Ann Pediatr Endocrinol Metab.  2017 Dec;22(4):226-230. 10.6065/apem.2017.22.4.226.

Diagnostic and therapeutic considerations in Turner syndrome

• Yang S

• KMID: 2400778
• DOI: http://doi.org/10.6065/apem.2017.22.4.226

Abstract

Newly developed genetic techniques can reveal mosaicism in individuals diagnosed with monosomy X. Noninvasive prenatal diagnosis using maternal blood can detect most fetuses with X chromosome abnormalities. Low-dose and ultralow-dose estrogen replacement therapy can achieve a more physiological endocrine milieu. However, many complicated and controversial issues with such treatment remain. Therefore, lifetime observation, long-term studies of health problems, and optimal therapeutic plans are needed for women with Turner syndrome. In this review, we discuss several diagnostic trials using recently developed genetic techniques and studies of physiological hormone replacement treatment over the last 5 years.

Keyword

Turner syndrome; Diagnosis; Hormone replacement therapy

MeSH Terms

Diagnosis
Estrogen Replacement Therapy
Female
Fetus
Genetic Techniques
Hormone Replacement Therapy
Humans
Mosaicism
Prenatal Diagnosis
Turner Syndrome*
X Chromosome

Reference

References

1. Turner HH. A syndrome of infantilism, congenital webbed neck, and cubitus valus. Endocrinology. 1938; 23:566–74.

2. Ford CE, Jones KW, Polani PE, De Almeida JC, Briggs JH. A sex-chromosome anomaly in a case of gonadal dysgenesis (Turner's syndrome). Lancet. 1959; 1:711–3.

3. Lemli L, Smith DW. The XO syndrome. A study of the differentiated phenotype in 25 patients. J Pediatr. 1963; 63:577–88.

4. Levitsky LL, Luria AH, Hayes FJ, Lin AE. Turner syndrome: update on biology and management across the life span. Curr Opin Endocrinol Diabetes Obes. 2015; 22:65–72.

5. Mohamed S, Roche EF, Hoey HM. Mode of initial presentation and chromosomal abnormalities in Irish patients with Turner syndrome: a single-centre experience. J Pediatr Endocrinol Metab. 2015; 28:1215–8.

6. Wonkam A, Veigne SW, Abass A, Ngo Um S, Noubiap JJ, Mbanya JC, et al. Features of Turner syndrome among a group of Cameroonian patients. Int J Gynaecol Obstet. 2015; 129:264–6.

7. Miguel-Neto J, Carvalho AB, Marques-de-Faria AP, Guerra- Júnior G, Maciel-Guerra AT. New approach to phenotypic variability and karyotype-phenotype correlation in Turner syndrome. J Pediatr Endocrinol Metab. 2016; 29:475–9.

8. Sari E, Bereket A, Yeşilkaya E, Baş F, Bundak R, Aydın BK, et al. Anthropometric findings from birth to adulthood and their relation with karyotpye distribution in Turkish girls with Turner syndrome. Am J Med Genet A. 2016; 170A:942–8.

9. Saari A, Sankilampi U, Hannila ML, Saha MT, Mäkitie O, Dunkel L. Screening of turner syndrome with novel auxological criteria facilitates early diagnosis. J Clin Endocrinol Metab. 2012; 97:E2125–32.

10. Mercer CL, Lachlan K, Karcanias A, Affara N, Huang S, Jacobs PA, et al. Detailed clinical and molecular study of 20 females with Xq deletions with special reference to menstruation and fertility. Eur J Med Genet. 2013; 56:1–6.

11. Mazloom AR, Džakula Ž, Oeth P, Wang H, Jensen T, Tynan J, et al. Noninvasive prenatal detection of sex chromosomal aneuploidies by sequencing circulating cell-free DNA from maternal plasma. Prenat Diagn. 2013; 33:591–7.

12. Liang D, Lv W, Wang H, Xu L, Liu J, Li H, et al. Non-invasive prenatal testing of fetal whole chromosome aneuploidy by massively parallel sequencing. Prenat Diagn. 2013; 33:409–15.

13. Castronovo C, Rossetti R, Rusconi D, Recalcati MP, Cacciatore C, Beccaria E, et al. Gene dosage as a relevant mechanism contributing to the determination of ovarian function in Turner syndrome. Hum Reprod. 2014; 29:368–79.

14. Corrêa SC, Rocha MN, Richeti F, Kochi C, Silva E Lima LA, Magalhães M, et al. Neonatal detection of Turner syndrome by real-time PCR gene quantification of the ARSE and MAGEH1 genes. Genet Mol Res. 2014; 13:9068–76.

15. Prakash S, Guo D, Maslen CL, Silberbach M, Milewicz D, Bondy CA, et al. Single-nucleotide polymorphism array genotyping is equivalent to metaphase cytogenetics for diagnosis of Turner syndrome. Genet Med. 2014; 16:53–9.

16. Hook EB, Warburton D. Turner syndrome revisited: review of new data supports the hypothesis that all viable 45,X cases are cryptic mosaics with a rescue cell line, implying an origin by mitotic loss. Hum Genet. 2014; 133:417–24.

17. Stanescu DE, Gruccio D. 50 Years ago in The Journal of Pediatrics: the XO syndrome: a study of the differential phenotype in 25 patients. J Pediatr. 2013; 163:1044.

18. Blum WF, Ross JL, Zimmermann AG, Quigley CA, Child CJ, Kalifa G, et al. GH treatment to final height produces similar height gains in patients with SHOX deficiency and Turner syndrome: results of a multicenter trial. J Clin Endocrinol Metab. 2013; 98:E1383–92.

19. Wasniewska M, Aversa T, Mazzanti L, Guarneri MP, Matarazzo P, De Luca F, et al. Adult height in girls with Turner syndrome treated from before 6 years of age with a fixed per kilogram GH dose. Eur J Endocrinol. 2013; 169:439–43.

20. Legro RS. Turner syndrome: new insights into an old disorder. Fertil Steril. 2012; 98:773–4.

21. Lyon AJ, Preece MA, Grant DB. Growth curve for girls with Turner syndrome. Arch Dis Child. 1985; 60:932–5.

22. Saari A, Sankilampi U, Dunkel L. Multiethnic WHO growth charts may not be optimal in the screening of disorders affecting height: Turner syndrome as a model. JAMA Pediatr. 2013; 167:194–5.

23. Bertapelli F, Barros-Filho Ade A, Antonio MÂ, Barbeta CJ, de Lemos-Marini SH, Guerra-Junior G. Growth curves for girls with Turner syndrome. Biomed Res Int. 2014; 2014:687978.

24. Clement-Jones M, Schiller S, Rao E, Blaschke RJ, Zuniga A, Zeller R, et al. The short stature homeobox gene SHOX is involved in skeletal abnormalities in Turner syndrome. Hum Mol Genet. 2000; 9:695–702.

25. Fiot E, Zenaty D, Boizeau P, Haigneré J, Dos Santos S, Léger J, et al. X-chromosome gene dosage as a determinant of impaired pre and postnatal growth and adult height in Turner syndrome. Eur J Endocrinol. 2016; 174:281–8.

26. Malaquias AC, Scalco RC, Fontenele EG, Costalonga EF, Baldin AD, Braz AF, et al. The sitting height/height ratio for age in healthy and short individuals and its potential role in selecting short children for SHOX analysis. Horm Res Paediatr. 2013; 80:449–56.

27. Tai S, Tanaka T, Hasegawa T, Ozono K, Tanaka H, Kanzaki S, et al. An observational study of the effectiveness and safety of growth hormone (Humatrope(^®)) treatment in Japanese children with growth hormone deficiency or Turner syndrome. Endocr J. 2013; 60:57–64.

28. Bettendorf M, Inta IM, Doerr HG, Hauffa BP, Mehls O, Ranke MB. Height gain in Ullrich-Turner syndrome after early and late growth hormone treatment start: results from a large retrospective German study and potential basis for an individualized treatment approach. Horm Res Paediatr. 2013; 80:356–62.

29. Clayton P, Chatelain P, Tatò L, Yoo HW, Ambler GR, Belgorosky A, et al. A pharmacogenomic approach to the treatment of children with GH deficiency or Turner syndrome. Eur J Endocrinol. 2013; 169:277–89.

30. Stevens A, Murray P, Wojcik J, Raelson J, Koledova E, Chatelain P, et al. Validating genetic markers of response to recombinant human growth hormone in children with growth hormone deficiency and Turner syndrome: the PREDICT validation study. Eur J Endocrinol. 2016; 175:633–43.

31. Braz AF, Costalonga EF, Trarbach EB, Scalco RC, Malaquias AC, Guerra-Junior G, et al. Genetic predictors of long-term response to growth hormone (GH) therapy in children with GH deficiency and Turner syndrome: the influence of a SOCS2 polymorphism. J Clin Endocrinol Metab. 2014; 99:E1808–13.

32. Schrier L, de Kam ML, McKinnon R, Che Bakri A, Oostdijk W, Sas TC, et al. Comparison of body surface area versus weight-based growth hormone dosing for girls with Turner syndrome. Horm Res Paediatr. 2014; 81:319–30.

33. Juloski J, Dumančić J, Šćepan I, Lauc T, Milašin J, Kaić Z, et al. Growth hormone positive effects on craniofacial complex in Turner syndrome. Arch Oral Biol. 2016; 71:10–5.

34. Soares MQ, Mendonca EF. Lichen planus-like drug reaction associated with recombinant human growth hormone therapy in a child patient with Turner syndrome. Dermatol Online J. 2016; Mar. 16. 22(3):pii: 13030/qt4k61f5jn.

35. Freriks K, Sas TC, Traas MA, Netea-Maier RT, den Heijer M, Hermus AR, et al. Long-term effects of previous oxandrolone treatment in adult women with Turner syndrome. Eur J Endocrinol. 2012; 168:91–9.

36. Sas TC, Gault EJ, Bardsley MZ, Menke LA, Freriks K, Perry RJ, et al. Safety and efficacy of oxandrolone in growth hormone-treated girls with Turner syndrome: evidence from recent studies and recommendations for use. Horm Res Paediatr. 2014; 81:289–97.

37. Xiong H, Chen HS, Du ML, Li YH, Ma HM, Su Z, et al. Therapeutic effects of growth hormone combined with low-dose stanozolol on growth velocity and final height of girls with Turner syndrome. Clin Endocrinol (Oxf ). 2015; 83:223–8.

38. Menke LA, Sas TC, de Muinck Keizer-Schrama SM, Zandwijken GR, de Ridder MA, Odink RJ, et al. Efficacy and safety of oxandrolone in growth hormone-treated girls with turner syndrome. J Clin Endocrinol Metab. 2010; 95:1151–60.

39. Visser JA, Hokken-Koelega AC, Zandwijken GR, Limacher A, Ranke MB, Flück CE. Anti-Müllerian hormone levels in girls and adolescents with Turner syndrome are related to karyotype, pubertal development and growth hormone treatment. Hum Reprod. 2013; 28:1899–907.

40. Ankarberg-Lindgren C, Kriström B, Norjavaara E. Physiological estrogen replacement therapy for puberty induction in girls: a clinical observational study. Horm Res Paediatr. 2014; 81:239–44.

41. Quigley CA, Wan X, Garg S, Kowal K, Cutler GB Jr, Ross JL. Effects of low-dose estrogen replacement during childhood on pubertal development and gonadotropin concentrations in patients with Turner syndrome: results of a randomized, double-blind, placebo-controlled clinical trial. J Clin Endocrinol Metab. 2014; 99:E1754–64.

42. 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 Endocrinol. 2017; 177:G1–70.

43. Torres-Santiago L, Mericq V, Taboada M, Unanue N, Klein KO, Singh R, et al. Metabolic effects of oral versus transdermal 17β-estradiol (E₂): a randomized clinical trial in girls with Turner syndrome. J Clin Endocrinol Metab. 2013; 98:2716–24.

44. Sweetland S, Beral V, Balkwill A, Liu B, Benson VS, Canonico M, et al. Venous thromboembolism risk in relation to use of different types of postmenopausal hormone therapy in a large prospective study. J Thromb Haemost. 2012; 10:2277–86.

45. Labarta JI, Moreno ML, López-Siguero JP, Luzuriaga C, Rica I, Sánchez-del Pozo J, et al. Individualised vs fixed dose of oral 17β-oestradiol for induction of puberty in girls with Turner syndrome: an open-randomised parallel trial. Eur J Endocrinol. 2012; 167:523–9.

46. Cleemann L, Holm K, Kobbernagel H, Kristensen B, Skouby SO, Jensen AK, et al. Dosage of estradiol, bone and body composition in Turner syndrome: a 5-year randomized controlled clinical trial. Eur J Endocrinol. 2017; 176:233–42.

47. Carel JC, Elie C, Ecosse E, Tauber M, Léger J, Cabrol S, et al. Self-esteem and social adjustment in young women with Turner syndrome--influence of pubertal management and sexuality: population-based cohort study. J Clin Endocrinol Metab. 2006; 91:2972–9.

48. Rosenfield RL, DiMeglio LA, Mauras N, Ross J, Shaw ND, Greeley SA, et al. Commentary: launch of a quality improvement network for evidence-based management of uncommon pediatric endocrine disorders: Turner syndrome as a prototype. J Clin Endocrinol Metab. 2015; 100:1234–6.

49. Gravholt CH, Juul S, Naeraa RW, Hansen J. Morbidity in Turner syndrome. J Clin Epidemiol. 1998; 51:147–58.

50. Hasle H, Olsen JH, Nielsen J, Hansen J, Friedrich U, Tommerup N. Occurrence of cancer in women with Turner syndrome. Br J Cancer. 1996; 73:1156–9.

51. Bannink EM, Raat H, Mulder PG, de Muinck Keizer- Schrama SM. Quality of life after growth hormone therapy and induced puberty in women with Turner syndrome. J Pediatr. 2006; 148:95–101.