Bicuspid Aortic Valve Disease in Turner Syndrome: A Meta-Analysis of Prevalence

Abstract

Turner syndrome patients partially or completely lack the X chromosome. 1 - 2500 female live births are affected. Clinical features include webbed neck, short stature, broad chest etc. Bicuspid aortic valve disease (BAV) occurs in more than 30% of Turner syndrome patients causing significant morbidity and mortality. We aimed to establish a more reliable estimate of the prevalence of BAV in Turner syndrome. PubMed, Embase and PsycINFO databases were searched until 2022. Review Manager (RevMan 5.4.1) and the JASP software (0.16.00) were used for meta-analysis. 15 studies with a total of 3189 patients were combined. The pooled prevalence of BAV in Turner syndrome was 22.0% (95% CI: 15.0% - 29.0%). Sub group analysis by 45, X0 karyotype and age had prevalence of 24.0% and 8% respectively. The studies had high heterogeneity and possible publication biases. In summary, the study established that the prevalence of BAV in Turner syndrome patients diagnosed by echocardiogram, CT and MRI scans, is 22.0%, and 24% in patients with true monosomy 45, X0 karyotypes. Routine BAV exam should pay particular attention to monosomy 45, X0 karyotype patients, and where possible, CT and MRI should always accompany echocardiography for BAV screening, especially for pediatrics.

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Thokerunga, E. , Ali, Y. and Ntege, C. (2022) Bicuspid Aortic Valve Disease in Turner Syndrome: A Meta-Analysis of Prevalence. International Journal of Clinical Medicine, 13, 276-286. doi: 10.4236/ijcm.2022.137023.

1. Introduction

Turner syndrome is a genetic anomaly in which an individual partially or completely lacks the X chromosome [1]. It occurs in about 1 - 2500 female live births [2], and physically presents with clinical features such as a webbed neck, short stature, cubitus valgus, a broad chest, gonadal dysgenesis, and late puberty [3]. Close to 50% of Turner syndrome patients develop congenitally or acquired cardiovascular complications causing significant morbidity and mortality [4], among them are aortic coarctation, elongated transverse aorta, partial anomalous pulmonary venous return, and bicuspid aortic valves [5].

Bicuspid aortic valve disease (BAV) is a congenital heart defect in which the aorta has only two instead of the usual three valve leaflets [6]. BAV is a clinical feature of more than 30% of Turner syndrome patients [7]. It’s often asymptomatic in the general population and only discovered on routine medical checkups [8]. However, in Turner syndrome, the co-occurrence of other heart defects such as aortic coarctation exacerbates the condition resulting in aortic dilation and dissection of the aorta which is fatal [9].

The close association between Turner syndrome and BAV warrants a regular cardiovascular assessment of all Turner syndrome patients to ensure early and prompt interventions, and so, knowing the prevalence of BAV in Turner syndrome patients facilitates planning this assessment process. Various studies have reported the prevalence of BAV in Turner syndrome, and one meta-analysis provided a summarized estimate, albeit with few studies combined and small sample size [10]. In this meta-analysis, we provide a more comprehensive and reliable pooled prevalence estimate of BAV in Turner syndrome and attempt to establish prevalence in sub populations of Turner syndrome such as the pure monosomy 45, X0 karyotypes and pediatric patients.

2. Materials and Methods

2.1. Search Strategies

Three reviewers independently searched PubMed, Embase, and PsycINFO databases for relevant studies on the prevalence of BAV in Turner syndrome patients. The customized search strategies for PubMed were #1. (“Prevalence” [MeSH Terms]) OR (“Occurrence” [All Fields]) OR (“Prevalence” [Title/ Abstract]) OR (“Presence of” [All Fields]), #2. (“Bicuspid aortic valve” [MeSH Terms]) OR (“Bicuspid aortic valve disease” [Title/Abstract]) OR (“BAV” [All Fields]) OR (“Bicuspid valve” [Title/Abstract]) OR (“Bicuspid aorta valve” [Title/Abstract]), #3. (“Turner syndrome patients” [MeSH Terms]) OR (“Turner syndrome” [Title/Abstract]) OR (“Turner disease” [Title/Abstract]) OR (“TS” [Title/Abstract]), #4. #1 and #2 and # 3, while those for Embase and PsycINFO were: #1. (Prevalence/exp) OR (Occurrence .ab,ti.) OR (prevalence.af.) OR (presence of .ab,ti.), #2. (Bicuspid aortic valve/exp) or (“Bicuspid aortic valve disease” .ab,ti.) OR (“Bicuspid aorta” .ab,ti.), #3. (Turner syndrome/exp) OR (Turner syndrome disorder .ab,ti.), #4. #1 and #2 and # 3.

The databases were searched in July 2021, then updated in December 2021 and February 2022. The studies were then exported into Endnote software (version 9) for cleaning, and duplicates removed. Studies from the initial search were rejected immediately if the title or abstract did not report prevalence or incidence of bicuspid aortic valve disease in Turner syndrome patients. Full texts were then extracted for the remaining articles and analyzed. Manual search of all the references of the full text articles were done. Disagreements that arose during the search were all settled by consensus. Extraction of information was carried out according to the Preferred reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines [11].

2.2. Inclusion and Exclusion Criteria

Relevant studies that were selected for inclusion had to meet the following criteria: 1) Assessed the prevalence of bicuspid aortic valve disease in patients with Turner syndrome; 2) BAV diagnosis was conducted using TTE or TEE or CT or MRI; 3) Had enough raw data to calculate prevalence of BAV in Turner syndrome if not already reported. Studies were excluded from the analysis if they were: case reports or case series, reviews or meta-analyses, conference abstracts or papers, did not assess the prevalence of bicuspid aortic valve disease in Turner syndrome patients, and was not published in a peer review journal.

2.3. Quality Assessment of the Studies

Three authors independently evaluated the methodological qualities of the selected studies using the Joanna Briggs Institute (JBI) critical appraisal checklist for analytical cross sectional studies [12]. Interrater reliability above 80% were considered acceptable, and all disagreements were resolved by consensus. The filled checklist is provided as supplementary materials 1. The JBI checklist assesses studies on nine critical areas that include: sample frame appropriateness, sampling technique, and sample size among others.

2.4. Data Extraction

A data extraction questionnaire was created and relevant data extracted from the included studies. Data extracted included: Name of first author, year of publication, country of the study, diagnostic tool for bicuspid aortic valve disease, summary of participants’ age, number of events (BAV), total number of participants, prevalence of BAV and its calculated standard error and Turner syndrome karyotypes.

2.5. Statistical Analysis

The prevalence of BAV disease was determined as number of BAV cases over total number of Turner syndrome patents x100. Standard Error (SE) was calculated for studies that did not report them, using the prevalence data and the formula: SE = Sqrt of p (1 − p)/n, while the 95% confidence interval (CI) = p ± 1.96 × SE; where, p = Prevalence. The data were combined using Review Manger (RevMan 5.4.1) and the JASP software (0.16.00). Heterogeneity was assessed using Chi-square test, and the I2 test. Random effect model was used to pool the results. Possible publication bias was assessed by visual inspection of a funnel plot and the Egger’s test.

3. Result

Preliminary searches yielded 901 records altogether. No additional records were found from other sources. 812 of the studies were from PubMed, 83 from Embase and 6 from PsycINFO databases. Following removal of duplicates, 778 studies were left and their titles and abstracts screened for eligibility. 749 studies were then excluded and eventually 29 qualified for full text screening. Here, 14 studies were omitted; 5 did not report prevalence of BAV in Turner syndrome patients and didn’t have the required raw data to manually do so, 7 were abstracts only or conference presentations and 2 were letters to the editor. Altogether, 15 studies [13] - [27] ranging from 2010 to 2020 and containing 3189 Turner syndrome patients were enrolled for meta-analysis (Table 1). The study selection and eligibility flowchart is presented in Figure 1. Among them 4 were conducted in the US, 2 from Turkey, 2 from the Netherlands, 2 from Poland and 1 each from France, Ukraine, France, Canada and Taiwan.

Table 1. Characteristics of included studies.

Figure 1. Study selection flowchart.

From among the included studies, the prevalence of Bicuspid Aortic Valve disease (BAV) among Turner syndrome patients was between 2.04% to 41.0%. The pooled prevalence after meta-analysis was 22.0% [95% CI: 15.0% - 29.0%], (Figure 2). Studies varied widely as indicated by the high level of heterogeneity, I2 = 97% (P < 0.00001). Possible publication bias was determined by visual inspection of a funnel plot (Figure 3), and an Egger’s test conducted (Table 2). Four studies determined the prevalence of BAV by Turner syndrome karyotype. Monosomy 45x karyotype had the most frequent cases of BAV compared to others. A subgroup analysis of the four studies conducted by Turner syndrome karyotype showed a pooled prevalence of 24.0% [95% CI: 9.0% - 39.0%] among the Monosomy 45x patients (Figure 4). Similarly, three studies explicitly studied BAV among children with Turner syndrome aged 0 to 18 years. Pooled prevalence in these studies was 8.0% [95% CI: 2% - 15%] (Figure 5).

4. Discussion

In this study, we have provided a summary estimate of the prevalence of Bicuspid aortic valve disease (BAV) in Turner syndrome patients. We have pooled published studies up to 2022, without any time constraints, as a result, our study had a combined total of 3189 patients, adequately powering the study. This is a comprehensive assessment of studies conducted on BAV in Turner syndrome patients, hence giving a more robust and reliable estimate of the prevalence of BAV in Turner syndrome. In addition, we were able to conduct subgroup analyses for age and Turner syndrome karyotypes to account for the heterogeneity that existed among the individual studies. Our pooled prevalence indicates that close to a quarter of Turner syndrome patients (22%) develop BAV, while the prevalence were 24.0% and 8% for 45, X0 karyotype, and pediatrics respectively.

This result is comparable to a similar study conducted by Li et al. [10], who found a prevalence of 23.7%. Unlike their study however, ours is more comprehensive and highly powered; with a sample size three times theirs. This makes our study more robust and reliable. Furthermore, unlike theirs, our study evaluated prevalence of BAV in Tuner syndrome patients with 45, X0 karyotype (being the most common karyotype), and among pediatrics, since BAV is a congenital disease.

Figure 2. Forest plot of the pooled prevalence of BAV in Turner syndrome patients.

Figure 3. Funnel plot indicting possible publication bias shown by the lack of symmetry.

Figure 4. Forest plot showing prevalence of BAV in true monosomy 45, X0 Turner syndrome patients.

Figure 5. Forest plot of prevalence of BAV in pediatric Turner syndrome patient.

Table 2. Regression test for Funnel plot asymmetry (“Egger’s test”).

The possible association between Turner syndrome and cardiovascular defects including BAV has been demonstrated by a number of studies [13] - [28], as a result, vasculopathy is often seen as one of the defining features of Turner syndrome [29]. Cardiovascular complications are of particular concern to Turner syndrome patients because factors that promote cardiovascular diseases such as obesity, hyperlipidemias, atherosclerosis etc. are also quite common among Turner syndrome patients [30]. Malformation of the aortic valve is manifested in changes to the way blood flows in the ascending aorta, and is one of the causes of aortic dilation and dissection [31]. Our findings—showing that close to 1 in 4 Turner syndrome patients had BAV—reinforces the 2016 recommendation by Gravholt et al. [28], that all Turner syndrome patients should be routinely examined for BAV. However, in the course of this routine examination, emphasis should be put on 45, X0 karyotype patients, since by our results, they seem to have a higher prevalence of BAV than the other karyotypes. Other cardiovascular defects associated with BAV and Turner syndrome that should be equally checked include; aortic coarctation, elongated transverse aorta, and partial anomalous pulmonary venous connection [21].

Despite the frequent presence of mosaicism among Turner syndrome karyotypes, true monosomy X having the 45, X0 still accounts for an estimated 40% - 50% of all cases [32]. In our analysis, the pooled prevalence of BAV among the 45X, X0 karyotype (24%) was just slightly above that of the general Turner syndrome population. This however, was an estimate from only four of the studies that had data for the association. We therefore think the true estimate could be much higher if more studies had data on this association. BAV is a congenital heart defect that is often asymptomatic in the general population, sometimes until adulthood [8]. This is not the case with Turner syndrome where the risk developing symptomatic BAV right from childhood is exacerbated by other associated cardiovascular complications. Our pooled prevalence of BAV in pediatric Turner syndrome patients was 8% from three studies. Much as echocardiography is the diagnostic tool of choice in BAV, it is not entirely sensitive enough and may miss cases especially in children. Bondy et al. and the Turner syndrome study group advised that Cardiac Magnetic Resonance Imaging (CMR) be done for all pediatric patients who can be imaged without sedation whose Echocardiogram results are negative [33]. Similar remarks form a study conducted specifically in pediatric subjects by Somerville et al., reaffirmed this suggestion as CMR was able to detect BAV cases that were missed by Echocardiogram [27].

Limitations

Being mostly retrospective cross sectional studies, we could not rule out potential biases among the individual studies. In fact both the funnel plot and Egger’s test conducted showed possible publication biases. Secondly, the studies were quite heterogeneous hence somehow affecting generalization of the result. Lastly, most of the studies did not evaluate BAV prevalence by Turner syndrome karyotype, and so the sub group analysis by karyotype should be interpreted with caution.

5. Conclusion

In summary, this study found that the prevalence of BAV in patients with Turner syndrome is 22% and that by karyotype, 24% of true monosomy 45, X0 develop BAV, while 8% of pediatric patients develop the complication. With a sample size of 3189, this is a more reliable estimate of the prevalence of BAV in Turner syndrome patients. Given that 1 in 4 Turner syndrome patient is likely to have BAV according to this result, and that true monosomy 45, X0 karyotypes seem to have a higher prevalence than the rest, particular attention should be put on patients with true monosomy 45, X0 karyotypes in the course of routine screening for BAV and other cardiovascular diseases in Turner syndrome patients. Lastly, where possible, CT and MRI should always accompany echocardiography for BAV screening, especially in pediatric patients.

Author Contributions

“Conceptualization: Erick Thokerunga; methodology: Erick Thokerunga; software: Erick Thokerunga; validation: Erick Thokerunga; formal analysis: Erick Thokerunga and Yahya-Abdullahi Ali; data curation: Yahya-Abdullahi Ali and Erick Thokerunga; writing-original draft preparation: Erick Thokerunga; writing-review and editing: Yahya-Abdullahi Ali and Christopher Ntege; supervision: Christopher Ntege; funding acquisition: Christopher Ntege. All authors have read and agreed to the published version of the manuscript”.

Acknowledgements

The authors acknowledge the immense contributions of Ms. Bena Binoga for the grammatical review and edit of this manuscript.

Conflicts of Interest

The authors declare no conflicts of interest regarding the publication of this paper.

References

[1] Huang, A.C., Olson, S.B. and Maslen, C.L. (2021) A Review of Recent Developments in Turner Syndrome Research. Journal of Cardiovascular Development and Disease, 8, Article 138.
https://doi.org/10.3390/jcdd8110138
[2] Cui, X., Cui, Y., Shi, L., Luan, J., Zhou, X. and Han, J. (2018) A Basic Understanding of Turner Syndrome: Incidence, Complications, Diagnosis, and Treatment. Intractable & Rare Diseases Research, 7, 223-238.
https://doi.org/10.5582/irdr.2017.01056
[3] National Institutes of Health (2021) What Are the Symptoms of Turner Syndrome?
https://www.nichd.nih.gov/health/topics/turner/conditioninfo/symptoms
[4] Silberbach, M., Roos-Hesselink, J.W., Andersen, N.H., Braverman, A.C., Brown, N., Collins, R.T., et al. (2018) Cardiovascular Health in Turner Syndrome: A Scientific Statement from the American Heart Association. Circulation: Genomic and Precision Medicine, 11, e000048.
https://doi.org/10.1161/HCG.0000000000000048
[5] Noad, R.L., Mcmanus, J., Wright, W., Mckeown, P.P. and Muir, A.R. (2013) Prevalence of Cardiac Abnormalities in the Turner Syndrome Population in Northern European Heart Journal, 34, Article No. P2109.
https://doi.org/10.1093/eurheartj/eht308.P2109
[6] Bravo-Jaimes, K. and Prakash, S.K. (2020) Genetics in Bicuspid Aortic Valve Disease: Where Are We? Progress in Cardiovascular Diseases, 63, 398-406.
https://doi.org/10.1016/j.pcad.2020.06.005
[7] Carlson, M. and Silberbach, M. (2009) Dissection of the Aorta in Turner Syndrome: Two Cases and Review of 85 Cases in the Literature. BMJ Case Reports, 2009.
https://doi.org/10.1136/bcr.06.2009.1998
[8] Mayo Clinic Staff (2022) Bicuspid Aortic Valve—Overview.
https://www.mayoclinic.org/diseases-conditions/bicuspid-aortic-valve/cdc-20385577
[9] Kriksciuniene, R., Ostrauskas, R. and Zilaitiene, B. (2015) Aortopathies in Turner Syndrome—New Strategies for Evaluation and Treatment. Endokrynologia Polska, 66, 58-65.
https://doi.org/10.5603/EP.2015.0010
[10] Li, P., Bačová, M., Dalla-Pozza, R., Alexander Haas, N. and Sebastian Oberhoffer, F. (2022) Prevalence of Bicuspid Aortic Valve in Turner Syndrome Patients Receiving Cardiac MRI and CT: A Meta-Analysis. Congenital Heart Disease, 17, 129-141.
https://doi.org/10.32604/CHD.2022.018300
[11] Page, M.J., McKenzie, J.E., Bossuyt, P.M., Boutron, I., Hoffmann, T.C., Mulrow, C.D., et al. (2021) The PRISMA 2020 Statement: An Updated Guideline for Reporting Systematic Reviews. BMJ, 372, Article No. n71.
https://doi.org/10.1136/bmj.n71
[12] Joanna Briggs Institute (2017) The Joanna Briggs Institute Critical Appraisal Tools for Use in JBI Systematic Reviews: Checklist for Analytical Cross Sectional Studies. Joanna Briggs Institute, Adelaide.
https://jbi.global/sites/default/files/2019-05/JBI_Critical_Appraisal-Checklist_for_Analytical_Cross_Sectional_Studies2017_0.pdf
[13] Chou, Y.-Y., Wang, C.-J., Lin, C.-H., Chung, H.-T. and Lo, F.-S. (2020) Association between Cardiovascular Anomalies and Karyotypes in Turner Syndrome Patients in Taiwan: A Local Cohort Study. Pediatrics & Neonatology, 61, 188-194.
https://doi.org/10.1016/j.pedneo.2019.10.001
[14] Donadille, B., Rousseau, A., Zenaty, D., Cabrol, S., Courtillot, C., Samara-Boustani, D., et al. (2012) Cardiovascular Findings and Management in Turner Syndrome: Insights from a French Cohort. European Journal of Endocrinology, 167, 517-522.
https://doi.org/10.1530/EJE-12-0434
[15] Olivieri, L.J., Baba, R.Y., Arai, A.E., Bandettini, W.P., Rosing, D.R., Bakalov, V., et al. (2013) Spectrum of Aortic Valve Abnormalities Associated with Aortic Dilation across Age Groups in Turner Syndrome. Circulation: Cardiovascular Imaging, 6, 1018-1023.
https://doi.org/10.1161/CIRCIMAGING.113.000526
[16] Yeşilkaya, E., Bereket, A., Darendeliler, F., Baş, F., Poyrazoğlu, Ş., Küçükemre Aydın, B., et al. (2015) Turner Syndrome and Associated Problems in Turkish Children: A Multicenter Study. Journal of Clinical Research in Pediatric Endocrinology, 7, 27-36.
https://doi.org/10.4274/jcrpe.1771
[17] Bondy, C., Bakalov, V.K., Cheng, C., Olivieri, L., Rosing, D.R. and Arai, A.E. (2013) Bicuspid Aortic Valve and Aortic Coarctation Are Linked to Deletion of the X Chromosome Short Arm in Turner Syndrome. Journal of Medical Genetics, 50, 662-625.
https://doi.org/10.1136/jmedgenet-2013-101720
[18] Klásková, E., Zapletalová, J., Kaprálová, S., Şnajderová, M., Lebl, J., Tüdös, Z., et al. (2017) Increased Prevalence of Bicuspid Aortic Valve in Turner Syndrome Links with Karyotype: The Crucial Importance of Detailed Cardiovascular Screening. Journal of Pediatric Endocrinology and Metabolism, 30, 319-325.
https://doi.org/10.1515/jpem-2016-0301
[19] Mondal, S., Bhattacharjee, R., Chowdhury, S. and Mukhopadhyay, S. (2021) Karyotype-Phenotype Correlation in Turner Syndrome at a Single Center in Eastern India. Indian Pediatrics, 58, 34-37.
https://doi.org/10.1007/s13312-021-2093-x
[20] Yetman, A.T., Starr, L., Sanmann, J., Wilde, M., Murray, M. and Cramer, J.W. (2018) Clinical and Echocardiographic Prevalence and Detection of Congenital and Acquired Cardiac Abnormalities in Girls and Women with the Turner Syndrome. American Journal of Cardiology, 122, 327-330.
https://www.ajconline.org/article/S0002-9149(18)30840-3/fulltext
[21] Kim, H.K., Gottliebson, W., Hor, K., Backeljauw, P., Gutmark-Little, I., Salisbury, S.R., et al. (2011) Cardiovascular Anomalies in Turner Syndrome: Spectrum, Prevalence, and Cardiac MRI Findings in a Pediatric and Young Adult Population. American Journal of Roentgenology, 196, 454-460.
https://doi.org/10.2214/AJR.10.4973
[22] Zelinska, N., Shevchenko, I. and Globa, E. (2018) Nationwide Study of Turner Syndrome in Ukrainian Children: Prevalence, Genetic Variants and Phenotypic Features. Journal of Clinical Research in Pediatric Endocrinology, 10, 256-263.
https://doi.org/10.4274/jcrpe.5119
[23] Yiğit, H., Önder, A., Özgür, S., Aycan, Z., Karademir, S. and Doğan, V. (2017) Cardiac MRI and 3D Contrast-Enhanced MR Angiography in Pediatric and Young Adult Patients with Turner Syndrome. Turkish Journal of Medical Sciences, 47, 127-133.
https://doi.org/10.3906/sag-1511-3
[24] Obara-Moszynska, M., Rajewska-Tabor, J., Rozmiarek, S., Karmelita-Katulska, K., Kociemba, A., Rabska-Pietrzak, B., et al. (2018) The Usefulness of Magnetic Resonance Imaging of the Cardiovascular System in the Diagnostic Work-Up of Patients with Turner Syndrome. Frontiers in Endocrinology, 9, Article No. 609.
https://doi.org/10.3389/fendo.2018.00609
[25] Duijnhouwer, A.L., Bons, L.R., Timmers, H.J.L.M., van Kimmenade, R.R.L., Snoeren, M., Timmermans, J., et al. (2019) Aortic Dilatation and Outcome in Women with Turner Syndrome. Heart, 105, 693-700.
https://doi.org/10.1136/heartjnl-2018-313716
[26] Bons, L.R., Duijnhouwer, A.L., Boccalini, S., van den Hoven, A.T., van der Vlugt, M.J., Chelu, R.G., et al. (2019) Intermodality Variation of Aortic Dimensions: How, Where and When to Measure the Ascending Aorta. International Journal of Cardiology, 276, 230-235.
https://doi.org/10.1016/j.ijcard.2018.08.067
[27] Somerville, S., Rosolowsky, E., Suntratonpipat, S., Girgis, R., Goot, B.H. and Tham, E.B. (2016) Cardiac Magnetic Resonance Imaging in Pediatric Turner Syndrome. The Journal of Pediatrics, 175, 111-115.e1.
https://doi.org/10.1016/j.jpeds.2016.04.080
[28] Gravholt, C.H., Andersen, N.H., Conway, G.S., Dekkers, O.M., Geffner, M.E., Klein, K.O., et al. (2017) Clinical Practice Guidelines for the Care of Girls and Women with Turner Syndrome: Proceedings from the 2016 Cincinnati International Turner Syndrome Meeting. European Journal of Endocrinology, 177, G1-G70.
https://doi.org/10.1530/EJE-17-0430
[29] Ostberg, J.E., Donald, A.E., Halcox, J.P.J., Storry, C., McCarthy, C. and Conway, G.S. (2005) Vasculopathy in Turner Syndrome: Arterial Dilatation and Intimal Thickening without Endothelial Dysfunction. The Journal of Clinical Endocrinology & Metabolism, 90, 5161-5166.
https://doi.org/10.1210/jc.2005-0677
[30] Oberhoffer, F.S., Abdul-Khaliq, H., Jung, A.-M., Rohrer, T.R. and Abd El Rahman, M. (2019) Two-Dimensional Speckle Tracking of the Abdominal Aorta: A Novel Approach to Evaluate Arterial Stiffness in Patients with Turner Syndrome. Cardiovascular Diagnosis and Therapy, 9, S228-S237.
https://doi.org/10.21037/cdt.2019.03.01
[31] Antequera-González, B., Martínez-Micaelo, N. and Alegret, J.M. (2020) Bicuspid Aortic Valve and Endothelial Dysfunction: Current Evidence and Potential Therapeutic Targets. Frontiers in Physiology, 11, Article No. 1015.
https://doi.org/10.3389/fphys.2020.01015
[32] Lin, A.E., Prakash, S.K., Andersen, N.H., Viuff, M.H., Levitsky, L.L., Rivera-Davila, M., et al. (2019) Recognition and Management of Adults with Turner Syndrome: From the Transition of Adolescence through the Senior Years. American Journal of Medical Genetics Part A, 179, 1987-2033.
https://doi.org/10.1002/ajmg.a.61310
[33] Bondy, C.A. (2007) Care of Girls and Women with Turner Syndrome: A Guideline of the Turner Syndrome Study Group. The Journal of Clinical Endocrinology & Metabolism, 92, 10-25.
https://doi.org/10.1210/jc.2006-1374

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