RARE DISEASE
Turner syndrome
Turner syndrome
Turner syndrome
Synonyms: 45,X syndrome, 45,X/46,XX syndrome
Synonyms: 45,X syndrome, 45,X/46,XX syndrome
Synonyms: 45,X syndrome, 45,X/46,XX syndrome
Drug discovery
8
drugs
With orphan designations
Overview
Turner syndrome (TS) is a genetic disorder affecting phenotypic females, caused by complete or partial absence of one X chromosome (45,X or mosaic karyotypes). It presents with short stature, ovarian failure, cardiovascular anomalies, and increased risks of autoimmune disorders, osteoporosis, and metabolic conditions. Early diagnosis and multidisciplinary care—including growth hormone therapy, estrogen replacement, and targeted management of comorbidities—are critical to improving outcomes and quality of life [1][3][12][15].
Burden
Mortality: Reduced life expectancy (~10 years shorter) due to cardiovascular complications (e.g., aortic dissection) [4][19].
Morbidity: 40–50% have congenital heart defects; 30–50% develop autoimmune thyroiditis; 50–80% experience sensorineural hearing loss [4][6][15].
Healthcare utilization: 72% hospitalized in the first year of life, with frequent surgeries (e.g., cardiac interventions) and antibiotic use [9][14][19].
Therapies
Growth hormone therapy: Initiated by age 5–6 to improve adult height (average gain: 5–10 cm) [3][13][18].
Estrogen/progesterone replacement: Started around age 11–12 to induce puberty and support bone health [3][8][11].
Multidisciplinary care: Cardiology, endocrinology, and reproductive specialists address congenital heart defects, metabolic risks, and fertility challenges [1][6][10].
Categories: rare circulatory system diseases, rare developmental anomalies during embryogenesis, rare endocrine diseases, rare genetic diseases, rare gynecological and obstetric diseases, rare infertility disorders, rare neurological diseases, rare ophthalmic disorders, rare renal diseases, rare skin diseases, rare transplant-related disorders, rare urogenital diseases
Research Papers
1,198 drug discovery papers about Turner syndrome, with 1 first-in-class and 6 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,198 drug discovery papers about Turner syndrome, with 1 first-in-class and 6 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-08-17 | Pulmonary Hypertension Workup Unraveling a Rare Anomaly in Turner Syndrome.
Turner syndrome (TS) is associated with congenital heart disease, most commonly a bicuspid aortic valve and coarctation of the aorta; however, partial anomalous pulmonary venous return (PAPVR) remains an underrecognized cardiovascular anomaly. PAPVR, in which one or more pulmonary veins drain into the systemic venous circulation, can cause left-to-right shunting, right-sided chamber dilation, and pulmonary hypertension (PH). We report the case of a 51-year-old woman with TS and hypertension who presented with dyspnea and an estimated right ventricular systolic pressure of 55 mmHg on echocardiography. Right heart catheterization (RHC) showed severe PH, with a mean pulmonary artery pressure of 53 mmHg, a pulmonary capillary wedge pressure of 16 mmHg, and a pulmonary vascular resistance of 2.1 Wood units, along with unexpectedly high pulmonary artery oxygen saturations suggestive of a left-to-right shunt. Cardiac MRI demonstrated right-sided enlargement with a pulmonary-to-systemic flow ratio (Qp:Qs) of approximately 3.0 but no intracardiac defect. CT confirmed PAPVR, with the right superior and middle pulmonary veins draining into the superior vena cava and the left superior pulmonary vein draining into the brachiocephalic vein. She improved clinically with tadalafil and furosemide and was referred for surgical evaluation. In patients with TS and unexplained PH, an unexpectedly high pulmonary artery oxygen saturation on RHC should raise suspicion for an occult left-to-right shunt. When no intracardiac defect is identified, multimodality imaging with cardiac MRI and CT can reveal extracardiac shunt lesions such as PAPVR and guide timely referral for definitive management.
2026-06-26 | Transdermal versus oral hormone replacement therapy and bone mass density in Turner syndrome patients: a pilot study.
Women with Turner syndrome (TS) are at increased risk of reduced bone mineral density (BMD) due to primary ovarian insufficiency. This study aimed to assess longitudinal changes in BMD in TS patients receiving oral or transdermal hormone replacement therapy (HRT) and to identify factors associated with bone density decline. This retrospective pilot study included 40 TS patients treated with oral or transdermal estradiol. The median age was 22 years in both the transdermal (20-30) and oral (20-27) groups. Median BMI was 23.1 (21.1-25.5) and 25.4 (22.1-29.1), respectively. Dual-energy X-ray absorptiometry (DEXA) of the lumbar spine and femoral neck was performed at baseline and follow-up. The primary outcome was the t-score at both sites. Univariable and multivariable logistic regression analyses were used to identify factors associated with declining t-scores. At baseline, 38.3% of patients had osteopenia, and 3.3% had osteoporosis. During follow-up, a decline in t-scores at at-least one skeletal site was observed in 47.5% of patients. No significant differences were found between oral and transdermal estradiol therapy regarding absolute t-scores, t-score changes, or the proportion of patients with declining t-scores (all p > 0.05). In multivariable analysis, lower vitamin D levels at follow-up were independently associated with declining t-scores. In TS patients, the route of estradiol administration did not significantly affect long-term BMD outcomes. Despite HRT, a substantial proportion of patients experienced bone loss. Vitamin D status has emerged as the most relevant modifiable factor associated with declining BMD, highlighting the need for bone health management beyond HRT.
2026-05-18 | Integrative Bioinformatics Analyses Reveal X Chromosome Inactivation Escape Genes Dosage Dysregulation Is the Primary Contributor to Turner Syndrome.
Turner syndrome is a rare disorder resulting from abnormalities in the number or structure of a single X chromosome. It stands as the sole survivable monosomy observed in humans. Individuals affected by Turner syndrome commonly face significant complications, including impaired gonadal development, short stature, and intellectual disabilities. Despite extensive research, the complete understanding of the pathogenesis behind Turner syndrome remains elusive. This study aimed to elucidate the molecular mechanisms of Turner syndrome by identifying key X chromosome inactivation escape genes and exploring their potential contributions to genotype-phenotype correlations and therapeutic targets through integrative bioinformatics analyses. The study included three RNA-seq datasets, consisting of 72 patients with Turner syndrome and 58 individuals with normal cytogenetics. Differentially expressed gene analysis, protein-protein interaction network analysis, and functional enrichment analysis were conducted to ascertain hub genes. Furthermore, pivotal lncRNAs and transcription factors were identified through competitive endogenous RNA network analysis and transcription factor enrichment analyses. This study made a significant contribution by exploring the relationship between Turner syndrome genotypes and various phenotypes at the transcriptomic level. We found hub genes associated with hormone regulation, including growth hormone. Moreover, we highlighted 10 crucial X chromosome inactivation escape genes (ASMTL, CD99, DHRSX, EIF1AX, JPX, KDM5C, KDM6A, SLC25A6, XIST, and ZFX), which may serve as core pathogenic factors in Turner Syndrome. Additionally, based on our findings, we proposed certain drugs as potential new therapeutic strategies for Turner Syndrome. Our study provides substantial evidence supporting the correlation between genotype and various phenotypes in Turner Syndrome. Furthermore, we shed light on the potential pathogenic significance of X chromosome inactivation escape genes. These findings open up new possibilities for therapeutic interventions.
2026-04-01 | Thoracic spinal anesthesia for emergency derivative colostomy in a turner syndrome patient
Sir, We read with great interest the recent case report by Guillarducci et al., entitled “Anesthetic implications of elective cesarean section in a parturient with Noonan syndrome and complex cardiomyopathy: A case report,” which highlighted the importance of individualized anesthetic planning and demonstrated that neuraxial anesthesia can represent a safe and effective approach in selected high-risk patients.[1] Notably, Noonan syndrome is characterized by a Turner phenotype, reflecting the shared anatomical and cardiovascular features between these two conditions, which may significantly impact anesthetic management.[1] Turner syndrome (TS) is a genetic disorder caused by sex chromosomal abnormalities affecting women and is associated with a wide spectrum of anatomical and physiological alterations, particularly involving the airway and cardiovascular system.[2] Short webbed neck, maxillary and mandibular hypoplasia, reduced tracheal length, and altered tracheal anatomy may contribute to difficult airway management.[3,4] Additionally, congenital cardiovascular abnormalities and pulmonary arterial hypertension may significantly increase perioperative morbidity and mortality, particularly during general anesthesia.[5] Therefore, thorough understanding of these anatomo-physiological abnormalities is essential to ensure safe anesthetic care. Neuraxial anesthesia may represent a valuable alternative to general anesthesia in selected high-risk patients, allowing avoidance of airway manipulation and reduction of hemodynamic stress.[3,4] However, short stature requires careful individualization of local anesthetic dosing, and spinal deformities such as scoliosis may increase the technical difficulty of neuraxial block placement. We describe the case of a 62-year-old ASA IV woman with TS, who underwent emergency derivative colostomy for intestinal obstruction. The patient presented multiple severe comorbidities, including heart failure with moderate left ventricular dysfunction, moderate precapillary pulmonary arterial hypertension (PAP 65 mmHg), persistent atrial fibrillation on anticoagulation therapy, end-stage renal disease on hemodialysis, chronic obstructive pulmonary disease requiring oxygen therapy, hypothyroidism, neurogenic bladder, chronic iron-deficiency anemia due to colonic angiodysplasia, adrenal adenoma, and previous endometrial carcinoma. After obtaining informed consent, thoracic spinal anesthesia was performed in the sitting position using a 25 G Whitacre needle at the T9–T10 interspace, administering a low dose of bupivacaine 0.25% 8 mg with dexmedetomidine 5 mcg as adjuvant. Minimal sedation with midazolam 1 mg was provided. Hemodynamic stability was maintained using continuous norepinephrine infusion (0.05 µg/kg/min), guided by minimally invasive monitoring. The surgical procedure lasted approximately 70 min. The patient maintained spontaneous breathing and stable vital parameters throughout the operation. No intraoperative or postoperative complications occurred. Postoperative analgesia required only acetaminophen, without opioid administration. This case further supports the concept that neuraxial anesthesia, when carefully individualized, may represent a safe and effective anesthetic strategy in high-risk patients with TS, particularly in those presenting Turner phenotype features associated with increased risks of general anesthesia. Careful patient selection, dose adjustment, and experienced anesthetic management remain essential to optimize perioperative safety in this challenging population. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
2026-03-27 | Semaglutide Plus Low-Dose Metformin Combination Therapy for the Treatment of Obesity and Prediabetes in a Woman with Partial Deletion of the X Chromosome Long Arm.
Background and Clinical Significance: Over the last two decades, glucagon-like peptide-1 (GLP-1) receptor agonists have dramatically improved the management of type 2 diabetes mellitus and obesity. Currently, little is known about the use of semaglutide (a second-generation GLP-1 receptor agonist) in patients with X chromosome abnormalities. Herein, we describe the therapeutic use of semaglutide in a woman with a partial deletion of the X chromosome long arm (partial Xq deletion) and comorbid obesity. We also conducted a narrative mini-review on overweight, obesity and common metabolic derangements in patients with partial Xq deletions and Turner syndrome. Case Presentation: A 65-year-old Italian woman with a partial Xq deletion, class 1 obesity, insulin resistance, prediabetes, hypercholesterolemia and metabolic dysfunction-associated steatotic liver disease (MASLD) was referred to our Institution for persistent difficulty in managing excess body weight despite regular adherence to different structured physical activity programs and hypocaloric diets. Therefore, we prescribed a combination therapy based on low-dose metformin (500 mg/day) and once-weekly subcutaneous semaglutide (as an adjunct to lifestyle intervention). At 5 months after initiation of the combination therapy, blood tests showed metabolic improvements, including improvement of prediabetes (0.3-percentage-point reduction in glycated hemoglobin [HbA1c] values) and normalization of markers of insulin sensitivity and insulin resistance (QUICKI, HOMA-IR and TyG index). At 8 months, the patient showed substantial weight loss, which amounted to 13.8 kg (percent total body weight loss: 20.95%), and was accompanied by a notable reduction in waist circumference (-14.1 cm). Moreover, body mass index (BMI)-based weight status improved from class 1 obesity to overweight: BMI value of 25.1 kg/m2 at 8 months vs. 31.8 kg/m2 at baseline (near-normalization of BMI values). Bioelectrical impedance analysis (BIA) revealed that the patient's overall weight loss consisted of 74.6% fat mass (FM) loss (-10.3 kg) and 25.4% fat-free mass (FFM) loss (-3.5 kg). Despite the expected FFM reduction in absolute terms, percent FFM increased at 8 months (+9.6%). This increase in percent FFM was accompanied by a reduction in percent FM at 8 months (-9.6%), indicating an overall improvement in body composition. Normalization of percent FM and FFM values (28.6% and 71.4%, respectively) was also achieved at 8 months. These body composition changes are in line with those observed in clinical trials investigating the use of semaglutide in patients with overweight or obesity. At 6 months, an abdominal ultrasound also showed the disappearance of the sonographic characteristics suggestive of mild-to-moderate hepatic steatosis. Low-dose metformin (500 mg/day) and subcutaneous semaglutide (up to a weekly dose of 1.7 mg) were well tolerated by the patient. Conclusions: To the best of our knowledge, this is the first case documenting the effective use of once-weekly subcutaneous semaglutide plus low-dose metformin combination therapy for the treatment of obesity and prediabetes in a woman with a partial Xq deletion. Large prospective cohort studies are warranted to better investigate the safety and efficacy profile of semaglutide (alone or in combination with metformin) in patients with numerical and structural X chromosome abnormalities, comorbid overweight/obesity and related metabolic disorders.
gene therapies
2026-07-02 | Influence of X-Chromosome Inactivation in Pathogenesis of Turner Syndrome
Turner syndrome (TS), a disorder caused by the complete or partial absence of an X chromosome, exhibits significant clinical variability that cannot be fully explained by chromosomal anomalies alone. This narrative review highlights the crucial role of epigenetic mechanisms, particularly X-chromosome inactivation (XCI), in shaping the TS phenotype. The haploinsufficiency of genes that normally escape XCI is a primary driver of TS features. The specific epigenetic consequences depend on the chromosomal anomaly. In complete monosomy (45,X), the absence of escape-mediated dosage compensation genes from a second X chromosome amplifies haploinsufficiency across X-linked escape genes. Isochromosome Xq (i(Xq)) variants involve the loss of the short arm (Xp) and duplication of the long arm (Xq), creating a dual dosage imbalance with extreme XCI skewing. Carriers of i(Xq) also have a heightened risk for autoimmune disorders compared to those with 45,X TS. For ring-X chromosomes (r(X)), which are mitotically unstable, the functional status of the XIST gene is critical. If the ring is XIST-negative, it remains transcriptionally active, resulting in functional disomy and a more severe phenotype with pronounced neurodevelopmental and craniofacial features. Ultimately, the clinical heterogeneity in TS arises from a complex interplay of the specific chromosomal structure, tissue-specific mosaicism, XIST function, and variable escape from XCI, defining TS as a disorder of epigenetic and gene-regulatory imbalance. However, future research requires a better understanding of the complex mechanism of X-chromosome inactivation.
2026-05-29 | Sleep Disorders in Klinefelter Syndrome and Other Sex Chromosome Aneuploidies: A Narrative Review.
Sex chromosome aneuploidies (SCAs) are among the most frequent types of chromosomal aneuploidies and include Klinefelter syndrome (47,XXY and higher-grade variants), 47,XYY syndrome, Turner syndrome (45,X), and trisomy X (47,XXX). These conditions share complex neurodevelopmental, endocrine, and metabolic features with important implications for reproductive and general health. Sleep plays a pivotal role in neurocognitive functioning, mood regulation, cardiometabolic homeostasis, and hypothalamic-pituitary-gonadal axis activity, yet sleep disorders remain poorly characterized and under-recognized in SCAs. This narrative review synthesizes current evidence on sleep disturbances in SCAs, with particular emphasis on male phenotypes, while integrating evidence from female SCAs to highlight shared mechanisms and overlapping sleep phenotypes. Available data indicate an increased prevalence of insomnia, sleep fragmentation, excessive daytime sleepiness, circadian rhythm disturbances, and sleep-disordered breathing from childhood through adulthood. In Klinefelter syndrome, sleep alterations appear multifactorial, arising from the interaction between hypogonadism, obesity, psychiatric vulnerability, neurocognitive deficits, and possible circadian and melatonin dysregulation. Evidence in 47,XYY and higher-grade male SCAs, although limited, suggests a predominant contribution of neurodevelopmental and behavioral factors. Emerging findings also implicate oxidative stress as a potential mechanistic link between sleep disruption, metabolic dysregulation, and neurocognitive impairment. Overall, the literature is fragmented and methodologically heterogeneous, underscoring the need for systematic sleep screening and integrated multidisciplinary management within andrological care pathways to improve long-term health and reproductive outcomes in individuals with SCAs.
2026-04-01 | Turner syndrome and acute type A aortic dissection: a national inpatient analysis of risk and outcomes.
Although acute type A aortic dissection (ATAAD) is a recognised complication of Turner syndrome, population-level data describing its prevalence and outcomes remain limited. We queried the National Inpatient Sample (2002-2020) and generated three groups: TS + ATAAD+, TS + ATAAD-, and TS-ATAAD+ in our retrospective observational cohort study. Primary outcomes were ATAAD hospital admission rate and in-hospital mortality; secondary outcomes included length of stay. Sampling weights were applied to all analyses. A total of 51,426 Turner syndrome hospitalisations were identified. Median ages were 40 years (interquartile range 31-50) for TS + ATAAD+ and 32 years (interquartile range 9-49) for TS + ATAAD- (p < 0.001). Overall, 0.27% of Turner syndrome hospitalisations presented with ATAAD. Compared with TS + ATAAD-, those with ATAAD had higher mortality (13.1% vs 2.1%, p < 0.001) and longer length of stay (median 8 vs 3 days, p < 0.05). Rates of bicuspid aortic valve (34.3% vs 3.5%, p < 0.001), hypertension (46.0% vs 25.7%, p < 0.05), and complete heart block (14.6% vs 0.8%, p < 0.001) were also higher. Multivariable analysis showed bicuspid aortic valve (adjusted odds ratio 24.31, 95% CI 8.8-67.3) and age (adjusted odds ratio 1.02, 95% CI 1.01-1.04) predicted ATAAD. Compared with TS-ATAAD+ patients, those withTS + ATAAD+ were younger (40 vs 68 years, p < 0.001), while mortality, length of stay, hypertension, and bleeding rates were similar. ATAAD is highly lethal in patients with and without Turner syndrome. In Turner syndrome, ATAAD is associated with higher mortality, longer hospitalisation, and higher rates of bicuspid valve disease and hypertension.
2026-02-12 | Ultra-performance Liquid Chromatography-mass Spectrometry-based metabolic profiling of prepubertal children with Turner syndrome.
This research aims to characterize the metabolic profiles of prepubertal patients with TS to elucidate the potential impact of X chromosome haploinsufficiency on glycolipid metabolism. Fouty-nine prepuberty TS and 50 age-, sex- and BMI standard deviations scores (SDS)-matched healthy children (HC) were enrolled. Untargeted ultra-performance liquid chromatography-coupled mass spectroscopy was performed in all participants. Differentially expressed metabolites (DEMs) were identified and annotated using the KEGG and HMDB databases. Correlation analyses were conducted to explore associations between DEMs and relevant clinical parameters. Logistic regression models were performed to evaluate the potential impact of the interaction between X-chromosome haploinsufficiency and metabolite abnormalities on metabolic status. Metabolomics analyses indicated separation between TS and HC groups with 70 DEMs enriched in caffeine metabolism, purine metabolism, and insulin resistance pathways. Among TS, 34 DEMs were found to be correlated with height, weight, glucose and lipid metabolism, and sex hormone levels. Three DEMs-sodium cholate, N-arachidonoyl-L-serine, and N1-pyrazin-2-yl-4-chlorobenzamide--were identified to interact with X chromosome haploinsufficiency in influencing metabolic status. Prepubertal children with TS exhibit distinct metabolic profiles, with DEMs enriched in caffeine metabolism, purine metabolism, and insulin resistance pathways. These metabolites show correlations with clinical parameters and demonstrate interactions with X chromosome haploinsufficiency affecting metabolic health. This study described the distinctive metabolic profiles of TS children for the first time. The impact of X chromosome haploinsufficiency on glycolipid metabolism was elucidated through a study of prepubertal TS children. Three novel metabolites were identified with significant interaction effects with X chromosome haploinsufficiency on glycolipid metabolic status.
2025-12-03 | Exercise capacity in girls with Turner syndrome.
Data on exercise capacity of pediatric patients with Turner syndrome (TS) is scarce. This study was aimed at evaluating the cardiopulmonary response to exercise in girls with TS aged 8 to 18 years. In this prospective, single-center case-control cohort study girls with TS were matched to healthy controls based on gender, age, and weight. All girls performed a maximal incremental cardiopulmonary exercise test (CEPT) on an electromagnetically braked cycle ergometer. Key variables measured included peak oxygen uptake (VO2 peak) and maximal workload both expressed as percentages of predicted values based on gender, age, and weight. O2 pulse is expressed in milliliters per heartbeat. Twenty-one girls with TS were included and matched with 21 control patients. Girls with TS demonstrated significantly lower VO2 peak values (% of predicted) compared to controls (mean difference: - 10.3%, p = 0.014). Similarly, maximal workload was significantly reduced in the TS group (mean difference: - 17.6%, p = 0.002). A general linear model confirmed that group status (TS vs. control) was a significant predictor of both VO2 peak and maximal workload, independent of age and weight. No significant differences were observed in maximal heart rate or blood pressure between the two groups. O2 pulse (ml/beat) was significantly lower in patients with TS (7.7 ± 1.2 ml/beat) versus healthy controls (8.6 ± 1.4 ml/beat, p = 0.03).Conclusion: Girls with TS exhibit a reduced exercise capacity compared to their healthy peers, as evidenced by lower VO2 peak, maximal workload and O2 pulse during standardized CPET. Further research on pathophysiology, evolution over time, and impact of targeted interventions is needed.
proteins
2026-06-29 | Model-based somapacitan dosing and IGF-I response in children born SGA or with ISS, Noonan or Turner syndromes.
The weekly insulin-like growth factor I (IGF-I) profile for children and adolescents treated with long-acting growth hormone differs from that of daily growth hormone (GH). The objective of this study is to provide guidance on the use of once-weekly somapacitan and IGF-I monitoring in prepubertal short children and adolescents born small for gestational age (SGA) or with idiopathic short stature (ISS), Noonan syndrome (NS), or Turner syndrome (TS). Modeling, including population pharmacokinetic/pharmacodynamic (PK/PD) modeling, were utilized, analyzing IGF-I data from 4 clinical studies, including 2 phase 3 trials (REAL8: NCT05330325; REAL9: NCT05723835) involving children and adolescents born SGA (N = 80), ISS (N = 69), NS (N = 62), and TS (N = 79), along with additional data from phase 2 (REAL5: NCT03878446, N = 59) and phase 1 trials (NCT01973244, N = 24). Relationships between somapacitan dose, exposure, baseline IGF-I SD score (SDS), and height velocity (HV) were established in children born SGA, with similar responses anticipated for those with ISS, NS, or TS. A linear model enabled the estimation of average weekly IGF-I exposure from a single sample collected during the somapacitan dosing interval. IGF-I SDS simulations support flexible dosing changes while maintaining a minimum of 4 days between doses. Somapacitan 0.24 mg/kg/week produced similar IGF-I SDS changes and height velocity increases as daily GH in prepubertal short children and adolescents born SGA or with ISS, NS, or TS. The results support that the guidance already established for GHD regarding somapacitan initiation, dosing flexibility, and IGF-I monitoring remain appropriate for prepubertal short children and adolescents born SGA or with ISS, NS, or TS.
2026-06-15 | First reported case of Turner syndrome with Krabbe disease in a child: a case report.
Turner syndrome (TS) is a congenital sex chromosome disorder. Krabbe disease (KD) is a rare autosomal recessive neurometabolic disorder. Here, we reported the first case of a child with both conditions. A girl presenting as short stature was diagnosed with 45,X TS at the age of 9 years, showed significant height improvement with recombinant human growth hormone (rhGH) therapy, which was well-tolerated without drug-related adverse events. At age 14 years, she was hospitalized with nausea, abdominal pain, dizziness, fatigue, and weight loss, and was diagnosed with secondary adrenal insufficiency. Comprehensive evaluation ruled out TS and prior rhGH therapy as causes for secondary adrenal insufficiency, prompting consideration of other inherited metabolic disorders. Ultimately, the multidisciplinary team conducted an evaluation confirming KD through genetic testing and detection of below-normal galactocerebrosidase enzyme activity (40.6 nmol/17h/mg protein). Since her height improvement was satisfactory, rhGH therapy was temporarily discontinued. After evaluation, she was deemed ineligible for hematopoietic stem cell transplantation. We initiated hydrocortisone replacement therapy to address her adrenal insufficiency symptoms. Overall, this case highlighted that secondary adrenal insufficiency could serve as an atypical clinical manifestation of KD. Furthermore, rhGH demonstrated satisfactory efficacy and safety in improving short stature in patient with 45,X TS.
2026-06-05 | Growth hormone therapy and near-final height in SHOX deficiency and turner syndrome: a real-world single-center retrospective cohort study.
Short stature homeobox-containing (SHOX)-gene haploinsufficiency causes short stature both in isolated SHOX deficiency and in Turner syndrome (TS), yet head-to-head data on growth-hormone (GH) outcomes remain scarce. We therefore compared growth response and near-final height (NFH) after GH therapy between girls with SHOX deficiency and those with TS. Single-centre retrospective cohort study. In this single-centre retrospective cohort, we reviewed 44 pre-pubertal girls who received daily GH (mean 0.045 mg/kg/day) between 2015 and 2024 and subsequently reached NFH (bone age ≥ 14 y; height velocity < 2 cm/year). Ten had molecularly confirmed SHOX deficiency and 34 had karyotype-proven TS. Baseline auxology, annual height velocity, pubertal timing, treatment duration, NFH standard-deviation score (SDS) and total height SDS gain were analysed. Mean chronological and bone ages at GH initiation were similar (10.7 ± 1.9 vs 10.4 ± 2.7 years). Baseline height SDS was lower in TS (-3.51 ± 1.0) than in SHOX (-2.66 ± 0.8). First-year growth velocity was higher in SHOX (8.55 ± 1.4 cm/year) than TS (6.72 ± 1.9 cm/year; p = 0.01). Puberty began earlier in SHOX (11.6 ± 1.3 years) than TS (13.7 ± 1.5 years; p < 0.01), and GH exposure was shorter (2.00 ± 0.4 vs 4.38 ± 2.3; p < 0.01). Observed NFH-SDS was similar between groups (SHOX - 2.46 ± 1.2 vs TS - 2.47 ± 1.0). Unadjusted height-SDS gain was greater in TS (1.04 ± 0.1 vs 0.20 ± 0.2; p = 0.04). In exploratory ANCOVA models adjusting for baseline age, baseline height SDS, and GH treatment duration, adjusted height-SDS gain did not differ significantly between groups. TS was associated with a greater unadjusted height-SDS gain, whereas SHOX deficiency was characterized by earlier puberty and shorter GH exposure. Although observed NFH-SDS was similar, these findings highlight how differences in pubertal timing and treatment duration may influence growth outcomes in routine clinical practice and should be interpreted as reflecting real-world growth trajectories rather than intrinsic biological responsiveness to GH therapy. • Growth hormone therapy is an established treatment for short stature in both SHOX deficiency and Turner syndrome. • Treatment response is influenced by several factors, including age at treatment initiation and pubertal development. • This study provides a real-world comparison of growth hormone treatment outcomes in girls with SHOX deficiency and Turner syndrome. • Spontaneous pubertal progression in SHOX deficiency versus medically induced puberty in Turner syndrome may substantially influence the duration of the therapeutic growth window and the observed growth response.
2026-04-25 | Final Height in Patients with Turner Syndrome Treated With Growth Hormone Therapy.
Turner syndrome (TS) is the most common sex chromosome abnormality in girls. Short stature is the most distinctive feature. This study aimed to evaluate factors affecting final height (FH) in patients with TS who received growth hormone (GH) therapy and achieved their final height (FH). About 48 patients with TS who received GH therapy and reached their FH were included and examined retrospectively. Initial height, standard deviation score (SDS), FH, and FH SDS measurements of the patients were obtained. Additionally, factors affecting FH were analyzed. Growth hormone was administered at a dose of 45.6 ± 6.2 (min-max: 34-69) μg/kg/day at a mean age of 11.7 ± 2.9 years. The duration of therapy was 4.3 ± 1.4 years. The mean FH of the patients was 147.80 ± 5.98 cm. About 29.2% (n=14) of the patients reached a height above the thirdpercentile. It was observed that GH therapy was initiated in these patients at a mean age of 10.3 ± 3.1 years; the initial height SDS was better. FH of 45,X and non-45,X cases were similar. In the study, GH therapy that was initiated at an early age in patients with good initial height SDS increased the gain of FH and FH SDS. Therefore, initiating GH therapy at an early age in patients with TS is important for height gain. ∆ Height SDS was better in cases that underwent late pubertal induction. Karyotype did not have a predictive effect on height prognosis.
2026-04-01 | Clinical Profile and Response to Recombinant Growth Hormone in Girls with Turner Syndrome: Experience from a Tertiary Care Centre in North India.
We aimed to describe the clinical presentation and response to recombinant growth hormone (rGH) in Indian girls with Turner syndrome (TS). This retrospective study included 33 girls with TS attending a tertiary care hospital in Northern India between 2004 and 2023. Data on clinical presentation, cytogenetics and follow-up were retrieved from clinic records. In addition, auxological data was analysed for girls who received rGH therapy. The mean age at presentation was 9.8 ± 3.9 years (range 2-17.7 years). 57.6% had classical TS, whereas, 42.4% had variant TS karyotypes. The commonest presenting features were short stature (100%) and delayed puberty (27.3%). Autoimmune hypothyroidism and celiac disease were the commonest associated co-morbidities. Pubertal induction with estradiol was done in seven patients. Sixteen (48.5%) patients received rGH at a mean starting dose of 0.29 mg/kg/week. The mean age and bone age (BA) at rGH initiation were 10.0 ± 3.3 years and 8.3 ± 3.0 years, respectively. There were significant improvements in Turner's height standard deviation scores (SDS) (-0.7 to 0.19; P = 0.003), BA (8.3 ± 3.0 to 10.2 ± 2.9; P = 0.003) and predicted adult height (PAH) (142.2 cm to 147.4 cm; P < 0.001) over a median duration of rGH therapy of 16 months (IQR 6-51 months). There was a strong positive correlation between height gain and duration of rGH therapy (r = 0.967; P < 0.001). North Indian girls with TS demonstrate a good response to rGH with improvements in height SDS, PAH, and skeletal growth. The duration of rGH significantly impacts height gain; early initiation is therefore crucial for attaining near-normal final height.
cell therapies
2026-06-18 | Live birth after oocyte cryopreservation and preimplantation genetic testing in a woman with mosaic Turner syndrome: A case report.
Turner syndrome (TS) is associated with progressive ovarian insufficiency, and fertility preservation (FP) remains difficult even in women with mosaic karyotypes. We report a live birth achieved after oocyte cryopreservation with 3.5 years of storage and preimplantation genetic testing for aneuploidy (PGT-A) in a woman with mosaic TS (45,X[4%]/46,XX[96%]). At 34 years of age, she underwent controlled ovarian stimulation for FP, which yielded nine mature oocytes that were vitrified. After 3.5 years of storage, all oocytes survived warming and were fertilized using intracytoplasmic sperm injection. Four blastocysts developed and underwent PGT-A, which identified two euploid embryos, one aneuploid embryo, and one mosaic embryo. Transfer of a single euploid blastocyst resulted in an uncomplicated term pregnancy and the delivery of a healthy male infant. To our knowledge, this is the first reported live birth in Korea achieved using cryopreserved oocytes in a woman with mosaic TS.
2026-06-06 | Functional Ovarian Tissue in a Child with Mosaic Turner Syndrome and Y Chromosome Material: Case Report.
Prophylactic bilateral gonadectomy is typically recommended for girls with mosaic Turner syndrome with Y chromosome (TS + Y) due to risk for gonadoblastoma. However, reports demonstrating lower malignancy rates and cases of spontaneous puberty have prompted reconsideration. An 8-year-old girl was found to have TS + Y, with genetic analysis showing absence of Y chromosome short arm material. Her anti-müllerian hormone declined over three months, indicating decrease in ovarian reserve. She underwent bilateral gonadectomy with ovarian tissue cryopreservation and was found to have functional ovarian tissue. In contrast to most TS + Y cases, our patient demonstrated functional ovarian tissue. Characterization of which Y chromosome segments are present may predict gonadal tissue type and gonadoblastoma risk, assisting decision-making regarding gonadectomy timing and the option for fertility preservation.
2026-06-04 | Ovarian Tissue Cryopreservation in Turner Syndrome: A Narrative Review
Turner syndrome, caused by complete or partial monosomy X, leads to gonadal dysgenesis and accelerated follicular atresia, resulting in premature ovarian insufficiency in over 95% of affected individuals. Ovarian tissue cryopreservation (OTC) has emerged as a potential fertility preservation strategy, particularly for prepubertal girls ineligible for ovarian stimulation. Predictors of residual fertility include mosaic karyotype, higher anti-Müllerian hormone and inhibin B levels, lower FSH, evidence of pubertal development, and ultrasonographically visible ovaries, though cryptic gonadal mosaicism may obscure true reproductive potential. While donor oocyte IVF remains the most effective route to pregnancy, autologous oocyte cryopreservation is feasible in selected postpubertal patients, and OTC offers the advantage of earlier intervention without requiring hormonal stimulation. The procedure involves laparoscopic oophorectomy, cortical tissue preparation, cryopreservation, and subsequent reimplantation, with the possibility of preserving not only fertility but also endocrine function and natural pubertal development. However, ovarian tissue in Turner syndrome frequently demonstrates poor follicular morphology and reduced reserve, and significant limitations remain, including premature follicular depletion, technical challenges in tissue processing, suboptimal revascularization after transplantation, and uncertain functional restoration. Psychological and ethical considerations further complicate decision-making, particularly in young patients. Prospective studies such as Turner Fertility support procedural feasibility, yet live birth outcomes remain rare. Overall, OTC may represent a meaningful fertility preservation option in carefully selected individuals with Turner syndrome, but current evidence is limited and individualized, multidisciplinary counselling is essential to align interventions with realistic expectations.
2026-05-25 | Live birth after oocyte donation in women with Turner syndrome compared with other causes of premature ovarian insufficiency: a retrospective cohort study.
To compare live birth rates after in vitro fertilization (IVF) with oocyte donation between women with Turner syndrome and women with premature ovarian insufficiency (POI) of other etiologies and to evaluate the relationships between uterine volume, duration of hormone replacement therapy (HRT), and obstetric outcomes. This retrospective cohort study included 97 women with POI undergoing IVF with oocyte donation at a university-affiliated tertiary care center between 2007 and 2023, including 30 women with Turner syndrome and 67 with POI of other etiologies. Artificial endometrial preparation cycles were used for all recipients. Uterine volume was measured by transvaginal ultrasound prior to the first embryo transfer. Primary outcome was live birth per embryo transfer. Secondary outcomes included live birth according to embryo transfer rank, associations between uterine volume and obstetric or neonatal outcomes, and the relationship between uterine volume and duration of prior HRT. A total of 245 embryo transfers were performed. Live birth rates per embryo transfer were comparable between women with Turner syndrome and those with other POI etiologies (29% vs. 27%). However, women with Turner syndrome had a significantly lower probability of achieving live birth at the first embryo transfer (adjusted odds ratio [OR] 0.09; 95% confidence interval [CI] 0.01-0.64), whereas no significant difference was observed after three or more transfers. Median uterine volume prior to IVF did not differ significantly between groups, despite a substantially longer duration of prior HRT in women with Turner syndrome (15.5 vs. 3.0 years). No significant association was observed between uterine volume and duration of HRT in either group. Among singleton pregnancies, decreasing uterine volume was associated with increased risks of preeclampsia, intrauterine growth restriction, non-cephalic presentation, and adverse neonatal outcomes. Women with Turner syndrome achieve live birth rates after IVF with oocyte donation comparable to those of women with other POI etiologies, although more embryo transfer attempts may be required. No clear association between uterine volume and duration of HRT was observed. However, decreasing uterine volume was associated with adverse obstetric outcomes, highlighting the importance of early hormonal management and careful obstetric surveillance in this population.
2026-04-15 | Successful Kidney Transplantation in Turner Syndrome: A Case for Feasibility and Favorable Outcomes.
Turner syndrome (TS) leads to various abnormalities, including renal malformations that can progress to end-stage renal disease (ESRD). Although rarely performed in patients with TS, renal transplantation offers significant benefits over dialysis. We report the case of a 34-year-old female with TS and ESRD who underwent a successful living-donor kidney transplantation. Preoperative imaging revealed atrophic, malformed native kidneys located entirely in the pelvic region. A suitable graft bed was meticulously created in the right iliac fossa without the need for native nephrectomy. At the 9-month postoperative follow-up, the patient demonstrated excellent and stable graft function. This case highlights the feasibility of kidney transplantation in patients with TS and underscores the importance of careful preoperative planning and a multidisciplinary approach to overcome unique anatomical challenges.
other
2024-02-25 | System biology approach to delineate expressional difference in the blood mononuclear cells between healthy and Turner syndrome individuals
Abstract Background Turner syndrome (TS) is a rare disorder associated either with complete or partial loss of one X chromosome in women. The information on the genotype–phenotype relationship in TS is inadequate. Comparing the healthy and Turner syndrome patients may help elucidate the mechanisms involved in TS pathophysiology. Gene expression differences between healthy and individuals with Turner syndrome were characterized using the systems-biology approach of weighted gene coexpression network analysis (WGCNA) on 182 microarray peripheral mononuclear blood samples (PBMC). Results The coexpression networks of healthy and TS had scale-free topology that ensures network robustness. In the process, five modules were preserved between healthy and TS, which carry several genes common in each module. Two of them, SMCHD1 and PGK1, have already been reported to be involved in TS. Previously reported genes of TS, specifically, PTPN22, RPS4X, CSF2RA, and TIMP1, were missing in their respective modules. Dysfunction, differential expression, or absence of these genes could lead to a progressive disruption of molecular pathways leading to the pathophysiology of TS. Indeed, we observed a significant difference in the functions of these modules when compared within and across the healthy and TS samples. We identified four clusters in the PPI network constructed from the top 15 KME enriched in significant functions. Conclusion Overall, our work highlights the potential molecular functions, pathways, and molecular targets of TS that can be exploited therapeutically in the human healthcare system.
2021-09-08 | Reproductive outcomes after preimplantation genetic testing in mosaic Turner syndrome: a retrospective cohort study of 100 cycles.
The purpose of this study is to explore the reproductive outcomes of women with Turner syndrome (TS) in preimplantation genetic testing (PGT) cycles. A retrospective study of 100 controlled ovarian stimulating cycles, 68 TS (sixty-four mosaic Turner syndrome (MTS) and four pure Turner syndrome (PTS)) women underwent PGT was conducted from 2013 to 2018. Embryo X chromosome abnormal rates of TS women were significantly higher than women with normal karyotype (7.04 vs 1.61%, P<0.01). Cumulative live birth rates (CLBR) after PGT-NGS treatment were lower in TS than control (31.15 vs 45.59%, P<0.05). Clinical pregnancy rates per transfer (CPR), miscarriage rates (MR) and live birth rates per transfer (LBR) remained comparable between TS and control group. Reproductive outcomes (X chromosome abnormal rates, CPR, MR, LBR and CLBR) among low (<10%), medium (10-50%) and high (>50%) level 45,X mosaicism groups were not statistically different. To avoid high risk of embryo X chromosome abnormalities, prenatal or preimplantation genetic testing should be recommended to mosaic or pure TS patients.
small molecules
2026-08-17 | Pulmonary Hypertension Workup Unraveling a Rare Anomaly in Turner Syndrome.
Turner syndrome (TS) is associated with congenital heart disease, most commonly a bicuspid aortic valve and coarctation of the aorta; however, partial anomalous pulmonary venous return (PAPVR) remains an underrecognized cardiovascular anomaly. PAPVR, in which one or more pulmonary veins drain into the systemic venous circulation, can cause left-to-right shunting, right-sided chamber dilation, and pulmonary hypertension (PH). We report the case of a 51-year-old woman with TS and hypertension who presented with dyspnea and an estimated right ventricular systolic pressure of 55 mmHg on echocardiography. Right heart catheterization (RHC) showed severe PH, with a mean pulmonary artery pressure of 53 mmHg, a pulmonary capillary wedge pressure of 16 mmHg, and a pulmonary vascular resistance of 2.1 Wood units, along with unexpectedly high pulmonary artery oxygen saturations suggestive of a left-to-right shunt. Cardiac MRI demonstrated right-sided enlargement with a pulmonary-to-systemic flow ratio (Qp:Qs) of approximately 3.0 but no intracardiac defect. CT confirmed PAPVR, with the right superior and middle pulmonary veins draining into the superior vena cava and the left superior pulmonary vein draining into the brachiocephalic vein. She improved clinically with tadalafil and furosemide and was referred for surgical evaluation. In patients with TS and unexplained PH, an unexpectedly high pulmonary artery oxygen saturation on RHC should raise suspicion for an occult left-to-right shunt. When no intracardiac defect is identified, multimodality imaging with cardiac MRI and CT can reveal extracardiac shunt lesions such as PAPVR and guide timely referral for definitive management.
2026-06-26 | Transdermal versus oral hormone replacement therapy and bone mass density in Turner syndrome patients: a pilot study.
Women with Turner syndrome (TS) are at increased risk of reduced bone mineral density (BMD) due to primary ovarian insufficiency. This study aimed to assess longitudinal changes in BMD in TS patients receiving oral or transdermal hormone replacement therapy (HRT) and to identify factors associated with bone density decline. This retrospective pilot study included 40 TS patients treated with oral or transdermal estradiol. The median age was 22 years in both the transdermal (20-30) and oral (20-27) groups. Median BMI was 23.1 (21.1-25.5) and 25.4 (22.1-29.1), respectively. Dual-energy X-ray absorptiometry (DEXA) of the lumbar spine and femoral neck was performed at baseline and follow-up. The primary outcome was the t-score at both sites. Univariable and multivariable logistic regression analyses were used to identify factors associated with declining t-scores. At baseline, 38.3% of patients had osteopenia, and 3.3% had osteoporosis. During follow-up, a decline in t-scores at at-least one skeletal site was observed in 47.5% of patients. No significant differences were found between oral and transdermal estradiol therapy regarding absolute t-scores, t-score changes, or the proportion of patients with declining t-scores (all p > 0.05). In multivariable analysis, lower vitamin D levels at follow-up were independently associated with declining t-scores. In TS patients, the route of estradiol administration did not significantly affect long-term BMD outcomes. Despite HRT, a substantial proportion of patients experienced bone loss. Vitamin D status has emerged as the most relevant modifiable factor associated with declining BMD, highlighting the need for bone health management beyond HRT.
2026-05-18 | Integrative Bioinformatics Analyses Reveal X Chromosome Inactivation Escape Genes Dosage Dysregulation Is the Primary Contributor to Turner Syndrome.
Turner syndrome is a rare disorder resulting from abnormalities in the number or structure of a single X chromosome. It stands as the sole survivable monosomy observed in humans. Individuals affected by Turner syndrome commonly face significant complications, including impaired gonadal development, short stature, and intellectual disabilities. Despite extensive research, the complete understanding of the pathogenesis behind Turner syndrome remains elusive. This study aimed to elucidate the molecular mechanisms of Turner syndrome by identifying key X chromosome inactivation escape genes and exploring their potential contributions to genotype-phenotype correlations and therapeutic targets through integrative bioinformatics analyses. The study included three RNA-seq datasets, consisting of 72 patients with Turner syndrome and 58 individuals with normal cytogenetics. Differentially expressed gene analysis, protein-protein interaction network analysis, and functional enrichment analysis were conducted to ascertain hub genes. Furthermore, pivotal lncRNAs and transcription factors were identified through competitive endogenous RNA network analysis and transcription factor enrichment analyses. This study made a significant contribution by exploring the relationship between Turner syndrome genotypes and various phenotypes at the transcriptomic level. We found hub genes associated with hormone regulation, including growth hormone. Moreover, we highlighted 10 crucial X chromosome inactivation escape genes (ASMTL, CD99, DHRSX, EIF1AX, JPX, KDM5C, KDM6A, SLC25A6, XIST, and ZFX), which may serve as core pathogenic factors in Turner Syndrome. Additionally, based on our findings, we proposed certain drugs as potential new therapeutic strategies for Turner Syndrome. Our study provides substantial evidence supporting the correlation between genotype and various phenotypes in Turner Syndrome. Furthermore, we shed light on the potential pathogenic significance of X chromosome inactivation escape genes. These findings open up new possibilities for therapeutic interventions.
2026-04-01 | Thoracic spinal anesthesia for emergency derivative colostomy in a turner syndrome patient
Sir, We read with great interest the recent case report by Guillarducci et al., entitled “Anesthetic implications of elective cesarean section in a parturient with Noonan syndrome and complex cardiomyopathy: A case report,” which highlighted the importance of individualized anesthetic planning and demonstrated that neuraxial anesthesia can represent a safe and effective approach in selected high-risk patients.[1] Notably, Noonan syndrome is characterized by a Turner phenotype, reflecting the shared anatomical and cardiovascular features between these two conditions, which may significantly impact anesthetic management.[1] Turner syndrome (TS) is a genetic disorder caused by sex chromosomal abnormalities affecting women and is associated with a wide spectrum of anatomical and physiological alterations, particularly involving the airway and cardiovascular system.[2] Short webbed neck, maxillary and mandibular hypoplasia, reduced tracheal length, and altered tracheal anatomy may contribute to difficult airway management.[3,4] Additionally, congenital cardiovascular abnormalities and pulmonary arterial hypertension may significantly increase perioperative morbidity and mortality, particularly during general anesthesia.[5] Therefore, thorough understanding of these anatomo-physiological abnormalities is essential to ensure safe anesthetic care. Neuraxial anesthesia may represent a valuable alternative to general anesthesia in selected high-risk patients, allowing avoidance of airway manipulation and reduction of hemodynamic stress.[3,4] However, short stature requires careful individualization of local anesthetic dosing, and spinal deformities such as scoliosis may increase the technical difficulty of neuraxial block placement. We describe the case of a 62-year-old ASA IV woman with TS, who underwent emergency derivative colostomy for intestinal obstruction. The patient presented multiple severe comorbidities, including heart failure with moderate left ventricular dysfunction, moderate precapillary pulmonary arterial hypertension (PAP 65 mmHg), persistent atrial fibrillation on anticoagulation therapy, end-stage renal disease on hemodialysis, chronic obstructive pulmonary disease requiring oxygen therapy, hypothyroidism, neurogenic bladder, chronic iron-deficiency anemia due to colonic angiodysplasia, adrenal adenoma, and previous endometrial carcinoma. After obtaining informed consent, thoracic spinal anesthesia was performed in the sitting position using a 25 G Whitacre needle at the T9–T10 interspace, administering a low dose of bupivacaine 0.25% 8 mg with dexmedetomidine 5 mcg as adjuvant. Minimal sedation with midazolam 1 mg was provided. Hemodynamic stability was maintained using continuous norepinephrine infusion (0.05 µg/kg/min), guided by minimally invasive monitoring. The surgical procedure lasted approximately 70 min. The patient maintained spontaneous breathing and stable vital parameters throughout the operation. No intraoperative or postoperative complications occurred. Postoperative analgesia required only acetaminophen, without opioid administration. This case further supports the concept that neuraxial anesthesia, when carefully individualized, may represent a safe and effective anesthetic strategy in high-risk patients with TS, particularly in those presenting Turner phenotype features associated with increased risks of general anesthesia. Careful patient selection, dose adjustment, and experienced anesthetic management remain essential to optimize perioperative safety in this challenging population. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
2026-03-27 | Semaglutide Plus Low-Dose Metformin Combination Therapy for the Treatment of Obesity and Prediabetes in a Woman with Partial Deletion of the X Chromosome Long Arm.
Background and Clinical Significance: Over the last two decades, glucagon-like peptide-1 (GLP-1) receptor agonists have dramatically improved the management of type 2 diabetes mellitus and obesity. Currently, little is known about the use of semaglutide (a second-generation GLP-1 receptor agonist) in patients with X chromosome abnormalities. Herein, we describe the therapeutic use of semaglutide in a woman with a partial deletion of the X chromosome long arm (partial Xq deletion) and comorbid obesity. We also conducted a narrative mini-review on overweight, obesity and common metabolic derangements in patients with partial Xq deletions and Turner syndrome. Case Presentation: A 65-year-old Italian woman with a partial Xq deletion, class 1 obesity, insulin resistance, prediabetes, hypercholesterolemia and metabolic dysfunction-associated steatotic liver disease (MASLD) was referred to our Institution for persistent difficulty in managing excess body weight despite regular adherence to different structured physical activity programs and hypocaloric diets. Therefore, we prescribed a combination therapy based on low-dose metformin (500 mg/day) and once-weekly subcutaneous semaglutide (as an adjunct to lifestyle intervention). At 5 months after initiation of the combination therapy, blood tests showed metabolic improvements, including improvement of prediabetes (0.3-percentage-point reduction in glycated hemoglobin [HbA1c] values) and normalization of markers of insulin sensitivity and insulin resistance (QUICKI, HOMA-IR and TyG index). At 8 months, the patient showed substantial weight loss, which amounted to 13.8 kg (percent total body weight loss: 20.95%), and was accompanied by a notable reduction in waist circumference (-14.1 cm). Moreover, body mass index (BMI)-based weight status improved from class 1 obesity to overweight: BMI value of 25.1 kg/m2 at 8 months vs. 31.8 kg/m2 at baseline (near-normalization of BMI values). Bioelectrical impedance analysis (BIA) revealed that the patient's overall weight loss consisted of 74.6% fat mass (FM) loss (-10.3 kg) and 25.4% fat-free mass (FFM) loss (-3.5 kg). Despite the expected FFM reduction in absolute terms, percent FFM increased at 8 months (+9.6%). This increase in percent FFM was accompanied by a reduction in percent FM at 8 months (-9.6%), indicating an overall improvement in body composition. Normalization of percent FM and FFM values (28.6% and 71.4%, respectively) was also achieved at 8 months. These body composition changes are in line with those observed in clinical trials investigating the use of semaglutide in patients with overweight or obesity. At 6 months, an abdominal ultrasound also showed the disappearance of the sonographic characteristics suggestive of mild-to-moderate hepatic steatosis. Low-dose metformin (500 mg/day) and subcutaneous semaglutide (up to a weekly dose of 1.7 mg) were well tolerated by the patient. Conclusions: To the best of our knowledge, this is the first case documenting the effective use of once-weekly subcutaneous semaglutide plus low-dose metformin combination therapy for the treatment of obesity and prediabetes in a woman with a partial Xq deletion. Large prospective cohort studies are warranted to better investigate the safety and efficacy profile of semaglutide (alone or in combination with metformin) in patients with numerical and structural X chromosome abnormalities, comorbid overweight/obesity and related metabolic disorders.
gene therapies
2026-07-02 | Influence of X-Chromosome Inactivation in Pathogenesis of Turner Syndrome
Turner syndrome (TS), a disorder caused by the complete or partial absence of an X chromosome, exhibits significant clinical variability that cannot be fully explained by chromosomal anomalies alone. This narrative review highlights the crucial role of epigenetic mechanisms, particularly X-chromosome inactivation (XCI), in shaping the TS phenotype. The haploinsufficiency of genes that normally escape XCI is a primary driver of TS features. The specific epigenetic consequences depend on the chromosomal anomaly. In complete monosomy (45,X), the absence of escape-mediated dosage compensation genes from a second X chromosome amplifies haploinsufficiency across X-linked escape genes. Isochromosome Xq (i(Xq)) variants involve the loss of the short arm (Xp) and duplication of the long arm (Xq), creating a dual dosage imbalance with extreme XCI skewing. Carriers of i(Xq) also have a heightened risk for autoimmune disorders compared to those with 45,X TS. For ring-X chromosomes (r(X)), which are mitotically unstable, the functional status of the XIST gene is critical. If the ring is XIST-negative, it remains transcriptionally active, resulting in functional disomy and a more severe phenotype with pronounced neurodevelopmental and craniofacial features. Ultimately, the clinical heterogeneity in TS arises from a complex interplay of the specific chromosomal structure, tissue-specific mosaicism, XIST function, and variable escape from XCI, defining TS as a disorder of epigenetic and gene-regulatory imbalance. However, future research requires a better understanding of the complex mechanism of X-chromosome inactivation.
2026-05-29 | Sleep Disorders in Klinefelter Syndrome and Other Sex Chromosome Aneuploidies: A Narrative Review.
Sex chromosome aneuploidies (SCAs) are among the most frequent types of chromosomal aneuploidies and include Klinefelter syndrome (47,XXY and higher-grade variants), 47,XYY syndrome, Turner syndrome (45,X), and trisomy X (47,XXX). These conditions share complex neurodevelopmental, endocrine, and metabolic features with important implications for reproductive and general health. Sleep plays a pivotal role in neurocognitive functioning, mood regulation, cardiometabolic homeostasis, and hypothalamic-pituitary-gonadal axis activity, yet sleep disorders remain poorly characterized and under-recognized in SCAs. This narrative review synthesizes current evidence on sleep disturbances in SCAs, with particular emphasis on male phenotypes, while integrating evidence from female SCAs to highlight shared mechanisms and overlapping sleep phenotypes. Available data indicate an increased prevalence of insomnia, sleep fragmentation, excessive daytime sleepiness, circadian rhythm disturbances, and sleep-disordered breathing from childhood through adulthood. In Klinefelter syndrome, sleep alterations appear multifactorial, arising from the interaction between hypogonadism, obesity, psychiatric vulnerability, neurocognitive deficits, and possible circadian and melatonin dysregulation. Evidence in 47,XYY and higher-grade male SCAs, although limited, suggests a predominant contribution of neurodevelopmental and behavioral factors. Emerging findings also implicate oxidative stress as a potential mechanistic link between sleep disruption, metabolic dysregulation, and neurocognitive impairment. Overall, the literature is fragmented and methodologically heterogeneous, underscoring the need for systematic sleep screening and integrated multidisciplinary management within andrological care pathways to improve long-term health and reproductive outcomes in individuals with SCAs.
2026-04-01 | Turner syndrome and acute type A aortic dissection: a national inpatient analysis of risk and outcomes.
Although acute type A aortic dissection (ATAAD) is a recognised complication of Turner syndrome, population-level data describing its prevalence and outcomes remain limited. We queried the National Inpatient Sample (2002-2020) and generated three groups: TS + ATAAD+, TS + ATAAD-, and TS-ATAAD+ in our retrospective observational cohort study. Primary outcomes were ATAAD hospital admission rate and in-hospital mortality; secondary outcomes included length of stay. Sampling weights were applied to all analyses. A total of 51,426 Turner syndrome hospitalisations were identified. Median ages were 40 years (interquartile range 31-50) for TS + ATAAD+ and 32 years (interquartile range 9-49) for TS + ATAAD- (p < 0.001). Overall, 0.27% of Turner syndrome hospitalisations presented with ATAAD. Compared with TS + ATAAD-, those with ATAAD had higher mortality (13.1% vs 2.1%, p < 0.001) and longer length of stay (median 8 vs 3 days, p < 0.05). Rates of bicuspid aortic valve (34.3% vs 3.5%, p < 0.001), hypertension (46.0% vs 25.7%, p < 0.05), and complete heart block (14.6% vs 0.8%, p < 0.001) were also higher. Multivariable analysis showed bicuspid aortic valve (adjusted odds ratio 24.31, 95% CI 8.8-67.3) and age (adjusted odds ratio 1.02, 95% CI 1.01-1.04) predicted ATAAD. Compared with TS-ATAAD+ patients, those withTS + ATAAD+ were younger (40 vs 68 years, p < 0.001), while mortality, length of stay, hypertension, and bleeding rates were similar. ATAAD is highly lethal in patients with and without Turner syndrome. In Turner syndrome, ATAAD is associated with higher mortality, longer hospitalisation, and higher rates of bicuspid valve disease and hypertension.
2026-02-12 | Ultra-performance Liquid Chromatography-mass Spectrometry-based metabolic profiling of prepubertal children with Turner syndrome.
This research aims to characterize the metabolic profiles of prepubertal patients with TS to elucidate the potential impact of X chromosome haploinsufficiency on glycolipid metabolism. Fouty-nine prepuberty TS and 50 age-, sex- and BMI standard deviations scores (SDS)-matched healthy children (HC) were enrolled. Untargeted ultra-performance liquid chromatography-coupled mass spectroscopy was performed in all participants. Differentially expressed metabolites (DEMs) were identified and annotated using the KEGG and HMDB databases. Correlation analyses were conducted to explore associations between DEMs and relevant clinical parameters. Logistic regression models were performed to evaluate the potential impact of the interaction between X-chromosome haploinsufficiency and metabolite abnormalities on metabolic status. Metabolomics analyses indicated separation between TS and HC groups with 70 DEMs enriched in caffeine metabolism, purine metabolism, and insulin resistance pathways. Among TS, 34 DEMs were found to be correlated with height, weight, glucose and lipid metabolism, and sex hormone levels. Three DEMs-sodium cholate, N-arachidonoyl-L-serine, and N1-pyrazin-2-yl-4-chlorobenzamide--were identified to interact with X chromosome haploinsufficiency in influencing metabolic status. Prepubertal children with TS exhibit distinct metabolic profiles, with DEMs enriched in caffeine metabolism, purine metabolism, and insulin resistance pathways. These metabolites show correlations with clinical parameters and demonstrate interactions with X chromosome haploinsufficiency affecting metabolic health. This study described the distinctive metabolic profiles of TS children for the first time. The impact of X chromosome haploinsufficiency on glycolipid metabolism was elucidated through a study of prepubertal TS children. Three novel metabolites were identified with significant interaction effects with X chromosome haploinsufficiency on glycolipid metabolic status.
2025-12-03 | Exercise capacity in girls with Turner syndrome.
Data on exercise capacity of pediatric patients with Turner syndrome (TS) is scarce. This study was aimed at evaluating the cardiopulmonary response to exercise in girls with TS aged 8 to 18 years. In this prospective, single-center case-control cohort study girls with TS were matched to healthy controls based on gender, age, and weight. All girls performed a maximal incremental cardiopulmonary exercise test (CEPT) on an electromagnetically braked cycle ergometer. Key variables measured included peak oxygen uptake (VO2 peak) and maximal workload both expressed as percentages of predicted values based on gender, age, and weight. O2 pulse is expressed in milliliters per heartbeat. Twenty-one girls with TS were included and matched with 21 control patients. Girls with TS demonstrated significantly lower VO2 peak values (% of predicted) compared to controls (mean difference: - 10.3%, p = 0.014). Similarly, maximal workload was significantly reduced in the TS group (mean difference: - 17.6%, p = 0.002). A general linear model confirmed that group status (TS vs. control) was a significant predictor of both VO2 peak and maximal workload, independent of age and weight. No significant differences were observed in maximal heart rate or blood pressure between the two groups. O2 pulse (ml/beat) was significantly lower in patients with TS (7.7 ± 1.2 ml/beat) versus healthy controls (8.6 ± 1.4 ml/beat, p = 0.03).Conclusion: Girls with TS exhibit a reduced exercise capacity compared to their healthy peers, as evidenced by lower VO2 peak, maximal workload and O2 pulse during standardized CPET. Further research on pathophysiology, evolution over time, and impact of targeted interventions is needed.
proteins
2026-06-29 | Model-based somapacitan dosing and IGF-I response in children born SGA or with ISS, Noonan or Turner syndromes.
The weekly insulin-like growth factor I (IGF-I) profile for children and adolescents treated with long-acting growth hormone differs from that of daily growth hormone (GH). The objective of this study is to provide guidance on the use of once-weekly somapacitan and IGF-I monitoring in prepubertal short children and adolescents born small for gestational age (SGA) or with idiopathic short stature (ISS), Noonan syndrome (NS), or Turner syndrome (TS). Modeling, including population pharmacokinetic/pharmacodynamic (PK/PD) modeling, were utilized, analyzing IGF-I data from 4 clinical studies, including 2 phase 3 trials (REAL8: NCT05330325; REAL9: NCT05723835) involving children and adolescents born SGA (N = 80), ISS (N = 69), NS (N = 62), and TS (N = 79), along with additional data from phase 2 (REAL5: NCT03878446, N = 59) and phase 1 trials (NCT01973244, N = 24). Relationships between somapacitan dose, exposure, baseline IGF-I SD score (SDS), and height velocity (HV) were established in children born SGA, with similar responses anticipated for those with ISS, NS, or TS. A linear model enabled the estimation of average weekly IGF-I exposure from a single sample collected during the somapacitan dosing interval. IGF-I SDS simulations support flexible dosing changes while maintaining a minimum of 4 days between doses. Somapacitan 0.24 mg/kg/week produced similar IGF-I SDS changes and height velocity increases as daily GH in prepubertal short children and adolescents born SGA or with ISS, NS, or TS. The results support that the guidance already established for GHD regarding somapacitan initiation, dosing flexibility, and IGF-I monitoring remain appropriate for prepubertal short children and adolescents born SGA or with ISS, NS, or TS.
2026-06-15 | First reported case of Turner syndrome with Krabbe disease in a child: a case report.
Turner syndrome (TS) is a congenital sex chromosome disorder. Krabbe disease (KD) is a rare autosomal recessive neurometabolic disorder. Here, we reported the first case of a child with both conditions. A girl presenting as short stature was diagnosed with 45,X TS at the age of 9 years, showed significant height improvement with recombinant human growth hormone (rhGH) therapy, which was well-tolerated without drug-related adverse events. At age 14 years, she was hospitalized with nausea, abdominal pain, dizziness, fatigue, and weight loss, and was diagnosed with secondary adrenal insufficiency. Comprehensive evaluation ruled out TS and prior rhGH therapy as causes for secondary adrenal insufficiency, prompting consideration of other inherited metabolic disorders. Ultimately, the multidisciplinary team conducted an evaluation confirming KD through genetic testing and detection of below-normal galactocerebrosidase enzyme activity (40.6 nmol/17h/mg protein). Since her height improvement was satisfactory, rhGH therapy was temporarily discontinued. After evaluation, she was deemed ineligible for hematopoietic stem cell transplantation. We initiated hydrocortisone replacement therapy to address her adrenal insufficiency symptoms. Overall, this case highlighted that secondary adrenal insufficiency could serve as an atypical clinical manifestation of KD. Furthermore, rhGH demonstrated satisfactory efficacy and safety in improving short stature in patient with 45,X TS.
2026-06-05 | Growth hormone therapy and near-final height in SHOX deficiency and turner syndrome: a real-world single-center retrospective cohort study.
Short stature homeobox-containing (SHOX)-gene haploinsufficiency causes short stature both in isolated SHOX deficiency and in Turner syndrome (TS), yet head-to-head data on growth-hormone (GH) outcomes remain scarce. We therefore compared growth response and near-final height (NFH) after GH therapy between girls with SHOX deficiency and those with TS. Single-centre retrospective cohort study. In this single-centre retrospective cohort, we reviewed 44 pre-pubertal girls who received daily GH (mean 0.045 mg/kg/day) between 2015 and 2024 and subsequently reached NFH (bone age ≥ 14 y; height velocity < 2 cm/year). Ten had molecularly confirmed SHOX deficiency and 34 had karyotype-proven TS. Baseline auxology, annual height velocity, pubertal timing, treatment duration, NFH standard-deviation score (SDS) and total height SDS gain were analysed. Mean chronological and bone ages at GH initiation were similar (10.7 ± 1.9 vs 10.4 ± 2.7 years). Baseline height SDS was lower in TS (-3.51 ± 1.0) than in SHOX (-2.66 ± 0.8). First-year growth velocity was higher in SHOX (8.55 ± 1.4 cm/year) than TS (6.72 ± 1.9 cm/year; p = 0.01). Puberty began earlier in SHOX (11.6 ± 1.3 years) than TS (13.7 ± 1.5 years; p < 0.01), and GH exposure was shorter (2.00 ± 0.4 vs 4.38 ± 2.3; p < 0.01). Observed NFH-SDS was similar between groups (SHOX - 2.46 ± 1.2 vs TS - 2.47 ± 1.0). Unadjusted height-SDS gain was greater in TS (1.04 ± 0.1 vs 0.20 ± 0.2; p = 0.04). In exploratory ANCOVA models adjusting for baseline age, baseline height SDS, and GH treatment duration, adjusted height-SDS gain did not differ significantly between groups. TS was associated with a greater unadjusted height-SDS gain, whereas SHOX deficiency was characterized by earlier puberty and shorter GH exposure. Although observed NFH-SDS was similar, these findings highlight how differences in pubertal timing and treatment duration may influence growth outcomes in routine clinical practice and should be interpreted as reflecting real-world growth trajectories rather than intrinsic biological responsiveness to GH therapy. • Growth hormone therapy is an established treatment for short stature in both SHOX deficiency and Turner syndrome. • Treatment response is influenced by several factors, including age at treatment initiation and pubertal development. • This study provides a real-world comparison of growth hormone treatment outcomes in girls with SHOX deficiency and Turner syndrome. • Spontaneous pubertal progression in SHOX deficiency versus medically induced puberty in Turner syndrome may substantially influence the duration of the therapeutic growth window and the observed growth response.
2026-04-25 | Final Height in Patients with Turner Syndrome Treated With Growth Hormone Therapy.
Turner syndrome (TS) is the most common sex chromosome abnormality in girls. Short stature is the most distinctive feature. This study aimed to evaluate factors affecting final height (FH) in patients with TS who received growth hormone (GH) therapy and achieved their final height (FH). About 48 patients with TS who received GH therapy and reached their FH were included and examined retrospectively. Initial height, standard deviation score (SDS), FH, and FH SDS measurements of the patients were obtained. Additionally, factors affecting FH were analyzed. Growth hormone was administered at a dose of 45.6 ± 6.2 (min-max: 34-69) μg/kg/day at a mean age of 11.7 ± 2.9 years. The duration of therapy was 4.3 ± 1.4 years. The mean FH of the patients was 147.80 ± 5.98 cm. About 29.2% (n=14) of the patients reached a height above the thirdpercentile. It was observed that GH therapy was initiated in these patients at a mean age of 10.3 ± 3.1 years; the initial height SDS was better. FH of 45,X and non-45,X cases were similar. In the study, GH therapy that was initiated at an early age in patients with good initial height SDS increased the gain of FH and FH SDS. Therefore, initiating GH therapy at an early age in patients with TS is important for height gain. ∆ Height SDS was better in cases that underwent late pubertal induction. Karyotype did not have a predictive effect on height prognosis.
2026-04-01 | Clinical Profile and Response to Recombinant Growth Hormone in Girls with Turner Syndrome: Experience from a Tertiary Care Centre in North India.
We aimed to describe the clinical presentation and response to recombinant growth hormone (rGH) in Indian girls with Turner syndrome (TS). This retrospective study included 33 girls with TS attending a tertiary care hospital in Northern India between 2004 and 2023. Data on clinical presentation, cytogenetics and follow-up were retrieved from clinic records. In addition, auxological data was analysed for girls who received rGH therapy. The mean age at presentation was 9.8 ± 3.9 years (range 2-17.7 years). 57.6% had classical TS, whereas, 42.4% had variant TS karyotypes. The commonest presenting features were short stature (100%) and delayed puberty (27.3%). Autoimmune hypothyroidism and celiac disease were the commonest associated co-morbidities. Pubertal induction with estradiol was done in seven patients. Sixteen (48.5%) patients received rGH at a mean starting dose of 0.29 mg/kg/week. The mean age and bone age (BA) at rGH initiation were 10.0 ± 3.3 years and 8.3 ± 3.0 years, respectively. There were significant improvements in Turner's height standard deviation scores (SDS) (-0.7 to 0.19; P = 0.003), BA (8.3 ± 3.0 to 10.2 ± 2.9; P = 0.003) and predicted adult height (PAH) (142.2 cm to 147.4 cm; P < 0.001) over a median duration of rGH therapy of 16 months (IQR 6-51 months). There was a strong positive correlation between height gain and duration of rGH therapy (r = 0.967; P < 0.001). North Indian girls with TS demonstrate a good response to rGH with improvements in height SDS, PAH, and skeletal growth. The duration of rGH significantly impacts height gain; early initiation is therefore crucial for attaining near-normal final height.
cell therapies
2026-06-18 | Live birth after oocyte cryopreservation and preimplantation genetic testing in a woman with mosaic Turner syndrome: A case report.
Turner syndrome (TS) is associated with progressive ovarian insufficiency, and fertility preservation (FP) remains difficult even in women with mosaic karyotypes. We report a live birth achieved after oocyte cryopreservation with 3.5 years of storage and preimplantation genetic testing for aneuploidy (PGT-A) in a woman with mosaic TS (45,X[4%]/46,XX[96%]). At 34 years of age, she underwent controlled ovarian stimulation for FP, which yielded nine mature oocytes that were vitrified. After 3.5 years of storage, all oocytes survived warming and were fertilized using intracytoplasmic sperm injection. Four blastocysts developed and underwent PGT-A, which identified two euploid embryos, one aneuploid embryo, and one mosaic embryo. Transfer of a single euploid blastocyst resulted in an uncomplicated term pregnancy and the delivery of a healthy male infant. To our knowledge, this is the first reported live birth in Korea achieved using cryopreserved oocytes in a woman with mosaic TS.
2026-06-06 | Functional Ovarian Tissue in a Child with Mosaic Turner Syndrome and Y Chromosome Material: Case Report.
Prophylactic bilateral gonadectomy is typically recommended for girls with mosaic Turner syndrome with Y chromosome (TS + Y) due to risk for gonadoblastoma. However, reports demonstrating lower malignancy rates and cases of spontaneous puberty have prompted reconsideration. An 8-year-old girl was found to have TS + Y, with genetic analysis showing absence of Y chromosome short arm material. Her anti-müllerian hormone declined over three months, indicating decrease in ovarian reserve. She underwent bilateral gonadectomy with ovarian tissue cryopreservation and was found to have functional ovarian tissue. In contrast to most TS + Y cases, our patient demonstrated functional ovarian tissue. Characterization of which Y chromosome segments are present may predict gonadal tissue type and gonadoblastoma risk, assisting decision-making regarding gonadectomy timing and the option for fertility preservation.
2026-06-04 | Ovarian Tissue Cryopreservation in Turner Syndrome: A Narrative Review
Turner syndrome, caused by complete or partial monosomy X, leads to gonadal dysgenesis and accelerated follicular atresia, resulting in premature ovarian insufficiency in over 95% of affected individuals. Ovarian tissue cryopreservation (OTC) has emerged as a potential fertility preservation strategy, particularly for prepubertal girls ineligible for ovarian stimulation. Predictors of residual fertility include mosaic karyotype, higher anti-Müllerian hormone and inhibin B levels, lower FSH, evidence of pubertal development, and ultrasonographically visible ovaries, though cryptic gonadal mosaicism may obscure true reproductive potential. While donor oocyte IVF remains the most effective route to pregnancy, autologous oocyte cryopreservation is feasible in selected postpubertal patients, and OTC offers the advantage of earlier intervention without requiring hormonal stimulation. The procedure involves laparoscopic oophorectomy, cortical tissue preparation, cryopreservation, and subsequent reimplantation, with the possibility of preserving not only fertility but also endocrine function and natural pubertal development. However, ovarian tissue in Turner syndrome frequently demonstrates poor follicular morphology and reduced reserve, and significant limitations remain, including premature follicular depletion, technical challenges in tissue processing, suboptimal revascularization after transplantation, and uncertain functional restoration. Psychological and ethical considerations further complicate decision-making, particularly in young patients. Prospective studies such as Turner Fertility support procedural feasibility, yet live birth outcomes remain rare. Overall, OTC may represent a meaningful fertility preservation option in carefully selected individuals with Turner syndrome, but current evidence is limited and individualized, multidisciplinary counselling is essential to align interventions with realistic expectations.
2026-05-25 | Live birth after oocyte donation in women with Turner syndrome compared with other causes of premature ovarian insufficiency: a retrospective cohort study.
To compare live birth rates after in vitro fertilization (IVF) with oocyte donation between women with Turner syndrome and women with premature ovarian insufficiency (POI) of other etiologies and to evaluate the relationships between uterine volume, duration of hormone replacement therapy (HRT), and obstetric outcomes. This retrospective cohort study included 97 women with POI undergoing IVF with oocyte donation at a university-affiliated tertiary care center between 2007 and 2023, including 30 women with Turner syndrome and 67 with POI of other etiologies. Artificial endometrial preparation cycles were used for all recipients. Uterine volume was measured by transvaginal ultrasound prior to the first embryo transfer. Primary outcome was live birth per embryo transfer. Secondary outcomes included live birth according to embryo transfer rank, associations between uterine volume and obstetric or neonatal outcomes, and the relationship between uterine volume and duration of prior HRT. A total of 245 embryo transfers were performed. Live birth rates per embryo transfer were comparable between women with Turner syndrome and those with other POI etiologies (29% vs. 27%). However, women with Turner syndrome had a significantly lower probability of achieving live birth at the first embryo transfer (adjusted odds ratio [OR] 0.09; 95% confidence interval [CI] 0.01-0.64), whereas no significant difference was observed after three or more transfers. Median uterine volume prior to IVF did not differ significantly between groups, despite a substantially longer duration of prior HRT in women with Turner syndrome (15.5 vs. 3.0 years). No significant association was observed between uterine volume and duration of HRT in either group. Among singleton pregnancies, decreasing uterine volume was associated with increased risks of preeclampsia, intrauterine growth restriction, non-cephalic presentation, and adverse neonatal outcomes. Women with Turner syndrome achieve live birth rates after IVF with oocyte donation comparable to those of women with other POI etiologies, although more embryo transfer attempts may be required. No clear association between uterine volume and duration of HRT was observed. However, decreasing uterine volume was associated with adverse obstetric outcomes, highlighting the importance of early hormonal management and careful obstetric surveillance in this population.
2026-04-15 | Successful Kidney Transplantation in Turner Syndrome: A Case for Feasibility and Favorable Outcomes.
Turner syndrome (TS) leads to various abnormalities, including renal malformations that can progress to end-stage renal disease (ESRD). Although rarely performed in patients with TS, renal transplantation offers significant benefits over dialysis. We report the case of a 34-year-old female with TS and ESRD who underwent a successful living-donor kidney transplantation. Preoperative imaging revealed atrophic, malformed native kidneys located entirely in the pelvic region. A suitable graft bed was meticulously created in the right iliac fossa without the need for native nephrectomy. At the 9-month postoperative follow-up, the patient demonstrated excellent and stable graft function. This case highlights the feasibility of kidney transplantation in patients with TS and underscores the importance of careful preoperative planning and a multidisciplinary approach to overcome unique anatomical challenges.
other
2024-02-25 | System biology approach to delineate expressional difference in the blood mononuclear cells between healthy and Turner syndrome individuals
Abstract Background Turner syndrome (TS) is a rare disorder associated either with complete or partial loss of one X chromosome in women. The information on the genotype–phenotype relationship in TS is inadequate. Comparing the healthy and Turner syndrome patients may help elucidate the mechanisms involved in TS pathophysiology. Gene expression differences between healthy and individuals with Turner syndrome were characterized using the systems-biology approach of weighted gene coexpression network analysis (WGCNA) on 182 microarray peripheral mononuclear blood samples (PBMC). Results The coexpression networks of healthy and TS had scale-free topology that ensures network robustness. In the process, five modules were preserved between healthy and TS, which carry several genes common in each module. Two of them, SMCHD1 and PGK1, have already been reported to be involved in TS. Previously reported genes of TS, specifically, PTPN22, RPS4X, CSF2RA, and TIMP1, were missing in their respective modules. Dysfunction, differential expression, or absence of these genes could lead to a progressive disruption of molecular pathways leading to the pathophysiology of TS. Indeed, we observed a significant difference in the functions of these modules when compared within and across the healthy and TS samples. We identified four clusters in the PPI network constructed from the top 15 KME enriched in significant functions. Conclusion Overall, our work highlights the potential molecular functions, pathways, and molecular targets of TS that can be exploited therapeutically in the human healthcare system.
2021-09-08 | Reproductive outcomes after preimplantation genetic testing in mosaic Turner syndrome: a retrospective cohort study of 100 cycles.
The purpose of this study is to explore the reproductive outcomes of women with Turner syndrome (TS) in preimplantation genetic testing (PGT) cycles. A retrospective study of 100 controlled ovarian stimulating cycles, 68 TS (sixty-four mosaic Turner syndrome (MTS) and four pure Turner syndrome (PTS)) women underwent PGT was conducted from 2013 to 2018. Embryo X chromosome abnormal rates of TS women were significantly higher than women with normal karyotype (7.04 vs 1.61%, P<0.01). Cumulative live birth rates (CLBR) after PGT-NGS treatment were lower in TS than control (31.15 vs 45.59%, P<0.05). Clinical pregnancy rates per transfer (CPR), miscarriage rates (MR) and live birth rates per transfer (LBR) remained comparable between TS and control group. Reproductive outcomes (X chromosome abnormal rates, CPR, MR, LBR and CLBR) among low (<10%), medium (10-50%) and high (>50%) level 45,X mosaicism groups were not statistically different. To avoid high risk of embryo X chromosome abnormalities, prenatal or preimplantation genetic testing should be recommended to mosaic or pure TS patients.
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Drug Discovery Landscape
8 orphan drug designations for Turner syndrome, including 4 approved therapies.
8 orphan drug designations for Turner syndrome, including 4 approved therapies.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
vosoritide | peptides | FDA | 2025-07-11 | — | BioMarin Pharmaceutical Inc. |
estradiol Gel | small molecules | FDA | 2006-10-31 | — | Ascend Therapeutics US, LLC |
Oxandrolone | small molecules | FDA | 1990-07-05 | — | Bio-Technology General Corp. |
Somatropin [Humatrope] | peptides | FDA | 1990-05-08 | 1996-12-30 | Eli Lilly and Company |
Somatropin for injection [Nutropin] | peptides | FDA | 1989-03-23 | 1996-12-30 | Genentech, Inc. |
Ethinyl Estradiol, USP | small molecules | FDA | 1988-06-22 | — | Bio-Technology General Corp. |
somapacitan-beco [Sogroya] | proteins | FDA | 1987-07-10 | 2023-04-28 | Novo Nordisk Pharmaceuticals |
Somatropin (rDNA origin) injection [Norditropin] | peptides | FDA | 1987-07-10 | 2000-06-20 | Novo Nordisk Pharmaceuticals |
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