Turner Syndrome Diagnosis: challenges and implications
DOI:
https://doi.org/10.5902/2236583488238Keywords:
Turner Syndrome, Karyotype, Diagnosis, TherapyAbstract
Turner Syndrome (TS) is characterized by a total or partial monosomy of the X sex chromosome. There is a very large variability in phenotypic presentations, which makes its diagnosis a difficult task. Late age at diagnosis can compromise treatment results and have psychological impacts on patients with TS. Therefore, the objective of this study is to describe the age at diagnosis in TS and, when available, which clinical signs contributed to this diagnosis and their relationship with the karyotype, as well as the associated challenges and implications. This is a systematic review of the literature, carried out on PubMed, using the terms “Turner Syndrome”, “Delayed Diagnosis” and “Early Diagnosis”. Regarding eligibility criteria, original articles published in any year, in the English language, and which contained information regarding age at diagnosis of TS were included. Review articles, case reports or editorials, those published in a language other than English and those that did not respond to the research objective were excluded. 108 articles were identified and 21 were included after applying the inclusion and exclusion criteria. Only seven articles had the main objective of describing age at diagnosis and three of them presented this information in the title. Eight studies analyzed age at diagnosis among individuals with different karyotypes and reported an early age at diagnosis in 45,X patients. The diagnosis was predominantly made in childhood/adolescence due mainly to short stature. The issue of hormonal treatment was presented very succinctly, highlighting the interference of late diagnosis in its effectiveness. Obtaining an early diagnosis in TS is extremely relevant as it would allow such patients to undergo growth hormone therapy and sex hormone replacement at an appropriate age.
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References
Gravholt CH, Viuff MH, Brun S, Stochholm K, Andersen NH. Turner syndrome: mechanisms and management. Nat Rev Endocrinol. 2019;15(10):601-14. doi: 10.1038/s41574-019-0224-4.
Comissão Nacional De Incorporação De Tecnologias No Sistema Único De Saúde (Conitec). Protocolos Clínicos E Diretrizes Terapêuticas (Pcdt). Available From: Http://Conitec.Gov.Br/Index.Php/Protocolos-E-Diretrizes
Subramonian A, Horton J. Somatropin for Turner Syndrome: CADTH Health Technology Review [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2023 Aug. Report No.: RC1493.
Castro-Feijóo L, Rodríguez PC, Pérez RT, Meleiro JMI. GH de larga acción. Rev Esp Endocrinol Pediatr 2024;15,2.
Carvalho AB, Lemos-Marini SHV, Guerra-Junior G, Maciel-Guerra AT. Clinical and cytogenetic features of 516 patients with suspected Turner syndrome - a single-center experience. J Pediatr Endocrinol Metab. 2018;31(2):167-73. doi: 10.1515/jpem-2017-0273.
Carvalho AB, Guerra-Junior G, Baptista MT, Marques-de-Faria AP, Lemos-Marini SH, Maciel-Guerra AT. Turner syndrome: a pediatric diagnosis frequently made by non-pediatricians. J Pediatr (Rio J). 2010;86(2):121-5. doi: 10.2223/JPED.1985.
Nunes MR, Pereira TG, Correia HVD, Canabarro ST, Vanz AP, Zen PRG, et al. Clinical and cytogenetic characteristics of patients diagnosed with Turner syndrome in a clinical genetics service: cross-sectional retrospective study. Sao Paulo Med J. 2021;139(5):435-42. doi: 10.1590/1516-3180.2020.0470.R2.110321.
Oletić L, Šepec MP, Sabolić LL, Stipančić G. Turner Syndrome: for successful treatment it is necessary to diagnose it early. Minerva Endocrinol (Torino). 2021;46(1):99-106. doi: 10.23736/S2724-6507.20.03145-4.
Reimann GE, Bernad Perman MM, Ho PS, Parks RA, Comis LE. Psychosocial Characteristics of Women with a Delayed Diagnosis of Turner Syndrome. J Pediatr. 2018;199:206-11. doi: 10.1016/j.jpeds.2018.03.058.
Jung M de P, Amaral JL do, Fontes RG, Costa AT da, Wuillaume SM, Cardoso MHC de A. Diagnóstico da Síndrome de Turner: a experiência do Instituto Estadual de Diabetes e Endocrinologia - Rio de Janeiro, de 1970 a 2008. Rev Bras Saude Mater Infant [Internet]. 2010;10(1):117–24. Available from: https://doi.org/10.1590/S1519-38292010000100012
Massa GG, Vanderschueren-Lodeweyckx M. Age and height at diagnosis in Turner syndrome: influence of parental height. Pediatrics. 1991;88(6):1148-52.
Massa G, Verlinde F, De Schepper J, Thomas M, Bourguignon JP, Craen M, et al. Trends in age at diagnosis of Turner syndrome. Arch Dis Child. 2005;90(3):267-8. doi: 10.1136/adc.2004.049817.
Makishima T, King K, Brewer CC, Zalewski CK, Butman J, Bakalov VK, et al. Otolaryngologic markers for the early diagnosis of Turner syndrome. Int J Pediatr Otorhinolaryngol. 2009;73(11):1564-7. doi: 10.1016/j.ijporl.2009.08.005.
Carvalho AB, Guerra Júnior G, Baptista MT, de Faria AP, Marini SH, Guerra AT. Cardiovascular and renal anomalies in Turner syndrome. Rev Assoc Med Bras (1992). 2010;56(6):655-9. doi: 10.1590/s0104-42302010000600012.
Carpini S, Carvalho AB, Guerra-Júnior G, Baptista MT, Lemos-Marini SH, Maciel-Guerra AT. Spontaneous puberty in girls with early diagnosis of Turner syndrome. Arq Bras Endocrinol Metabol. 2012;56(9):653-7. doi: 10.1590/s0004-27302012000900009.
Gutin L, Collier S, Bakalov VK, Bondy C. Trends in GH use in a Turner syndrome natural history study. Pediatr Endocrinol Rev. 2012;9 Suppl 2(Suppl 2):725-7.
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(11):E2125-32. doi: 10.1210/jc.2012-1739.
Eckhauser A, South ST, Meyers L, Bleyl SB, Botto LD. Turner Syndrome in Girls Presenting with Coarctation of the Aorta. J Pediatr. 2015;167(5):1062-6. doi: 10.1016/j.jpeds.2015.08.002.
Hoxha P, Babameto-Laku A, Vyshka G, Gjoka K, Minxuri D, Myrtaj E, et al. Turner syndrome in Albania and the efficacy of its treatment with growth hormone. J Pediatr Endocrinol Metab. 2015;28(11-12):1227-34. doi: 10.1515/jpem-2014-0350.
Ríos Orbañanos I, Vela Desojo A, Martinez-Indart L, Grau Bolado G, Rodriguez Estevez A, Rica Echevarria I. Turner syndrome: From birth to adulthood. Endocrinol Nutr. 2015;62(10):499-506. English, Spanish. doi: 10.1016/j.endonu.2015.06.010.
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(3):264-6. doi: 10.1016/j.ijgo.2014.11.025.
Saikia UK, Sarma D, Yadav Y. Delayed Presentation of Turner Syndrome: Challenge to Optimal Management. J Hum Reprod Sci. 2017;10(4):297-301. doi: 10.4103/jhrs.JHRS_114_17.
Apperley L, Das U, Ramakrishnan R, Dharmaraj P, Blair J, Didi M, et al. Mode of clinical presentation and delayed diagnosis of Turner syndrome: a single Centre UK study. Int J Pediatr Endocrinol. 2018;2018:4. doi: 10.1186/s13633-018-0058-1.
Falhammar H, Claahsen-van der Grinten H, Reisch N, Slowikowska-Hilczer J, Nordenström A, Roehle R, et al. Health status in 1040 adults with disorders of sex development (DSD): a European multicenter study. Endocr Connect. 2018;7(3):466-78. doi: 10.1530/EC-18-0031.
Gawlik AM, Hankus M, Szeliga K, Antosz A, Gawlik T, Soltysik K, et al. Late-Onset Puberty Induction by Transdermal Estrogen in Turner Syndrome Girls-A Longitudinal Study. Front Endocrinol (Lausanne). 2018;9:23. doi: 10.3389/fendo.2018.00023.
Ouarezki Y, Cizmecioglu FM, Mansour C, Jones JH, Gault EJ, Mason A, et al. Measured parental height in Turner syndrome-a valuable but underused diagnostic tool. Eur J Pediatr. 2018;177(2):171-9. doi: 10.1007/s00431-017-3045-2.
Berglund A, Viuff MH, Skakkebæk A, Chang S, Stochholm K, Gravholt CH. Changes in the cohort composition of turner syndrome and severe non-diagnosis of Klinefelter, 47,XXX and 47,XYY syndrome: a nationwide cohort study. Orphanet J Rare Dis. 2019;14(1):16. doi: 10.1186/s13023-018-0976-2.
Kilinc S, Yildiz M, Guven A. Associated clinical abnormalities among patients with Turner syndrome. North Clin Istanb. 2020;7(3):226-30. doi: 10.14744/nci.2019.84758.
Swauger S, Backeljauw P, Hornung L, Shafer J, Casnellie L, Gutmark-Little I. Age at and indication for diagnosis of Turner syndrome in the pediatric population. Am J Med Genet A. 2021;185(11):3411-7. doi: 10.1002/ajmg.a.62459.
Gambineri A, Scarano E, Rucci P, Perri A, Tamburrino F, Altieri P, et al. New insights into the comorbid conditions of Turner syndrome: results from a long-term monocentric cohort study. J Endocrinol Invest. 2022;45(12):2247-56. doi: 10.1007/s40618-022-01853-z.
de Marqui AB, da Silva-Grecco RL, Balarin MA. Prevalência de sequências do Y e de gonadoblastoma em síndrome de Turner [Prevalence of Y-chromosome sequences and gonadoblastoma in Turner syndrome]. Rev Paul Pediatr. 2016;34(1):114-21. doi: 10.1016/j.rpped.2015.06.007.
Miguel Neto J, Marini SHVL, Faria APM, Guerra Júnior G, Guerra ATM. Fatores associados a atraso no diagnóstico da síndrome de Turner. Rev Paul Pediatr 2011;29(1):67-72.
Bispo AV, 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(4):4243-50. doi: 10.4238/2013.March.13.13.
Tuke MA, Ruth KS, Wood AR, Beaumont RN, Tyrrell J, Jones SE, et al. Mosaic Turner syndrome shows reduced penetrance in an adult population study. Genet Med. 2019;21(4):877-86. doi: 10.1038/s41436-018-0271-6.
Guzmán-Arias EC, Grajales-Restrepo DA, Zuluaga-Espinosa NA, Lopera-Cañaveral MV, Niño-Serna LF. Caracterización de una cohorte de pacientes pediátricas con Síndrome de Turner [Clinical characterization of girls with Turner syndrome]. Andes Pediatr. 2023;94(5):606-15. Spanish. doi: 10.32641/andespediatr.v94i5.4617.
Essaddam L, Zitouni O, Kraoua L, Trabelsi M, Sassi H, Kmiha S, et al. S. Turner syndrome: results of the first Tunisian study group on Turner syndrome (TuSGOT). J Pediatr Endocrinol Metab. 2023;36(6):577-83. doi: 10.1515/jpem-2022-0360.
de Araújo C, Galera BB, Galera MF, de Medeiros SF. Características clínicas e citogenéticas da síndrome de Turner na região Centro-Oeste do Brasil [Clinical and cytogenetic aspects of the Turner syndrome in the Brazilian Western region]. Rev Bras Ginecol Obstet. 2010;32(8):381-5. Portuguese. doi: 10.1590/s0100-72032010000800004.
McInnes RR, Willard HF, Nussbaum R. Thompson & Thompson Genética médica. Elsevier. 8ª ed., Rio de Janeiro: Elsevier, 2016.
Jorde LB, Carey JC, Bamshad MJ. Genética médica. 5ª ed., Rio de Janeiro, Editora Elsevier, 2017.
Ikomi C, Blatt J, Ghofrani S, Zhang R, Ross J, Law JR. Lymphedema in Turner syndrome: correlations with phenotype and karyotype. J Pediatr Endocrinol Metab. 2024;37(9):789-95. doi: 10.1515/jpem-2024-0174.
Brasil. Lei n.8.069, de 13 de julho de 1990. Dispõe sobre o Estatuto da Criança e do Adolescente e dá outras providências. 1990. Disponível em: https://www.planalto.gov.br/ccivil_03/Leis/L8069.htm
Aversa T, Li Pomi A, Pepe G, Corica D, Messina MF, Coco R, et al. Growth Hormone Treatment to Final Height in Turner Syndrome: Systematic Review. Clin Ther. 2024;46(2):146-53. doi: 10.1016/j.clinthera.2023.12.004.
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