Klinefelter syndrome: a comprehensive review beyond the 47 XXY karyotype

Authors

  • Diana Katerine Guevara Márquez Universidad Antonio Nariño
  • Germán Augusto Méndez García Universidad Antonio Nariño

DOI:

https://doi.org/10.54104/saywa.v4n5.1588

Keywords:

chromosomal aberration, Karyotype 47XXY, systematic review., Klinefelter syndrome (KS)

Abstract

Klinefelter syndrome is a pathological condition caused by a chromosomal aberration in males, resulting in the most common alteration of sex chromosomes in humans, characterized by a karyotype of 47 XXY. Its prevalence ranges from 85 to 250 cases per 100,000 live births annually. The absence of clinical signs during early decades of life often leads to a delayed diagnosis, which is associated with metabolic, vascular, and hormonal alterations that negatively impact individuals with this condition.

Due to the high prevalence and underdiagnosis of Klinefelter syndrome, it is crucial to understand the genetic and epigenetic processes underlying the disease's development and recognize the accompanying clinical signs. A systematic review of literature was conducted in major medical research databases to achieve this objective. After applying inclusion criteria, 50 relevant articles were analyzed and consolidated to create an updated document. This comprehensive review serves as an important guide for understanding and approaching patients with Klinefelter syndrome, based on scientific evidence.

By enhancing awareness and knowledge about this complex medical condition, healthcare professionals can improve early diagnosis, intervention, and management strategies for individuals affected by Klinefelter syndrome.

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References

Akcan, N., Poyrazoğlu, Ş., Baş, F., Bundak, R., & Darendeliler, F. (2018). Klinefelter Syndrome in Childhood: Variability in Clinical and Molecular Findings. Journal of Clinical Research in Pediatric Endocrinology, 100-107. DOI: https://doi.org/10.4274/jcrpe.5121

Aliberti, L., Gagliardi, L., & Bigoni, S. (2022). Communicating the diagnosis of Klinefelter syndrome to children and adolescents: when, how, and who? J Community Genet, 313-321. DOI: https://doi.org/10.1007/s12687-022-00585-0

Alowaysi, M., Fiacco, E., Astro, V., & Adamo, A. (2020). Establishment of iPSC lines from a high- grade Klinefelter Syndrome patient (49-XXXXY) and two genetically matched healthy relatives (KAUSTi003-A, KAUSTi004-A, KAUSTi004-B, KAUSTi005-A, KAUSTi005-B, KAUSTi005-C). Stem Cell Res, 245-255. DOI: https://doi.org/10.1016/j.scr.2020.102008

Alowaysi, M., Fiacco, E., Astro, V., & Adamo, A. (2020). Establishment of an iPSC cohort from three unrelated 47-XXY Klinefelter Syndrome patients (KAUSTi007-A, KAUSTi007-B, KAUSTi009- A, KAUSTi009-B, KAUSTi010-A, KAUSTi010-B). Stem Cell Res, 152-158. DOI: https://doi.org/10.1016/j.scr.2020.102042

Bar, G., Lunenfeld, E., & Levitas, E. (2014). Klinefelter syndrome: genetic aspects, characteristics and reproduction--present and future. Israel Medicine Association, 342 - 366.

Bearelly, P., & Oates, R. (2019). Recent advances in managing and understanding Klinefelter syndrome. F1000 research, 112-123. DOI: https://doi.org/10.12688/f1000research.16747.1

Beumer, C., & Brehm, R. (2020). 41,XX Y * male mice: An animal model for Klinefelter syndrome.

Am J Med Genet C Semin Med Genet, 267-278.

Bonomi, M., Rochira, V., Pasquali, D., Balercia, G., Jannini, E., & Ferlin, A. (2017). Klinefelter syndrome (KS): genetics, clinical phenotype and hypogonadism. journal of endocrinology investigation, 123-134. DOI: https://doi.org/10.1007/s40618-016-0541-6

Cannarella, R., Salemi, M., Condorelli, R., Cimino, L., Giurato, G. M., Cordella, A., . . . Calogero, A. (2021). SOX13 gene downregulation in peripheral blood mononuclear cells of patients with Klinefelter syndrome. Asian Journal of Andrology, 157-162. DOI: https://doi.org/10.4103/aja.aja_37_20

Central hypogonadism in Klinefelter syndrome: report of two cases and review of the literature. (2021). J Endocrinol Invest., 459-470.

Chang, S., Skakkebæk, A., & Højbjerg, G. (2015). Klinefelter Syndrome and medical treatment: hypogonadism and beyond. Hormones (Athens), 531-48. DOI: https://doi.org/10.14310/horm.2002.1622

Cimino, L., Salemi, M., Cannarella, R., Condorelli, R., Giurato, G., Marchese, G., . . . Calogero, A. (2017). Decreased miRNA expression in Klinefelter syndrome. Scientific Reports. DOI: https://doi.org/10.1038/s41598-017-16892-3

Crawford, D., & Dearmun, A. (2017). Klinefelter syndrome. Nurs Child Young People, 14-19. DOI: https://doi.org/10.7748/ncyp.29.6.19.s21

Finocchi, F., Pelloni, M., Balercia, G., Pallotti, F., Radicioni, A., Lenzi, A., . . . Paoli, D. (2020). Seminal plasma miRNAs in Klinefelter syndrome and in obstructive and non-obstructive azoospermia. Molecular Biology Reports, 4373-4382. DOI: https://doi.org/10.1007/s11033-020-05552-x

Franik, S., Smeets, D., van de Zande, G., Gomes, I., D'Hauwers, K., Braat, D., . . . Ramos, L. (2018).

Klinefelter syndrome and fertility-Impact of X-chromosomal inheritance on spermatogenesis. Andrologia.

Frühmesser, A., & Kotzot, D. (2012). Chromosomal variants in klinefelter syndrome. Sex Dev, 109- 123. DOI: https://doi.org/10.1159/000327324

Gravholt, C., Jensen, G., Høst, C., & Bojesen, A. (2012). Body composition, metabolic syndrome and type 2 diabetes in Klinefelter syndrome. Acta Paediatr, 871-7. DOI: https://doi.org/10.1111/j.1651-2227.2011.02233.x

Gravholt, C., Chang, S., Wallentin, M., Fedder, J., Moore, P., & Skakkebæk, A. (2018). Klinefelter Syndrome: Integrating Genetics, Neuropsychology, and Endocrinology. Journal of endocrinology , 389-423. DOI: https://doi.org/10.1210/er.2017-00212

Gravholt, C., Tartaglia, N., & Disteche, C. (2020). Sex chromosome aneuploidies in 2020-The state of care and research in the world. Am J Med Genet C Semin Med Genet., 197-201. DOI: https://doi.org/10.1002/ajmg.c.31808

Groth KA, S. A. (2013). Clinical review: Klinefelter syndrome--a clinical update. journal of clinical endocrinology and metabolism, 20-30. DOI: https://doi.org/10.1210/jc.2012-2382

Indirli, R., Profka, E., Castellano, E., & Goggi, G. (2021). Central hypogonadism in Klinefelter syndrome: report of two cases and review of the literature. J Endocrinol Invest., 459-470. DOI: https://doi.org/10.1007/s40618-020-01324-3

Kanakis, G., & Nieschlag, E. (2018). Klinefelter syndrome: more than hypogonadism. Metabolism, 135-144. DOI: https://doi.org/10.1016/j.metabol.2017.09.017

Li, X., Huang, S., Yuan, Y., Lu, Y., Zhang, D., Wang, X., . . . Dai, P. (2019). Detecting novel mutations and combined Klinefelter syndrome in Usher syndrome cases. Acta Otorrinolaringologica, 479-486. DOI: https://doi.org/10.1080/00016489.2019.1603397

Liu C, L. H. (2021). Paternal USP26 mutations raise Klinefelter syndrome risk in the offspring of mice and humans. The EMBO Journal , 1423-1433. DOI: https://doi.org/10.15252/embj.2020106864

Mahyari E, G. J.-C. (2021). Comparative single-cell analysis of biopsies clarifies pathogenic mechanisms in Klinefelter syndrome. The American Journal of Human Genetics, 1924- 1945. DOI: https://doi.org/10.1016/j.ajhg.2021.09.001

Maiburg, M., Repping, S., & Giltay, J. (2012). The genetic origin of Klinefelter syndrome and its effect on spermatogenesis. Fertility and Sterility, 253-60. DOI: https://doi.org/10.1016/j.fertnstert.2012.06.019

Navarro-Cobos, M., Balaton, B., & Brown, C. (2020). Genes that escape from X-chromosome inactivation: Potential contributors to Klinefelter syndrome. American Journal of Medical Genetics, 226-238. DOI: https://doi.org/10.1002/ajmg.c.31800

Nieschlag, E., Werler, S., Wistuba, J., & Zitzmann, M. (2014). New approaches to the Klinefelter syndrome. Annales d'Endocrinologie, 88-97. DOI: https://doi.org/10.1016/j.ando.2014.03.007

Özkent, M., & Balasar, Ö. (2021). A rare variant Klinefelter syndrome seen 40 years later: 47,X,del(Xq24),Y. andrologia. DOI: https://doi.org/10.1111/and.14213

Panula, S., Kurek, M., Kumar, P., Albalushi, H., & Padrell, S. (2019). Human induced pluripotent stem cells from two azoospermic patients with Klinefelter syndrome show similar X chromosome inactivation behavior to female pluripotent stem cells. Hum Reprod., 2297- 2310. DOI: https://doi.org/10.1093/humrep/dez134

Peña, V., Kohn, T., & Herati, A. (2020). Genetic mutations contributing to non-obstructive azoospermia . Best Practice & Research Clinical Endocrinology & Metabolism. DOI: https://doi.org/10.1016/j.beem.2020.101479

Radellini, S., Guarnotta, V., Sciabica, V., Pizzolanti, G., & Giordano, C. (2022). Metabolic Profile in a Cohort of Young Sicilian Patients with Klinefelter's Syndrome: The Role of Irisin. Int J Endocrinol, 1134-1149. DOI: https://doi.org/10.1155/2022/3780741

Salemi, M., Cannarella, R., Cimino, L., Condorelli, R., Giurato, G., Marchese, G., . . . Calogero, A. (2021). GPR56 gene down-regulation in patients with Klinefelter Syndrome: a candidate for infertility? Minerva Endocrinology, 384-388. DOI: https://doi.org/10.23736/S0391-1977.20.03357-X

Samango-Sprouse, C., Keen, C., Sadeghin, T., & Gropman, A. (2017). The benefits and limitations of cell-free DNA screening for 47, XXY (Klinefelter syndrome). Prenatal Diagnosis, 497-501. DOI: https://doi.org/10.1002/pd.5044

Samplaski, M., Kirk, L., & Grober, E. (2014). Phenotypic differences in mosaic Klinefelter patients as compared with non-mosaic Klinefelter patients. Fertil Steril., 950-955. DOI: https://doi.org/10.1016/j.fertnstert.2013.12.051

Skakkebaek, A., Viuff, M., Nielsen, M., & Gravholt, C. (2020). Epigenetics and genomics in Klinefelter syndrome. American Journal of Medical Genetics, 216-225. DOI: https://doi.org/10.1002/ajmg.c.31802

Skakkebæk, A., Wallentin, M., & Gravholt, C. (2021). Klinefelter syndrome or testicular dysgenesis: Genetics, endocrinology, and neuropsychology. Handbook of Clinical Neurology, 445-462. DOI: https://doi.org/10.1016/B978-0-12-820683-6.00032-4

Spaziani, M., & Radicioni, F. (2020). Metabolic and cardiovascular risk factors in Klinefelter syndrome. Am J Med Genet C Semin Med Genet, 334-343. DOI: https://doi.org/10.1002/ajmg.c.31792

Stouffs, K., Gheldof, A., Tournaye, H., Vandermaelen, D., Bonduelle, M., Lissens, W., & Seneca, S. (2016). Sertoli Cell-Only Syndrome: Behind the Genetic Scenes. BioMed Research International. DOI: https://doi.org/10.1155/2016/6191307

Tao, Y., & Shuoning, S. (2021). Glucose metabolic disorder in Klinefelter syndrome: a retrospective analysis in a single Chinese hospital and literature review. BMC Endocr Disord, 239-44.

Tong, J., Zhao, X., Wan, A., & Zhang, T. (2021). PGT or ICSI? The impression of NGS-based PGT outcomes in nonmosaic Klinefelter syndrome. Asian Journal of Andrology, 621-626Tong J, Zhao XM, Wan AR, Zhang T. DOI: https://doi.org/10.4103/aja.aja_30_21

Vloeberghs, V., Verheyen, G., Santos-Ribeiro, S., Staessen, C., Verpoest, W., Gies, I., & Tournaye, H. (2018). Is genetic fatherhood within reach for all azoospermic Klinefelter men? PLOS ONE. DOI: https://doi.org/10.1371/journal.pone.0200300

Willems, M., Gies, I., & Van Saen, D. (2020). Germ cell loss in Klinefelter syndrome: When and why? American Journal of Medical Genetics, 356-370. DOI: https://doi.org/10.1002/ajmg.c.31787

Winge, S., Soraggi, S., Schierup, M., Rajpert-De Meyts, E., & Almstrup, K. (2020). Integration and reanalysis of transcriptomics and methylomics data derived from blood and testis tissue of

men with 47,XXY Klinefelter syndrome indicates the primary involvement of Sertoli cells in the testicular pathogenesis. The American Journal of Human Genetics, 239-255.

Wistuba, J., Beumer, C., Brehm, R., & Gromoll, J. (2020). 41,XX Y * male mice: An animal model for Klinefelter syndrome. American Journal of Medical Genetics, 267-278. DOI: https://doi.org/10.1002/ajmg.c.31796

Yang, X., Wang, J., Nai, Z., & Yang, Y. (2021). Klinefelter syndrome: Advances in research. National journal of andrology, 269-273.

Yu, Z., Yang, J., & Liu, J. (2017). Microdissection testicular sperm extraction for patients with non- mosaic Klinefelter's syndrome: An update. National journal of andrology, 842-847.

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2023-06-06
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How to Cite

Guevara Márquez, D. K., & Méndez García, G. A. (2023). Klinefelter syndrome: a comprehensive review beyond the 47 XXY karyotype. REVISTA SAYWA, 4(5), 27–46. https://doi.org/10.54104/saywa.v4n5.1588

Issue

Vol. 4 No. 5 (2022)

Section

Ciencia Aplicada

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Copyright (c) 2022 Diana Katerine Guevara Márquez, Germán Augusto Méndez García

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This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

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