Turner syndrome: results of the first Tunisian study group on Turner syndrome (TuSGOT)
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Leila Essaddam
,
Ons Zitouni
Abstract
Objectives
Early diagnosis in Turner syndrome is desirable to optimize growth and puberty and yet, it is often made late. Here, we aim to identify age at diagnosis, clinical features at presentation and potential strategies to improve the care of TS girls.
Methods
Retrospective study, including patients from 14 care centers across Tunisia including neonatal and pediatric care units, adult endocrinology and genetics departments.
Results
We identified 175 patients with TS, karyotype showing 45, xmonosomy in 83(47.4 %) with mosaicism in 37(20 %). Mean ± SD, median (range) age at diagnosis available in 173 patients was 13 ± 9.2,12 (birth-48) years. The diagnosis was antenatal in 4(2.3 %), from birth-2 years in 14 (8 %)with lymphoedema (8)and dysmorphic features (9),2–12 years in 53 (35.5 %) including 35 with short stature, 13–18 years in 43(28.8 %) with short stature(28) and delayed puberty(14) and 35(23.5 %) after 18 years, related to ovarian insufficiency (20) and short stature (11). The associated malformations were cardiac in 14 (12.8 %), renal in 22 (19.6 %). A total of 56 girls (32 %) had proven gonadal dysgenesis and 13 (7 %) had otological problems. Parental height was available in 71 girls (40 %) of whom 59 were below the lower end of parental target range (LTR) (83 %).
Conclusions
This first Tunisian multicenter study, the first African of its kind, reveals that more than half of Turner syndrome cases are diagnosed after the age of 12 years. Subsequently, national strategies for an earlier TS diagnosis are needed such as measuring and plotting parental heights as well as introducing a systematic height screening at 5 years in Tunisia with a view to carrying out a re-audit in five years’ time.
Acknowledgments
The authors gratefully acknowledge Dr Ahlem Gzara, Director of the Tunisian Basic Health Care Center (Tunisian Health Ministry) for all the valuable information she provided us regarding Tunisian national programs. The authors also gratefully acknowledge Dr Meriem Jones for her careful review, valuable assistance and helpful suggestions.
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Research funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.
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Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Competing interests: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of this work.
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Informed consent: Informed consent was obtained from all individuals included in this study.
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Ethical approval: The local Institutional Review Board deemed the study exempt from review.
References
1. Gravholt, CH, Andersen, NH, Conway, GS, Dekkers, OM, Geffner, ME, Klein, KO, et al.. Clinical practice guidelines for the care of girls and women with turner syndrome: proceedings from the 2016 cincinnati international turner syndrome meeting. Eur J Epidemiol 2017;177:G1–70. https://doi.org/10.1530/EJE-17-0430.10.1530/EJE-17-0430Search in Google Scholar PubMed
2. Bondy, CA. Care of girls and women with Turner syndrome: a guideline of the Turner syndrome study group. J Clin Endocrinol Metab 2007;92:10–25. https://doi.org/10.1210/jc.2006-1374.Search in Google Scholar PubMed
3. Lee, MC, Conway, GS. Turner’s syndrome: challenges of late diagnosis. Lancet Diabetes Endocrinol 2014;2:333–8. https://doi.org/10.1016/S2213-8587(13)70153-0.10.1016/S2213-8587(13)70153-0Search in Google Scholar PubMed
4. https://www.who.int/tools/child-growth-standards/standards/length-height-for-age.Search in Google Scholar
5. https://apkgk.com/fr/appinventor.ai_dlmetzger58.AnthroCalc.Search in Google Scholar
6. Cole, TJ, Bellizi, MC, Flegal, KM, Dietz, WH. Establishing a standard definition for child overweight and obesity worldwide: international survey. Brit Med J 2000;320:1240–5. https://doi.org/10.1136/bmj.320.7244.1240.Search in Google Scholar PubMed PubMed Central
7. Elleuch, M, Mnif Feki, M, Kammoun, M, Charfi, N, Rekik, N, Bouraoui, A, et al.. Descriptive analyses of Turner syndrome: 49 cases in Tunisia. Ann Endocrinol 2010;71:111–6. https://doi.org/10.1016/j.ando.2009.12.013.10.1016/j.ando.2009.12.013Search in Google Scholar PubMed
8. Gravholt, CH. Epidemiological, endocrine and metabolic features in turner syndrome. Eur J Epidemiol 2004;156:657–87. https://doi.org/10.1530/eje.0.1510657.10.1530/eje.0.1510657Search in Google Scholar PubMed
9. Stochholm, K, Juul, S, Juel, K, Weis Naeraa, R, Gravholt, CH. Prevalence, incidence, diagnostic delay, and mortality in turner syndrome. J Clin Endocrinol Metab 2006;91:3897–902. https://doi.org/10.1210/jc.2006-0558.Search in Google Scholar PubMed
10. Kallali, W, Messiaen, C, Saidi, R, Lessim, S, Viaud, M, Dulon, J, et al.. Age at diagnosis in patients with chronic congenital endocrine conditions: a regional cohort study from a reference center for rare diseases. Orphanet J Rare Dis 2021;16:469. https://doi.org/10.1186/s13023-021-02099-3.Search in Google Scholar PubMed PubMed Central
11. Gunther, DF, Eugster, E, Zagar, AJ, Bryant, CG, Davenport, ML, Quigley, CA. Ascertainment bias in turner syndrome: new insights from girls who were diagnosed incidentally in prenatal life. Pediatrics 2004;114:640–4. https://doi.org/10.1542/peds.2003-1122-L.Search in Google Scholar PubMed
12. Sävendahl, L, Davenport, ML. Delayed diagnoses of turner’s syndrome: proposed guidelines for change. J Pediatr 2000;137:455–9. https://doi.org/10.1067/mpd.2000.107390.10.1067/mpd.2000.107390Search in Google Scholar PubMed
13. Wong, SC, Burgess, T, Cheung, M, Zacharin, M. The prevalence of turner syndrome in girls presenting with coarctation of the aorta. J Pediatr 2014;164:259–63. https://doi.org/10.1016/j.jpeds.2013.09.031.Search in Google Scholar PubMed
14. Ouarezki, Y, Cizmecioglu, FM, Mansour, C, Huw Jones, J, Gault, EJ, Mason, A, et al.. Measured parental height in Turner syndrome—a valuable but underused diagnostic tool. Eur J Pediatr 2018;177:171–9. https://doi.org/10.1007/s00431-017-3045-2.Search in Google Scholar PubMed PubMed Central
15. Programme National de Vaccination. Manuel à l’usage des professionnels de la santé. Tunisian Health Ministry. Tunisia: Tunisian Basic Health Care Center and Unicef; 2016. http://www.santetunisie.rns.tn/fr/toutes-les-actualites/779-manuel-du-programme-national-de-vaccination.Search in Google Scholar
16. Unicef. Tunisie, rapport national sur les enfants non scolarisés. Unicef 2014:124.Search in Google Scholar
17. Management procedures for school and university medicine. Volume 2. Tunisian health ministry. Department of school and university medicine. 1998; 57.Search in Google Scholar
18. Batch, J. Turner syndrome in childhood and adolescence. Best Pract Res Clin Endocrinol Metabol 2002;16:465–82. https://doi.org/10.1053/beem.2002.0217.10.1053/beem.2002.0217Search in Google Scholar PubMed
19. Weiss, L. Additional evidence of gradual loss of germ cells in the pathogenesis of streak ovaries in Turner’s syndrome. J Med Genet 1971;8:540–4. https://doi.org/10.1136/jmg.8.4.540.10.1136/jmg.8.4.540Search in Google Scholar PubMed PubMed Central
20. Silberbach, M, Roos-Hesselink, JW, Andersen, NH, Braverman, AC, Brown, N, Collins, RT, et al.. Cardiovascular health in Turner syndrome: a scientific statement from the American Heart Association. Circ Genom Precis Med 2018;11:e000048. https://doi.org/10.1161/HCG.0000000000000048.10.1161/HCG.0000000000000048Search in Google Scholar PubMed
21. Carvalho, AB, Guerra Júnior, G, Baptista, MTM, Faria, APMde, Marini, SHVdeL, Guerra, ATM. Cardiovascular and renal anomalies in Turner syndrome. Rev Assoc Med Bras 2010;56:655–9. https://doi.org/10.1590/S0104-42302010000600012.10.1590/S0104-42302010000600012Search in Google Scholar PubMed
22. Bilge, I, Kayserili, H, Emre, S, Nayir, N, Sirin, A, Tukel, T, et al.. Frequency of renal malformations in Turner syndrome: analysis of 82 Turkish children. Pediatr Nephrol 2000;14:1111–4. https://doi.org/10.1007/s004670000315.10.1007/s004670000315Search in Google Scholar PubMed
23. Bispo, AVS, Dos Santos, LO, Burégio-Frota, P, Galdino, MB, Duarte, AR, Leal, GF, et al.. Effect of chromosome constitution variations on the expression of turner phenotype. Genet Mol Res 2013;12:4243–50. https://doi.org/10.4238/2013.March.13.13.10.4238/2013.March.13.13Search in Google Scholar PubMed
24. Bois, E, Nassar, M, Zenaty, D, Léger, J, Van Den Abbeele, T, Teissier, N. Otologic disorders in Turner syndrome. Eur Annal Otorhinolaryngol Head Neck Dis 2018;135:21–4. https://doi.org/10.1016/j.anorl.2017.08.006.10.1016/j.anorl.2017.08.006Search in Google Scholar PubMed
25. Kubba, H, Smyth, A, Wong, SC, Mason, A. Ear health and hearing surveillance in girls and women with Turner’s syndrome: recommendations from the turner’s syndrome support society. Clin Otolaryngol 2017;42:503–7. https://doi.org/10.1111/coa.12750.Search in Google Scholar PubMed
26. Tuke, MA, Ruth, KS, Wood, AR, Beaumont, RN, Tyrrell, J, Jones, JE, et al.. Mosaic turner syndrome shows reduced penetrance in an adult population study. Genet Med 2019;21:877–86. https://doi.org/10.1038/s41436-018-0271-6.10.1038/s41436-018-0271-6Search in Google Scholar PubMed PubMed Central
27. Gürsoy, S, Erçal, D. Turner syndrome and its variants. Pediatr Res 2017;4:171–5. https://doi.org/10.4274/jpr.35744.10.4274/jpr.35744Search in Google Scholar
28. Pimblett, AC, Rosa, CL, King, TFJ, Davies, MC, Conway, GS. The turner syndrome life course project: karyotype-phenotype analyses across the lifespan. Clin Endocrinol 2017;87:532–8. https://doi.org/10.1111/cen.13394.10.1111/cen.13394Search in Google Scholar PubMed
29. Fiot, E, Zénaty, D, Boizeau, P, Haignere, J, Santos, SD, Léger, J, et al.. Léger J on behalf of the french turner syndrome study group. X chromosome gene dosage as a determinant of congenital malformations and of age-related comorbidity risk in patients with turner syndrome, from childhood to early adulthood. Eur J Endocrinol 2019;180:397–406. https://doi.org/10.1530/EJE-18-0878.10.1530/EJE-18-0878Search in Google Scholar PubMed
30. Viuff, M, Skakkebæk, A, Nielsen, MM, Chang, S, Gravholt, CH. Epigenetics and genomics in Turner syndrome. Am J Med Genet C 2019:181125–132. https://doi.org/10.1002/ajmg.c.31683.10.1002/ajmg.c.31683Search in Google Scholar PubMed
31. Wolff, DJ, Van Dyke, DL, Powell, CM. A working group of the ACMG laboratory quality assurance committee. Laboratory guideline for turner syndrome. Genet Med 2010;12:52–5. https://doi.org/10.1097/GIM.0b013e3181c684b2.10.1097/GIM.0b013e3181c684b2Search in Google Scholar PubMed
32. Acosta, AM, Steinman, SE, White, KK. Orthopaedic manifestations in turner syndrome. J Am Acad Orthop Surg 2019;27:e1021–28. https://doi.org/10.5435/JAAOS-D-17-00796.10.5435/JAAOS-D-17-00796Search in Google Scholar PubMed
33. Sybert, VP, McCauley, E. Turner’s syndrome. N Engl J Med 2004;351:1227–38. https://doi.org/10.1056/NEJMra030360.10.1056/NEJMra030360Search in Google Scholar PubMed
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Articles in the same Issue
- Frontmatter
- Original Articles
- Impacts of the COVID-19 pandemic on the diagnosis of idiopathic central precocious puberty in pediatric females in New York City
- Genetic and clinical features of patients with intrahepatic cholestasis caused by citrin deficiency
- Unique clinical presentations and follow-up outcomes from experience with congenital disorders of glycosylation: PMM2-PGM1-DPAGT1-MPI-POMT2-B3GALNT2-DPM1-SRD5A3-CDG
- Executive function, behavioral problems, and insulin resistance in adolescents with obesity
- Utility of apolipoprotein ratio in predicting metabolic risk and microvascular complications in Indian children and young adults with type 1 diabetes mellitus
- Evaluation of 700 patients referred with a preliminary diagnosis of biotinidase deficiency by the national newborn metabolic screening program: a single-center experience
- Adiponectin–leptin ratio as a marker of cardio-metabolic risk in Indian children and youth with type 1 diabetes
- Dehydroepiandrosterone sulfate levels at 7 years old and cardio-metabolic factors at 10 and 13 years old – the generation XXI birth cohort
- Turner syndrome: results of the first Tunisian study group on Turner syndrome (TuSGOT)
- Adolescents who practice physical activity have adequate food choices, regardless of the level of somatic maturation and adiposity
- Case Reports
- ABCC8-related maturity-onset diabetes of the young: switching from insulin to sulphonylurea therapy: how long do we need for a good metabolic control?
- Coexistence of Graves’ disease with acute rheumatic fever treated as thyroid storm in young Thai patient
- GM1 gangliosidosis: patients with different phenotypic features and novel mutations
- Novel sonic hedgehog gene variant in a patient with hyponatremia, microsomia, and midline defects; phenotype description in association with a variant of unknown significance [c.755_757del p.(Phe252del)] and an approach to salt-wasting in SHH-related adrenal disorders
Articles in the same Issue
- Frontmatter
- Original Articles
- Impacts of the COVID-19 pandemic on the diagnosis of idiopathic central precocious puberty in pediatric females in New York City
- Genetic and clinical features of patients with intrahepatic cholestasis caused by citrin deficiency
- Unique clinical presentations and follow-up outcomes from experience with congenital disorders of glycosylation: PMM2-PGM1-DPAGT1-MPI-POMT2-B3GALNT2-DPM1-SRD5A3-CDG
- Executive function, behavioral problems, and insulin resistance in adolescents with obesity
- Utility of apolipoprotein ratio in predicting metabolic risk and microvascular complications in Indian children and young adults with type 1 diabetes mellitus
- Evaluation of 700 patients referred with a preliminary diagnosis of biotinidase deficiency by the national newborn metabolic screening program: a single-center experience
- Adiponectin–leptin ratio as a marker of cardio-metabolic risk in Indian children and youth with type 1 diabetes
- Dehydroepiandrosterone sulfate levels at 7 years old and cardio-metabolic factors at 10 and 13 years old – the generation XXI birth cohort
- Turner syndrome: results of the first Tunisian study group on Turner syndrome (TuSGOT)
- Adolescents who practice physical activity have adequate food choices, regardless of the level of somatic maturation and adiposity
- Case Reports
- ABCC8-related maturity-onset diabetes of the young: switching from insulin to sulphonylurea therapy: how long do we need for a good metabolic control?
- Coexistence of Graves’ disease with acute rheumatic fever treated as thyroid storm in young Thai patient
- GM1 gangliosidosis: patients with different phenotypic features and novel mutations
- Novel sonic hedgehog gene variant in a patient with hyponatremia, microsomia, and midline defects; phenotype description in association with a variant of unknown significance [c.755_757del p.(Phe252del)] and an approach to salt-wasting in SHH-related adrenal disorders
