X Syndrome Research Articles

Commentary to histologic analysis of gonadal tissue in patients with turner syndrome and Y chromosome material

Commentary to histologic analysis of gonadal tissue in patients with turner syndrome and Y chromosome material

Lifelong medical challenges and immunogenetics of Turner syndrome.

Turner syndrome (TS) is a female phenotypic condition characterized by one or more typical clinical features and the partial or complete absence of a second X chromosome as determined by karyotype analysis. TS, among the most common chromosomal abnormalities, has an estimated prevalence of approximately 1 in 2,500 live-born females, with ethnic and racial differences. TS encompasses a wide array of medical challenges, including cardiovascular, endocrine, autoimmune, and mental health issues, as well as a heightened cancer risk. The somatic stigmata of TS are thought to arise from haploinsufficiency of the X chromosomes. This review explores the lifelong medical challenges and immunogenetics of individuals with TS and aimed to investigate strategies for preventing and managing TS while considering the implications of immunogenetics.

Effects of growth hormone and sex steroid therapy on brain structure and pituitary function in turner syndrome

Introduction: Turner syndrome (TS) is a chromosomal disorder affecting approximately 1 in 2,500 live female births, characterized by the partial or complete absence of one X chromosome. This genetic anomaly leads to physical, cognitive, and endocrine abnormalities, including short stature, gonadal dysgenesis, and structural brain anomalies. Cognitive deficits in TS involve visuospatial processing, memory, and executive function, often linked to structural brain changes. Magnetic resonance imaging (MRI) has revealed significant alterations in gray and white matter volumes in various brain regions. Growth hormone (GH) and sex steroid therapies, such as estrogen and progesterone, are used to address growth and developmental delays in TS. However, their impact on brain structure and pituitary function remains an area of active research. Aim of the Review: To systematically review and synthesize findings on the effects of GH and sex steroid therapy on brain structure and pituitary function in patients with Turner syndrome. Methods: A comprehensive literature review was conducted to identify studies examining the effects of GH and sex steroid therapy on brain structure and pituitary function in TS. Data from various sources were compiled, focusing on MRI-based structural brain changes. Key parameters analyzed included sample size, findings from MRI and fMRI studies, and clinical associations. Studies were summarized and presented in a structured table format. Results: Estrogen-progesterone treatment was found to suppress pituitary gonadotropin release more effectively than estrogen alone, indicating a feedback interaction between pituitary gonadotropin release and sex steroids. MRI studies showed that TS patients exhibit smaller volumes in the hippocampus, caudate, lenticular, thalamic nuclei, and parieto-occipital brain matter, correlating with cognitive deficits. GH-IGF axis abnormalities are modulated by body composition and physical fitness, with sex hormone replacement normalizing the GH-IGF axis and improving body composition. Although GH therapy alone did not significantly improve cognitive functions, the combination of GH with oxandrolone improved working memory. Estrogen deficiency and TS are associated with slower growth in parieto-occipital regions and enhanced volume growth in basal ganglia and cerebellar areas during adolescence, underscoring the importance of estrogen replacement in brain development. Discussion: GH and sex steroid therapies significantly impact brain structure, pituitary function, and clinical outcomes in TS. GH therapy, often combined with sex steroids, improves growth and cognitive functions, particularly working memory. However, GH alone does not significantly impact overall cognitive function. The timing and combination of these therapies are crucial for optimizing outcomes. Regular monitoring and individualized treatment plans are essential to address the complex needs of TS patients. Further research is needed to explore the long-term impacts of these therapies and develop optimal treatment regimens. Conclusion: GH and sex steroid therapies are vital in managing TS contributing to improved growth, body composition, and cognitive enhancements. A multifaceted therapeutic approach and regular monitoring are crucial for optimizing treatment outcomes and quality of life for TS patients.

Prenatal diagnosis and genetic analysis of small supernumerary marker chromosomes in the eastern chinese han population: A retrospective study of 36 cases.

Small supernumerary marker chromosomes (sSMCs) are additional chromosomes with unclear structures and origins, and their correlations with clinical fetal phenotypes remain incompletely understood, which reduces the accuracy of genetic counseling. We conducted a retrospective analysis of a cohort of 36 cases of sSMCs diagnosed in our center. We performed G-banding and chromosomal microarray analysis (CMA). The resulting karyotypes were compared with case reports in the literature and various databases including OMIM, DECIPHER, ClinVar, ClinGen, ISCA, DGV, and PubMed. Karyotype analysis data revealed that 19 out of 36 fetuses were mosaic. Copy number variants (CNVs) analysis results showed that 27 out of 36 fetuses harbored pathogenic/likely pathogenic variants. Among these 27 cases, 11 fetuses carried sex chromosome-related CNVs, including 4 female cases exhibiting Turner syndrome phenotypes and 7 cases showing Y chromosome deletions. In the remaining 16 fetuses with autosomal CNVs, 9 fetuses carried variants associated with Cat eye syndrome, Emanuel syndrome, Tetrasomy 18p, and 15q11-q13 duplication syndrome. Among these, 22 fetuses were terminated, and the remaining 5 fetuses were delivered and developed normally. Additionally, we identified a few variants with unclear pathogenicity. Cytogenetic analysis is essential for identifying the pathogenicity of sSMCs and increasing the accuracy of genetic counseling.

Prevalence, diagnostic features, and medical outcomes of females with Turner syndrome with a trisomy X cell line (45,X/47,XXX): Results from the InsighTS Registry.

Turner syndrome (TS) is defined by partial or complete absence of a sex chromosome. Little is known about the phenotype of individuals with TS mosaic with trisomy X (45,X/47,XXX or 45,X/46,XX/47,XXX) (~3% of TS). We compared the diagnostic, perinatal, medical, and neurodevelopmental comorbidities of mosaic 45,X/47,XXX (n = 35, 9.4%) with nonmosaic 45,X (n = 142) and mosaic 45,X/46,XX (n = 66). Females with 45,X/47,XXX had fewer neonatal concerns and lower prevalence of several TS-related diagnoses compared with 45,X; however the prevalence of neurodevelopmental and psychiatric diagnoses were not different. Compared to females with 45,X/46,XX, the 45,X/47,XXX group was significantly more likely to have structural renal anomalies (18% vs. 3%; p = 0.03). They were twice as likely to have congenital heart disease (32% vs. 15%, p = 0.08) and less likely to experience spontaneous menarche (46% vs. 75% of those over age 10, p = 0.06), although not statistically significant. Congenital anomalies, hypertension, and hearing loss were primarily attributable to a higher proportion of 45,X cells, while preserved ovarian function was most associated with a higher proportion of 46,XX cells. In this large TS cohort, 45,X/47,XXX was more common than previously reported, individuals were phenotypically less affected than those with 45,X, but did have trends for several more TS-related diagnoses than individuals with 45,X/46,XX.

Rare Turner syndrome and lupus coexistence with insights from DNA methylation patterns

Systemic lupus erythematosus (SLE or lupus) is a complex autoimmune disease that can affect multiple organs. While the exact disease etiology remains incompletely understood, there is a suggested influence of X-chromosome dosage in the pathogenesis of lupus. Here, we report a rare case of a female patient diagnosed with mosaic Turner syndrome and subsequently presenting with juvenile-onset SLE. DNA methylation patterns were analyzed in this patient and compared with age-matched female SLE controls, revealing higher methylation levels in interferon-regulated genes previously shown to be hypomethylated in SLE. These data provide a potential link between a gene-dose effect from the X-chromosome and the lupus-defining epigenotype. We hypothesize that the attenuated demethylation in interferon-regulated genes might provide a protective effect explaining the rarity of SLE in Turner syndrome.

An unusual case of 17-hydroxylase deficiency presenting with short stature

17α-Hydroxylase and 17,20-lyase are enzymes encoded by the CYP17A1 gene and are necessary for the production of cortisol and sex steroids. Females with 17α-hydroxylase deficiency usually present with primary amenorrhea and delayed puberty accompanied by hypertension and electrolyte imbalance. Here, we report the case of a 14-year-old female patient who presented with severe short stature and delayed puberty without any complaint suggestive of 17-hydroxylase enzyme deficiency. Laboratory test results showed low cortisol and dehydroepiandrosterone sulfate (DHEA-S) along with high luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Turner syndrome was excluded after genetic analysis showed a 46,XX karyotype, and 17α-hydroxylase deficiency was diagnosed by detecting a c.1319G>A (p.Arg440His) variation/alternation in the patient's CYP17A1 gene.

Turner Syndrome: An Update Review

Turner syndrome was first described by Oklahoman physician Henri Turner in 1938. This syndrome can occur in females who have an absent X chromosome, either completely or partially. The two primary forms of TS are mosaic and classical. Data from newborn genetic screening and epidemiology in the US, Europe, and Japan suggest that it affects 1% to 3% of live female infants. Webbed neck, swollen hands and feet, shield-shaped chest, low hairline, droopy eyelids, high- arched palate, and elevated elbow carrying angle are among the physical traits associated with TS. Standard karyotyping, which looks at the chromosomes of 30 peripheral cells, can confirm the presence of Turner syndrome. Cardiovascular irregularity, hypogonadotropic hypogonadism, infertility, skeletal abnormalities, and autoimmune illnesses are among the complications associated with TS. The main treatment for TS is growth hormone therapy, with different approaches based on the organ involved.

Cell Cycle Kinetics and Sister Chromatid Exchange in Mosaic Turner Syndrome.

Turner syndrome (TS) is caused by a complete or partial absence of an X or Y chromosome, including chromosomal mosaicism, affecting 1 in 2500 female live births. Sister chromatid exchange (SCE) is used as a sensitive indicator of spontaneous chromosome instability. Cells from mosaic patients constitute useful material for SCE evaluations as they grow under the influence of the same genetic background and endogenous and exogenous factors. We evaluated the proliferation dynamics and SCE frequencies of 45,X and 46,XN cells of 17 mosaic TS patients. In two participants, the 45,X cells exhibited a proliferative disadvantage in relation to 46,XN cells after 72 h of cultivation. The analysis of the mean proliferation index (PI) showed a trend for a significant difference between the 45,X and 46,X+der(X)/der(Y) cell lineages; however, there were no intra-individual differences. On the other hand, mean SCE frequencies showed that 46,X+der(X) had the highest mean value and 46,XX the lowest, with 45,X occupying an intermediate position among the lineages found in at least three participants; moreover, there were intra-individual differences in five patients. Although 46,X+der(X)/der(Y) cell lineages, found in more than 70% of participants, were the most unstable, they had a slightly higher mean PI than the 45,X cell lineages in younger (≤17 years) mosaic TS participants. This suggests that cells with a karyotype distinct from 45,X may increase with time in mosaic TS children and adolescents.

Characterization of Turner Syndrome-associated diabetes mellitus.

Diabetes mellitus (DM) risk factors in Turner Syndrome (TS) may include autoimmunity, obesity, beta-cell dysfunction, genetic predisposition and insulin resistance (IR). Evaluate glucose tolerance and DM risk factors in adults with TS. A single centre study with two phases. To determine the prevalence of DM and to assess diabetes risk markers comparing women with TS with and without impaired glucose tolerance (IGT). Tertiary referral center, University College Hospitals. 106 Women with TS (age range 18-70 years) undergoing annual health surveillance. Participants underwent oral glucose tolerance tests (OGTT), with additional samples for autoimmunity and genetic analysis. Glucose tolerance, insulin, autoimmune and single nucleotide polymorphism (SNP) profile. OGTT screening showed that those without a previous DM diagnosis, 72.7% had normal glucose tolerance, 19.5% had IGT, and 7.6% were newly diagnosed with DM. OGTT identified more cases of DM than HbAc1 sampling alone. Women with IGT or DM were older, with higher body mass index and IR. No association was found between autoimmune markers GAD, IA-2 and ZnT8, risk karyotypes or selected SNPs and DM. In DM cases, GAD positivity was associated with requirement for insulin therapy. The median age of onset of the diagnosis of DM was 36 years (range 11-56). In the spectrum of DM subtypes, TS-associated DM lies between type 1 and type 2 DM with features of both. Key factors include weight and IR. Assessing C-peptide or GAD antibodies may aid future insulin requirement.

P-709 A retrospective cohort study of the stability of ovarian reserve in women with Turner Syndrome (TS) and spontaneous menstruation

Abstract Study question What is the stability of ovarian reserve, as measured by anti-Müllerian hormone (AMH), over time in women with TS and spontaneous menstruation beyond age 16? Summary answer Ovarian reserve, as measured by AMH, is stable over time in adult (>16 years) women with TS and spontaneous menstruation. What is known already TS is associated with gonadal dysgenesis and premature ovarian insufficiency (POI). In a minority of TS women, ovarian function is maintained with ongoing menstruation and the possibility of achieving spontaneous pregnancy. There is uncertainty as to the role of fertility preservation in this population. The 2016 Clinical practice guidelines for the care of girls and women with TS recommend counselling women with TS that their probability to conceive spontaneously decreases rapidly with age. However, the natural history of AMH over time in this sub-population has not been reported. Study design, size, duration Retrospective cohort study of patients attending the TS clinic at University College London Hospital between December 2020 and December 2022. This time interval was chosen to ensure that the entire UCLH TS cohort was screened, even if one year of annual follow-up was missed during COVID-19. Clinical records were reviewed to identify adult patients (>16years old) with spontaneous menstruation at any time and at least one measurement of AMH. Participants/materials, setting, methods To assess the stability of the AMH values, the rate of change was calculated using the formula: ratechangeAMH = (lastAMH-baselineAMH)/(time in months between readings). The distribution of the rate of change in the PCOS and non-PCOS groups was then compared using a non-parametric Mann-Whitney test: a regression analysis was performed with the outcome as the ratechangeAMH and the explanatory variables being baseline AMH and age at baseline AMH. Main results and the role of chance 55 patients were identified, median age 25.9 (range 16 to 41).Their karyotypes were 45X (n = 2) 45X/46XX mosaic (n = 28), 45X/47XXX mosaic (n = 11), and other (n = 14). The number of AMH measurements varied from 1-10 and the longest duration of AMH follow-up was 11 years. A subgroup of 9 patients met diagnostic criteria for PCOS. Median AMH for the 45X/46XX group was 21.25pmol/L (range 0.45-59.36), for the 45X group the median was 1.39pmol/L (range 0.20-2.57), in the 47XXX mosaic group the median was 5.05pmol/L (range 0.70-13.97) and in the other group the median was 9.35pmol/L (0.20-54.40). There was a significantly higher mean AMH, adjusted for age and baseline AMH, in the PCOS group than non PCOS group, mean 26.83 vs 16.23 pmol/L (p < 0.01). Overall, the mean rate of change of AMH was +0.0386pmol/L per month 95%CI [-0.0454, +0.1227] and the median was 0.0000pmol/L per month. In the PCOS group, the mean rate of change was +0.0034 pmol/L per month, median 0.0000pmol/L per month. Regression analyses determined that neither age or baseline AMH had a significant impact on the rate of change. Only one patient in the cohort went onto develop POI during the period of follow up. Limitations, reasons for caution The average age of this cohort at the end of the reported follow up period is 25.9. Ongoing prospective follow up is needed to assess the stability of ovarian reserve into the later part of the typical reproductive window to confirm ongoing stability and assess age reated decline. Wider implications of the findings These findings question the necessity and efficacy of fertility preservation in this subset of TS patients as ovarian reserve is stable over time. Until further data is available, we advocate offering observation with annual AMH masurement rather than immediate recourse to fertility preservation. Trial registration number Not applicable

P-676 Obstetric and perinatal outcomes in women with Turner Syndrome: A systematic review and meta-analysis

Abstract Study question What is the pooled risk of adverse obstetric and neonatal outcomes in pregnancies in women with Turner Syndrome (TS)? Summary answer TS women experience high rates of adverse outcomes. Risks are increased in egg donation pregnancies and multiple pregnancies compared to singleton spontaneous pregnancies. What is known already TS affects 1 in 2,000 live female births. The 2017 ‘Clinical Practice Guidelines for the Care of Girls and Women with Turner Syndrome’ acknowledges women with TS are at increased risk of adverse obstetric and perinatal outcomes. Several retrospective cohort studies reporting obstetric and neonatal outcomes in TS pregnancies have been published in recent years. However, these studies are often limited to a single centre cohort, within one country and thus increasing risk of bias. Overall pooled risk estimates for each outcome have yet to be reported. Study design, size, duration A prospectively registered systematic review and meta-analysis was conducted and reported in line with PRISMA guidelines. Overall pooled rates of each outcome Is reported with 95% confidence interval. Pooled risk ratios comparing spontaneous and egg donation pregnancies are also reported. A comparative meta-analysis reports on dichotomous outcomes using summary risk ratio (RR) with 95%CI and on continuous outcomes using weighted mean difference (WMD) with 95%CI. Publication bias was assessed using the Newcastle-Ottawa Scale. Participants/materials, setting, methods A comprehensive literature search was undertaken. Eligibility screening was conducted by 2 independent reviewers. Studies were limited to English language with no time limit. Case reports were excluded. 30 studies reporting obstetric or perinatal outcomes in pregnancies of women with TS were included in the analysis. Outcome data was extracted and tabulated using a standard proforma. Main results and the role of chance 1724 pregnancies were included. Pooled risks: Obstetric outcomes: caesarean section (62.8%)(95%CI:57-76%), pregnancy-associated hypertensive disorders (21%)(95%CI:13-29%), pre-eclampsia (10%)(95%CI:6-14%),gestational diabetes mellitus (6.0%)(95%CI:4-8%), aortic dissection (1.1%)(95%CI:0-2%), intrahepatic cholestasis of pregnancy (4.6%)(95%CI:0-7%), post-partum haemorrhage (17.9%)(95%CI:-3-37%), and maternal mortality (0.3%)(95%CI:0-1%). Perinatal outcomes: prematurity (14.1%)(95%CI:8-18%), low birthweight (25.1%)(95%CI:12-23%), and perinatal mortality (1.2%)(95%CI:0-1%). Egg-donation pregnancies yield significantly higher rates of: caesarean section (82.8% vs. 55.7%) (RR1.49) (95% CI:1.27-1.76), pregnancy-associated hypertensive disorder (33.0% vs 12.9%: p=0.001), pre-eclampsia (16.9% vs 8.2%: p=0.0023), gestational hypertension (17.9% vs 0.0%: p=0.082), low-birthweight (43.0% vs 1.9%: p<0.001) and preterm birth (17.5% vs 0.0%: p<0.001) than spontaneous pregnancies. Multiple pregnancies resulted in high rates of prematurity (70.0%), low birth-weight (73.3%) and pregnancy-associated hypertensive disorders (60.9%). Limitations, reasons for caution Most studies were retrospective and included cases from many years ago so may not be reflective of current obstetric practice and improved care. Most studies were geographically clustered in Europe and North America. Estimations of risk may therefore not be generalisable to other ethnicities and middle and lower income countries Wider implications of the findings This study quantifies the risk of adverse outcomes in pregnancies in women with TS. Risk is increased further in egg donation pregnancies and strategies should aim to screen and prevent complications, particularly hypertensive disorders of pregnancy. Multiple pregnancy should be avoided through use of single embryo transfer. Trial registration number N/a

P-209 Development and characterization of human uterine myometrium in prenatal stage: insights from a single-cell atlas and three-dimensional imaging

Abstract Study question What’s the timepoint of human uterine myometrial formation and how dose it develop in the prenatal stage. Summary answer This study identified that the myometrium layer initially forms at postconceptional week (PCW) 11, ESR1+, IGFBP5, POSTIN may play pivotal role in myometrial development. What is known already Using immunohistochemistry staining, previous studies observed a faint expression of α-SMA in the outer mesenchyme at approximately 8-9 weeks of gestation and showed the early development of muscular layer in the uterine wall, and the expression of α-SMA becomes more prominent in the uterine corpus and cervix by 18 weeks, suggesting the maturation of smooth muscle cells may commence from 18 weeks of gestation. ESR-1 gene encodes estrogen receptor alpha, which plays a pivotal role in menstruation, pregnancy, and parturition. In adult female myometrium, estrogen performs functions in proliferation before term and contractile at term. Study design, size, duration This is an observational study. To investigate when exactly the smooth-muscle tissue appears during uterine development, we have collected 14 uterine tissue samples from 14 aborted fetuses across seven gestational time points from PCW 8 to PCW 15. Participants/materials, setting, methods Uterus from aborted fetuses from PCW8- PCW15 cover the fusion of Mullerian tube and development of Myometrium. The 10X genomics scRNA-seq and immune labeling were performed. In addition, we have integrated scRNA-seq data from adult uterine tissue for comparison. Main results and the role of chance We provide a single cell atlas of the human developing uterus, and we observed that smooth-muscle cells (SMCs), identified by ACTA2, TAGLN, MYH11, exhibited a significant increase in abundance starting from PCW 11, but weaker signals of SMCs were also detected at earlier stages. Using the iDISCO technique with continuous α-SMA labeling to examine the localization of α-SMA in the uterus between PCW10- PCW12, we observed the entire process of myometrial development in 3-D level. We utilized an oblique section of 3-D reconstruction uterus and extended it to 150 μm. Subsequently, apparent signals became visible in the middle of the uterine wall and the uterine fundus. Collectively, these findings suggest that the anatomical myometrium layer initially forms at PCW 11. We used the CytoTRACE to assess the capacity of differentiation of adult and fetal SMCs, SMCs come from fetus appeal a significant grander potential. Specifically, fetal uterine SMCs showed higher expression of ESR1, IGFBP5, and POSTN, while adult uterine SMCs exhibited higher expression of PDGFRB and IGFBP7. These results suggested ESR1+ SMCs could be the precursor of SMCs and SMCs in fetal uterus could be in a primary state. Limitations, reasons for caution While our study did not capture later stages of development or postnatal changes. Future studies are needed to understand the full spectrum of myometrial development. It is also important to note that the findings in this study are specific to human and may not directly translate to other species. Wider implications of the findings Our study provides a basis for studying abnormal myometrial development and its association with various reproductive disorders, such as the abnormal uterine development in female fetus with Turner syndrome. Potential biomarkers or therapeutic targets for uterine malformations and abnormal uterine contractility may also of research interest. Trial registration number not applicable

O-227 First successful ovary allotransplants to Turner’s syndrome patients requiring immunosuppression

Abstract Study question To determine whether we can safely and successfully transplant an ovary tissue allograft from a non-identical donor to her Turner’s syndrome sister. Summary answer We report the first successful cases (with pregnancy) of ovarian tissue allotransplantation to Turners syndrome women using a safe immunosuppression protocol. What is known already Young women with Turner’s have been unable to have children without the use of donor egg IVF, but many Turner’s women would like to have normal hormonal function and to become pregnant naturally. Frozen ovarian cortex tissue can be successfully auto-transplanted back to women with ovarian failure and result in normal pregnancy and live birth with a success rate of 41-76%. This has never been accomplished between a non-identical donor to her Turner syndrome sister. Added benefits are hormonal function obviates the need for hormone replacement, and pregnancy can occur naturally rather than with donor egg IVF. Study design, size, duration 1.) 20 year-old woman with non-mosaic XO Turner’s, no menses, and AMH (Anti-Mullerian hormone) of 0.015 ng/mL, whose 22 year-old sister had two children, normal menses, and an AMH of 4.97. They were HLA identical but ABO incompatible. 2.) A 21 year-old woman with non-mosaic XO Turner’s, no menses and AMH of 0.015 whose 28 year old sister had 2 children, normal menses, and AMH of 2.92. They were ABO compatible, but one HLA mismatch. Participants/materials, setting, methods The left ovary of the donor was removed and dissected. One third of the cortex was transplanted to the right streak ovary of the recipient and the remaining two-thirds were cryopreserved. The immunosuppression protocol consisted of methylprednisolone the morning of surgery along with anti- thymocyte globulin, and for maintenance, tacrolimus 3 mg orally BID with a target trough of 5-10 ng/mL, azathioprine 100 mg orally, and prednisone only 5 mg po daily. Main results and the role of chance By 168 days post-op the first Turner’s recipient was menstruating and ovulating normally with no sign of rejection. Her AMH began to rise at 168 days from 0.05 to 0.35ng/mL by 223 days, typical for a successful ovary cortical graft, and her FSH varied from 4.5 to 8.5 mIU/mL. By one year her uterus grew from infantile to that of a normal adult and she became spontaneously pregnant 10 months later and delivered a healthy baby. The donor FSH was 6.8 mIU/mL, unchanged from pre-op, she continued menstruating normally, and became spontaneously pregnant with her third child (despite having an IUD in place) by six months post op. The second Turner’s syndrome began menstruating monthly at 4 months post-op, and her AMH rose to 0.25 mg/mL as her FSH dropped to 5.3 mIU/mL. At the time of this writing she is 6.5 months post-op and continues to menstruate and ovulate normally. Limitations, reasons for caution There are only the first two cases and therefore at this stage, the conclusions are only a proof of concept. Wider implications of the findings We have demonstrated successful ovarian tissue transplantation with spontaneous pregnancy to Turner’s syndrome females using a safe immunosuppression protocol. The fact that ABO incompatibility did not cause rejection indicates that an ovary tissue graft can survive on diffusion alone. Furthermore, HLA mismatch does not preclude success with this immunosuppression protocol. Trial registration number not applicable

Maternal cardiovascular morbidity and mortality associated with pregnancy in individuals with Turner syndrome: a committee opinion

In individuals with Turner syndrome, the risk of death from aortic dissection or rupture during pregnancy may be as high as 1%, and it is unclear whether this risk persists during the postpartum period owing to pregnancy-related aortic changes. Turner syndrome is a relative contraindication for pregnancy; however, it is an absolute contraindication for pregnancy in a patient with an aortic size index of >2.5 cm/m2 or an aortic size index of ≥2.0 cm/m2 with a documented cardiac anomaly or other risk factors. This document replaces the 2012 document of the same name.

Histologic analysis of gonadal tissue in patients with Turner syndrome and Y chromosome material

This study investigates gonadal histology in individuals with Turner syndrome assigned female at birth and Y-chromosome material (TS+Y) who underwent prophylactic gonadectomy. Despite case reports suggesting spontaneous menarche and pregnancies in TS+Y, this research reveals the absence of germ cells, indicating low fertility likelihood. Germ cell neoplasia in-situ was present in some patients, emphasizing a non-negligible risk of cancer precursor. As no malignancies were found even in older individuals, the study challenges the immediate need for prophylactic gonadectomy upon TS+Y diagnosis. Limited fertility benefits are suggested, emphasizing the need for further research on optimal timing and criteria for the procedure.

Reply to Editorial Comment on “Turner Syndrome With Y Chromosome and Germ Cells: A Case Report Highlighting the Need to Prioritize Individualized Care”

Reply to Editorial Comment on “Turner Syndrome With Y Chromosome and Germ Cells: A Case Report Highlighting the Need to Prioritize Individualized Care”

Variability in Sex Assignment at Birth and Etiological Diagnosis of Differences of Sex Development: A Ten-Year Institutional Experience from Assam.

Differences of sex development (DSD) also known as disorders of sex development encompass a wide spectrum of conditions with varying clinical presentations across different age groups. This study aims to analyse various aetiologies of DSD in Assam and the variability of sex assignment at birth. This retrospective study included the records of people with DSD presenting to a tertiary centre over 10 years. The age at presentation, sex assignment, gender identity, degree of ambiguity, pertinent hormonal and radiological investigations were noted. Descriptive statistics were used for analysis. The age of presentation varied widely, with peaks during infancy and puberty. The most prevalent DSD type was 46, XY DSD (61.2%), followed by 46, XX DSD (19.7%) and sex chromosome DSD (19.1%). Among people with 46, XY DSD, androgen biosynthesis disorders were dominant, particularly 5-a reductase 2 deficiency (46.7%). Among 46, XX DSDs, the most common subtype was androgen excess disorders (51.7%) comprising 21a-hydroxylase deficiency (48,3%) and 11β-hydroxylase deficiency (3.4%). Turner syndrome was most prevalent among sex chromosome DSD (71.4%) with others being Klinefelter syndrome, 45, XO/46, XY mixed gonadal dysgenesis and 46, XX/46, XY chimerism. The degree of ambiguity was variable depending on the type of DSD and similarly, sex assignment at birth was influenced by the level of ambiguity. The study underscores the significance of comprehensive approaches for DSD diagnosis and management, especially in regions with limited resources. The insights gained from this clinical study offer valuable understanding and aid in addressing the complexities associated with these conditions.

Editorial Comment on “Turner Syndrome With Y Chromosome and Germ Cells: A Case Report Highlighting the Need to Prioritize Individualized Care”

Editorial Comment on “Turner Syndrome With Y Chromosome and Germ Cells: A Case Report Highlighting the Need to Prioritize Individualized Care”

Growth hormone therapy in Turner Syndrome (TS): A focused review on glucose metabolism outcomes

Introduction: Turner Syndrome (TS) patients inherently possess a higher risk of developing glycemic abnormalities due to their unique genetic makeup, and the administration of growth hormone (GH) therapy, while beneficial for growth, might exacerbate this tendency towards disturbed glucose metabolism. Objective of the Review: To evaluate the existing literature on the effects of GH therapy on glucose metabolism in TS patients, highlighting the balance between therapeutic benefits and potential metabolic risks. Methods: This review scrutinizes studies published from 2000 to 2024, focusing on the outcomes related to glucose metabolism in TS individuals undergoing GH therapy, encompassing aspects like insulin sensitivity, glucose tolerance, and metabolic health. Results: Insulin Sensitivity and Resistance: Initial findings suggest that GH therapy may exacerbate insulin resistance and elevate insulin levels, although these effects appear transient and potentially reversible after the cessation of therapy. Long-term Metabolic Outcomes: Later studies indicate that long-term GH therapy may lead to an improvement in insulin sensitivity and a normalization of carbohydrate metabolism, particularly after the therapy is discontinued. Variable Impacts on Glucose Tolerance: The reviewed literature shows mixed effects on glucose tolerance, with some studies reporting no significant changes, while others highlight a potential risk for worsening glucose metabolism. Body Composition and Metabolic Profile: Positive changes in body composition and lipid profiles were noted, which could confer metabolic benefits, yet the therapy's role in increasing insulin levels warrants careful consideration. Individual Variability and Monitoring Needs: The diverse responses to GH therapy underscore the necessity for individualized treatment plans and diligent metabolic monitoring to mitigate potential risks and optimize therapeutic outcomes. Conclusion: The administration of GH therapy in TS requires a delicate balance, considering its potential to both benefit and pose risks to glucose metabolism. Tailored monitoring and a comprehensive understanding of the individual patient’s metabolic response are essential for maximizing the therapy's efficacy while minimizing associated metabolic complications.