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:
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.
2026-07-02 | 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.
2026-06-29 | 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.
2026-06-26 | 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.
2026-06-18 | 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.
2026-08-17 | 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.
2026-07-02 | 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.
2026-06-29 | 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.
2026-06-26 | 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.
2026-06-18 | 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.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
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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