Prenatal diagnosis of non-mosaic sex chromosome abnormalities: a 10-year experience from a tertiary referral center

Xiaoqing Wu; Danhua Guo; Ying Li; Xiaorui Xie; Linjuan Su; Meiying Cai; Lin Zheng; Na Lin; Bin Liang; Hailong Huang; Liangpu Xu

doi:10.1515/jpm-2022-0552

Article

Prenatal diagnosis of non-mosaic sex chromosome abnormalities: a 10-year experience from a tertiary referral center

Xiaoqing Wu , Danhua Guo , Ying Li , Xiaorui Xie , Linjuan Su , Meiying Cai , Lin Zheng , Na Lin , Bin Liang , Hailong Huang and Liangpu Xu

Published/Copyright: May 5, 2023

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From the journal Journal of Perinatal Medicine Volume 51 Issue 7

Abstract

Objectives

The aim of this study was to explore the frequency and profile of non-mosaic sex chromosome abnormalities detected in prenatal diagnosis over the past 10 years.

Methods

We retrospectively reviewed pregnancies diagnosed with non-mosaic sex chromosome abnormalities between January 2012 and December 2021, using karyotyping and/or single nucleotide polymorphism (SNP) array. Maternal age, indications for testing, and outcomes were recorded.

Results

Traditional karyotyping identified 269 (0.90 %) cases of non-mosaic sex chromosome abnormalities among 29,832 fetuses, including 249 cases of numerical abnormalities, 15 unbalanced structural abnormalities, and 5 balanced structural abnormalities. The overall detection rate of common sex chromosome aneuploidies (SCAs) was 0.81 %, with 47,XXY, 47,XXX, 47,XYY, and 45,X accounting for 0.32 , 0.19, 0.17, and 0.13 % respectively. All showed a fluctuating upward trend over the study period, except for 45,X. During the first five years (2012–2016), the major indication for testing was advanced maternal age (AMA), followed by abnormal ultrasound, abnormal noninvasive prenatal testing (NIPT), and abnormal maternal serum screening (MSS). In the second five years (2017–2021), the most frequent indication was abnormal NIPT, followed by AMA, abnormal ultrasound, and abnormal MSS. Among the 7,780 cases that underwent SNP array in parallel, an additional 29 clinically significant aberrations were detected. The most frequent aberration was a microdeletion in the Xp22.31 region, which was associated with X-linked ichthyosis.

Conclusions

Fetal sex chromosome abnormalities are important findings in prenatal diagnosis. The application of NIPT and SNP array technology has greatly improved the detection of SCAs and submicroscopic aberrations associated with sex chromosomes.

Keywords: maternal serum screening; non-mosaic chromosome anomalies; noninvasive prenatal testing (NIPT); sex chromosomal aneuploidies (SCAs); single nucleotide polymorphism array (SNP array); traditional karyotyping

Corresponding authors: Hailong Huang and Liangpu Xu, Medical Genetic Diagnosis and Therapy Center of Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian, P.R. China; and Fujian Provincial Key Laboratory for Prenatal Diagnosis and Birth Defect, Fuzhou, Fujian, P.R. China, E-mail: huanghailong@fjmu.edu.cn, xiliangpu@fjmu.edu.cn

Xiaoqing Wu and Danhua Guo contributed equally to this work.

Funding source: Joint Funds for the innovation of science and Technology, Fujian province

Award Identifier / Grant number: 2020Y9135

Funding source: The Natural Science Foundation of Fujian Province

Award Identifier / Grant number: 2021J01413

Research funding: The Natural Science Foundation of Fujian Province, China (Grant No. 2021J01413). Key Special Projects of Fujian Provincial Department of Science and Technology (grant No. 2021YZ034011). Joint Funds for the innovation of science and Technology, Fujian province (Grant No.2020Y9135).
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Informed consent: Informed consent was obtained from all individuals included in this study.
Ethical approval: The present study was approved by the Protection of Human Ethics Committee of Fujian Provincial Maternity and Children’s Hospital. Written informed consent was obtained from each pregnant woman.

References

1. Robinson, A, Bender, BG, Linden, MG. Prognosis of prenatally diagnosed children with sex chromosome aneuploidy. Am J Med Genet 1992;44:365–8. https://doi.org/10.1002/ajmg.1320440319.Search in Google Scholar PubMed

2. Ratcliffe, SG, Butler, GE, Jones, M. Edinburgh study of growth and development of children with sex chromosome abnormalities. IV. Birth Defects. Orig Artic Ser 1990;26:1–44.Search in Google Scholar

3. Gotz, MJ, Johnstone, EC, Ratcliffe, SG. Criminality and antisocial behaviour in unselected men with sex chromosome abnormalities. Psychol Med 1999;29:953–62. https://doi.org/10.1017/s0033291799008594.Search in Google Scholar PubMed

4. Bojesen, A, Gravholt, CH. Klinefelter syndrome in clinical practice. Nat Clin Pract Urol 2007;4:192–204. https://doi.org/10.1038/ncpuro0775.Search in Google Scholar PubMed

5. Chen, X, Wang, X, Dong, G, Fu, J, Jiang, Y. Clinical features of girls with short stature among inv (9), Turner (45, X) and control individuals. J Pediatr Endocrinol Metabol 2017;30:431–6. https://doi.org/10.1515/jpem-2016-0341.Search in Google Scholar PubMed

6. Pieters, JJ, Kooper, AJ, van Kessel, AG, Braat, DD, Smits, AP. Incidental prenatal diagnosis of sex chromosome aneuploidies: health, behavior, and fertility. ISRN Obstet Gynecol 2011;2011:807106. https://doi.org/10.5402/2011/807106.Search in Google Scholar PubMed PubMed Central

7. Zhang, X, Yang, J, Li, Y, Ma, X, Li, R. Sex chromosome abnormalities and psychiatric diseases. Oncotarget 2017;8:3969–79. https://doi.org/10.18632/oncotarget.13962.Search in Google Scholar PubMed PubMed Central

8. Liu, Y, Chen, X, Zhao, S, Way, N, Yoshikawa, H, Zhang, G, et al.. Interactions between MAOA gene polymorphism and maternal parenting in predicting externalizing and internalizing problems and social competence among Chinese children: testing the genetic vulnerability and differential susceptibility models. Infant Child Dev 2017:e2024.10.1002/icd.2024Search in Google Scholar

9. Ryan, J, Carriere, I, Ritchie, K, Ancelin, ML. Involvement of GPR50 polymorphisms in depression: independent replication in a prospective elderly cohort. Brain Behav 2015;5:e00313. https://doi.org/10.1002/brb3.313.Search in Google Scholar PubMed PubMed Central

10. Piton, A, Gauthier, J, Hamdan, FF, Lafrenière, R, Yang, Y, Henrion, E, et al.. Systematic resequencing of X-chromosome synaptic genes in autism spectrum disorder and schizophrenia. Mol Psychiatr 2011;16:867–80. https://doi.org/10.1038/mp.2010.54.Search in Google Scholar PubMed PubMed Central

11. Samango-Sprouse, C, Brooks, MR, Lasutchinkow, P, Sadeghin, T, Powell, S, Hamzik, MP, et al.. The effect of early hormonal treatment (EHT) on expressive and receptive language capabilities in boys with 47,XXY (Klinefelter syndrome) during infancy and early childhood. Genet Med 2021;23:1017–22. https://doi.org/10.1038/s41436-021-01098-w.Search in Google Scholar PubMed

12. Zitzmann, M, Rohayem, J. Gonadal dysfunction and beyond: clinical challenges in children, adolescents, and adults with 47,XXY Klinefelter syndrome. Am J Med Genet C Semin Med Genet 2020;184:302–12. https://doi.org/10.1002/ajmg.c.31786.Search in Google Scholar PubMed

13. Samango-Sprouse, C, Lasutschinkow, P, Powell, S, Sadeghin, T, Gropman, A. The incidence of anxiety symptoms in boys with 47,XXY (Klinefelter syndrome) and the possible impact of timing of diagnosis and hormonal replacement therapy. Am J Med Genet A 2019;179:423–8. https://doi.org/10.1002/ajmg.a.61038.Search in Google Scholar PubMed

14. Mezei, G, Papp, C, Tóth-Pál, E, Beke, A, Papp, Z. Factors influencing parental decision making in prenatal diagnosis of sex chromosome aneuploidy. Obstet Gynecol 2004;104:94–101. https://doi.org/10.1097/01.aog.0000128171.14081.eb.Search in Google Scholar PubMed

15. Li, H, Mao, Y, Jin, J. The correlation between maternal age and fetal sex chromosome aneuploidies: a 8-year single institution experience in China. Mol Cytogenet 2021;14:25. https://doi.org/10.1186/s13039-021-00545-2.Search in Google Scholar PubMed PubMed Central

16. Nagy, B, Nagy, RG, Lazar, L, Schonleber, J, Papp, C, Rigo, JJr. Detection of sex chromosome aneuploidies using quantitative fluorescent PCR in the Hungarian population. Clin Chim Acta 2015;445:2–6. https://doi.org/10.1016/j.cca.2015.03.009.Search in Google Scholar PubMed

17. Gruchy, N, Vialard, F, Decamp, M, Choiset, A, Rossi, A, Le Meur, N, et al.. Pregnancy outcomes in 188 French cases of prenatally diagnosed Klinefelter syndrome. Hum Reprod 2011;26:2570–5. https://doi.org/10.1093/humrep/der193.Search in Google Scholar PubMed

18. Zheng, Y, Wan, S, Dang, Y, Song, T, Chen, B, Zhang, J. Clinical experience regarding the accuracy of NIPT in the detection of sex chromosome abnormality. J Gene Med 2020;22:e3199. https://doi.org/10.1002/jgm.3199.Search in Google Scholar PubMed

19. Wang, Y, Li, S, Wang, W, Dong, Y, Zhang, M, Wang, X, et al.. Cell-free DNA screening for sex chromosome aneuploidies by non-invasive prenatal testing in maternal plasma. Mol Cytogenet 2020;13:10. https://doi.org/10.1186/s13039-020-0478-5.Search in Google Scholar PubMed PubMed Central

20. Petersen, AK, Cheung, SW, Smith, JL, Bi, W, Ward, PA, Peacock, S, et al.. Positive predictive value estimates for cell-free noninvasive prenatal screening from data of a large referral genetic diagnostic laboratory. Am J Obstet Gynecol 2017;217:691.e1–6. https://doi.org/10.1016/j.ajog.2017.10.005.Search in Google Scholar PubMed

21. Xu, L, Huang, H, Lin, N, Wang, Y, He, D, Zhang, M, et al.. Non-invasive cell-free fetal DNA testing for aneuploidy: multicenter study of 31 515 singleton pregnancies in southeastern China. Ultrasound Obstet Gynecol 2020;55:242–7. https://doi.org/10.1002/uog.20416.Search in Google Scholar PubMed

22. Wu, X, Li, Y, Xie, X, Su, L, Cai, M, Lin, N, et al.. Clinical review of noninvasive prenatal testing: experience from 551 pregnancies with noninvasive prenatal testing-positive results in a tertiary referral center. J Mol Diagn 2020;22:1469–75. https://doi.org/10.1016/j.jmoldx.2020.09.008.Search in Google Scholar PubMed

23. Vlatkovic, IB, Hafner, T, Miskovic, B, Vicic, A, Poljak, B, Stipoljev, F. Prenatal diagnosis of sex chromosome aneuploidies and disorders of sex development--a retrospective analysis of 11-year data. J Perinat Med 2014;42:529–34. https://doi.org/10.1515/jpm-2013-0279.Search in Google Scholar PubMed

24. Zhu, Y, Lu, S, Bian, X, Wang, H, Zhu, B, Wang, H, et al.. A multicenter study of fetal chromosomal abnormalities in Chinese women of advanced maternal age. Taiwan J Obstet Gynecol 2016;55:379–84. https://doi.org/10.1016/j.tjog.2016.01.002.Search in Google Scholar PubMed

25. Gruchy, N, Blondeel, E, Le Meur, N, Joly-Helas, G, Chambon, P, Till, M, et al.. Pregnancy outcomes in prenatally diagnosed 47, XXX and 47, XYY syndromes: a 30-year French, retrospective, multicentre study. Prenat Diagn 2016;36:523–9. https://doi.org/10.1002/pd.4817.Search in Google Scholar PubMed

26. Gruchy, N, Vialard, F, Blondeel, E, Le Meur, N, Joly-Helas, G, Chambon, P, et al.. Pregnancy outcomes of prenatally diagnosed Turner syndrome: a French multicenter retrospective study including a series of 975 cases. Prenat Diagn 2014;34:1133–8. https://doi.org/10.1002/pd.4439.Search in Google Scholar PubMed

27. Katoh, K, Aiba, K, Fukushi, D, Yoshimura, J, Suzuki, Y, Mitsui, J, et al.. Clinical and molecular genetic characterization of two female patients harboring the Xq27.3q28 deletion with different ratios of X chromosome inactivation. Hum Mutat 2020;41:1447–60. https://doi.org/10.1002/humu.24058.Search in Google Scholar PubMed

28. Lachlan, KL, Youings, S, Costa, T, Jacobs, PA, Thomas, NS. A clinical and molecular study of 26 females with Xp deletions with special emphasis on inherited deletions. Hum Genet 2006;118:640–51. https://doi.org/10.1007/s00439-005-0081-1.Search in Google Scholar PubMed

29. Sukenik-Halevy, R, Reches, A, Bar-Shira, A, Simchoni, S, Goldstein, M, Orr-Ortreger, A, et al.. Microscopic chromosome Xp distal deletions--a challenging issue in prenatal genetic counseling. Prenat Diagn 2014;34:592–7. https://doi.org/10.1002/pd.4354.Search in Google Scholar PubMed

30. Takeichi, T, Akiyama, M. Inherited ichthyosis: non-syndromic forms. J Dermatol 2016;43:242–51. https://doi.org/10.1111/1346-8138.13243.Search in Google Scholar PubMed

Received: 2022-11-13

Accepted: 2023-03-27

Published Online: 2023-05-05

Published in Print: 2023-09-26

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Articles in the same Issue

https://doi.org/10.1515/jpm-2022-0552

Keywords for this article

maternal serum screening; non-mosaic chromosome anomalies; noninvasive prenatal testing (NIPT); sex chromosomal aneuploidies (SCAs); single nucleotide polymorphism array (SNP array); traditional karyotyping