Orphanet Journal of Rare Diseases | Cardiovascular Phenotypes of Children and Adolescents with Turner Syndrome

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This study analyzed clinical data from 107 Turner syndrome (TS) patients, revealing epidemiological characteristics of common cardiovascular diseases (e.g., bicuspid aortic valve, coarctation of the aorta) and exploring the potential of BMI-for-age Z-scores (BMIAZ) in predicting the risk of coarctation of the aorta. Additionally, the study emphasized the importance of early karyotyping in TS diagnosis.

 

Literature Overview

This article, titled 'Cardiovascular phenotypes of children and adolescents with Turner syndrome from a single-center cohort study', was published in the Orphanet Journal of Rare Diseases. It reviews and summarizes the cardiovascular phenotypic characteristics of Turner syndrome (TS) patients. The study reveals that TS patients frequently develop congenital or acquired cardiovascular diseases, such as bicuspid aortic valve (BAV) and coarctation of the aorta (CoA), with CoA being the main cause requiring surgical or interventional treatment. The article also highlights that the 45,X karyotype is associated with a higher risk of congenital heart disease (CHD), and BMIAZ can serve as a biomarker for predicting CoA.

Background Knowledge

Turner syndrome (Turner syndrome, TS) is a genetic disorder caused by complete or partial loss of the X chromosome, affecting approximately 25–50/100,000 female newborns. TS patients commonly exhibit short stature, cardiovascular abnormalities, skeletal developmental defects, and neurocognitive impairments. Cardiovascular disease is the leading cause of mortality in TS patients, with BAV, CoA, AD, and PAPVC being the most common phenotypes. Current clinical guidelines recommend cardiovascular magnetic resonance (CMR) for all TS patients at diagnosis, but compliance is low due to costs and anesthesia requirements. This study retrospectively analyzed clinical data from 107 TS patients to further explore the epidemiology, surgical interventions, and risk prediction factors of CHD, especially the role of BMIAZ in diagnosis. The study also found that the 45,X karyotype is associated with a higher CHD risk, and higher incidence rates of CoA and PAPVC in TS patients, highlighting the importance of karyotyping in cardiovascular screening. The research fills the gap in cardiovascular phenotypic data for Chinese TS populations and provides a foundation for early diagnosis and intervention strategies.

 

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Research Methods and Experimental Procedures

A total of 107 TS patients who underwent echocardiography at Shanghai Children's Medical Center between November 2019 and November 2024 were included in the study, excluding those with missing data (n=129). Data collected included height, weight, karyotype, cardiac imaging, and ECG information. Imaging modalities included CMR, CTA, and DSA. Continuous variables were compared using independent samples t-test and one-way ANOVA, categorical variables were analyzed using chi-square or Fisher's exact tests, and binary logistic regression was used for correlation analysis. The predictive value of BMIAZ for CoA was assessed using ROC curves.

Key Findings and Insights

• Approximately 32.7% (35/107) of TS patients had congenital heart disease (CHD), with BAV (11.2%), CoA (8.4%), and PLSVC (9.3%) being the most common.
• CHD was often diagnosed prior to TS confirmation, particularly evident in BAV and CoA cases.
• TS patients with CoA had significantly lower BMIAZ compared to those without CoA (-0.81 ± 1.17 vs. 0.61 ± 0.99; P = 0.003).
• BMIAZ showed an AUC of 0.825 (P = 0.004), with the optimal cutoff value at 0.115, yielding a sensitivity of 0.857 and specificity of 0.697.
• The 45,X karyotype was significantly associated with CHD (47.4% vs. 24.6%; P = 0.016), and also showed associations with BAV, PAPVC, and ARSA.
• CoA was the most common indication for surgical or interventional procedures among TS patients, accounting for 63.3% (7/11) of all interventions.
• QTc prolongation was not significantly increased in TS patients, and arrhythmias showed no strong association with karyotype.

Research Implications and Future Directions

This study underscores the importance of early cardiovascular screening in TS patients, especially those presenting with BAV, CoA, PLSVC, or PAPVC. It further supports the use of BMIAZ as a predictive biomarker for CoA, with a high AUC suggesting potential in clinical decision-making. Future studies should involve larger sample sizes and multi-center collaborations to validate phenotypic differences across populations with varying karyotypes. Additionally, further investigation into the mechanisms of arrhythmias and long-term follow-up data in TS patients is needed to optimize clinical management.

 

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Conclusion

This study systematically analyzed cardiovascular phenotypes in 107 TS patients, identifying a high prevalence of CHD, particularly BAV, CoA, and PLSVC. It further validated the significant association between CoA and lower BMIAZ, providing a clinical threshold for BMIAZ in predicting CoA. Moreover, the 45,X karyotype was found to be strongly linked with CHD, BAV, and PAPVC, highlighting its importance in TS diagnosis. The study recommends CMR or CT imaging at diagnosis for all TS patients, especially those with a 45,X karyotype, BMIAZ < 0.115, or echocardiographic evidence of CHD. Future research should focus on the genetic basis of cardiovascular disease in TS and the broader phenotypic distribution in diverse populations to enhance early diagnosis and personalized treatment strategies.

 

Hu, F., Wang, Y., Chen, Y., Chen, L., Wang, X. (2025). Cardiovascular phenotypes of children and adolescents with Turner syndrome from a single-center cohort study. Orphanet Journal of Rare Diseases.