we analyzed the subgroup for which prenatal cfDNA screening and karyotype results were available. A cfDNA screening result was defined as true positive (TP) when confirmatory testing showed 45,X or an X-chromosome variant., Results: We had cfDNA results, karyotype, and phenotype data for 55 pregnancies. cfDNA results were high risk for monosomy X in 48/55, of which 23 were TP and 25 were false positive (FP). 32/48 high-risk cfDNA cases did not show fetal anomalies. Of these, 7 were TP. All were X-chromosome variants. All 16 fetuses with high-risk cfDNA result and ultrasound anomalies were TP. Of fetuses with abnormalities, those with 45,X more often had fetal hydrops/cystic hygroma, whereas those with "variant" karyotypes had different anomalies., Conclusion: Both, 45,X or X-chromosome variants can be detected after a high-risk cfDNA result for monosomy X. When there are fetal anomalies, the result is more likely a TP. In the absence of fetal anomalies, it is most often an FP or X-chromosome variant., (© 2023 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.)

Turner syndrome (TS) is a condition in females missing the second sex chromosome (45,X) or parts thereof. It is considered a rare genetic condition and is associated with a wide range of clinical stigmata, such as short stature, ovarian dysgenesis, delayed puberty and infertility, congenital malformations, endocrine disorders, including a range of autoimmune conditions and type 2 diabetes, and neurocognitive deficits. Morbidity and mortality are clearly increased compared with the general population and the average age at diagnosis is quite delayed. During recent years it has become clear that a multidisciplinary approach is necessary toward the patient with TS. A number of clinical advances has been implemented, and these are reviewed. Our understanding of the genomic architecture of TS is advancing rapidly, and these latest developments are reviewed and discussed. Several candidate genes, genomic pathways and mechanisms, including an altered transcriptome and epigenome, are also presented., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Women with Turner syndrome (TS) are at increased risk of aortic dissection, which is a life-threatening event associated with aortic dilation. Knowledge on the development of aortic dilation over time remains limited. This study aims to describe the prevalence of aortic dilation, to find associated factors and to study aortic growth in women with TS., Methods: In this prospective multicentre cohort study, consecutive adult women with genetically proven TS included between 2014 and 2016 underwent ECG-triggered multiphase CT angiography at baseline and after 3 years. Aortic diameters were measured at seven levels of the thoracic aorta using double oblique reconstruction and indexed for body surface area. Ascending aortic dilation was defined as an aortic size index >20 mm/m 2 . Aorta-related and cardiovascular events were collected. Statistical analysis included linear and logistic regression and linear mixed effects models., Results: The cohort consisted of 89 women with a median age of 34 years (IQR: 24-44). Ascending aortic dilation was found in 38.2% at baseline. At baseline, age (OR: 1.08 (95% CI 1.03 to 1.13), p<0.001), presence of bicuspid aortic valve (BAV) (OR: 7.09 (95% CI 2.22 to 25.9), p=0.002) and systolic blood pressure (OR: 1.06 (95% CI 1.02 to 1.11), p=0.004) were independently associated with ascending aortic dilation. During a median follow-up of 3.0 (2.4-3.6) years (n=77), significant aortic growth was found only at the sinotubular junction (0.20±1.92 mm, p=0.021). No aortic dissection occurred, one patient underwent aortic surgery and one woman died., Conclusions: In women with TS, ascending aortic dilation is common and associated with age, BAV and systolic blood pressure. Aortic diameters were stable during a 3-year follow-up, apart from a significant yet not clinically relevant increase at the sinotubular junction, which may suggest a more benign course of progression than previously reported., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)