DOI: https://doi.org/10.22141/2224-0721.15.3.2019.172108

Klinefelter syndrome in children and adolescents: combination of genetics and endocrinology

T.V. Sorokman, N.O. Popeliuk, O.V. Makarova

Abstract


The purpose was to analyze literature on the etiology and pathogenesis of Klinefelter syndrome (KS). The review of scientific literature regarding KS by the key words “Klinefelter syndrome”, Klinefelter-Reifenstein-Albright syndrome”, “pubertal underdevelopment of seminiferous tubules”, “syndrome 47, XXY” using PubMed as a search engine. Statistical data on KS are ambiguous. According to some authors, the frequency of births of children with KS defined as 1 case per 500–1000 live-birth boys further increases to 3–4 % among infertile men, and in patients with azoospermia, KS is diagnosed in 10–12 % of cases. Approximately 10 % of cases of KS is detected by prenatal diagnosis. Phenotypic variability may depend on the severity of genetic defects, androgen deficiency, androgen receptor sensitivity (CAG polymorphism) or accidental inactivation of the additional information of the X chromosome. Pediatricians should be aware of the phenotypic variability of the KS, in particular, to pay attention to mental and verbal disorders. It is also necessary to conduct a comprehensive molecular genetic study with medical genetic counseling for all children with ambiguous sexual organs. Timely prescribed therapy will able to minimize not only phenotypic manifestations of the syndrome, but also possibly postpone the rapid loss of spermatogenic cells, which will help these patients to realize their reproductive function.


Keywords


Klinefelter syndrome; clinical and genetic polymorphism; review

References


Herlihy AS, McLachlan R. Screening for Klinefelter syndrome. Curr Opin Endocrinol Diabetes Obes. 2015 Jun;22(3):224-9. doi: 10.1097/MED.0000000000000154.

Crawford D, Dearmun A. Klinefelter syndrome. Nurs Child Young People. 2017 Jul 10;29(6):19. doi: 10.7748/ncyp.29.6.19.s21.

Akcan N, Poyrazoğlu S, Bas F, Bundak R, Darendeliler F. Klinefelter Syndrome in Childhood: Variability in Clinical and Molecular Findings. J Clin Res Pediatr Endocrinol. 2018 Jun 1;10(2):100-107. doi: 10.4274/jcrpe.5121.

Leonard JM, Bremner WJ, Capell PT, Paulsen CA. Male hypogonadism: Klinefelter and Reifenstein syndromes. Birth Defects Orig Artic Ser. 1975;11(4):17-22.

Mandoki MW, Sumner GS, Hoffman RP, Riconda DL. A review of Klinefelter's syndrome in children and adolescents. J Am Acad Child Adolesc Psychiatry. 1991 Mar;30(2):167-72. doi: 10.1097/00004583-199103000-00001.

Klinefelter HF Jr, Reifenstein EC Jr, Albright F. Syndrome characterized by gynecomastia, aspermatogenesis without a-Leydigism and increased excretion of follicle-stimulating hormone. The Journal of Clinical Endocrinology. 1942;2(11):615-624. doi:10.1210/jcem-2-11-615.

Klinefelter HF. Klinefelter syndrome: historical background and development. South Med J. 1986 Sep;79(9):1089-93.

Jacobs PA, Strong JA. A case of human intersexuality having a possible XXY sex-determining mechanism. Nature. 1959 Jan 31;183(4657):302-3.

Fraser JH, Boyd E, Lennox B, Dennison WM. A case of XXXXY Klinefelter’s syndrome. Lancet. 1961 Nov 11;2(7211):1064-7.

Forti G, Corona G, Vignozzi L, Krausz C, Maggi M. Klinefelter’s syndrome: a clinical and therapeutical update. Sex Dev. 2010 Sep;4(4-5):249-58. doi: 10.1159/000316604.

Flannigan R, Schlegel PN. Genetic diagnostics of male infertility in clinical practice. Best Pract Res Clin Obstet Gynaecol. 2017 Oct;44:26-37. doi: 10.1016/j.bpobgyn.2017.05.002.

Anagnostopoulos AK, Kolialexi A, Mavrou A, et al. Proteomic analysis of amniotic fluid in pregnancies with Klinefelter syndrome foetuses. J Proteomics. 2010 Mar 10;73(5):943-50. doi: 10.1016/j.jprot.2009.12.009.

Bojesen A, Juul S, Gravholt CH. Prenatal and postnatal prevalence of Klinefelter syndrome: a national registry study. J Clin Endocrinol Metab. 2003 Feb;88(2):622-6. doi: 10.1210/jc.2002-021491.

Samango-Sprouse C. Expansion of the phenotypic profile of the young child with XXY. Pediatr Endocrinol Rev. 2010 Dec;8 Suppl 1:160-8.

St John M, Ponchard C, van Reyk O, et al. Speech and language in children with Klinefelter syndrome. J Commun Disord. 2019 Mar - Apr;78:84-96. doi: 10.1016/j.jcomdis.2019.02.003.

Boone KB, Swerdloff RS, Miller BL, et al. Neuropsychological profiles of adults with Klinefelter syndrome. J Int Neuropsychol Soc. 2001 May;7(4):446-56.

Calogero AE, Giagulli VA, Mongioì LM, et al. Klinefelter syndrome: cardiovascular abnormalities and metabolic disorders. J Endocrinol Invest. 2017 Jul;40(7):705-712. doi: 10.1007/s40618-017-0619-9.

Lee HS, Park CW, Lee JS, Seo JT. Hypogonadism Makes Dyslipidemia in Klinefelter's Syndrome. J Korean Med Sci. 2017 Nov;32(11):1848-1851. doi: 10.3346/jkms.2017.32.11.1848.

Brinton LA. Breast cancer risk among patients with Klinefelter syndrome. Acta Paediatr. 2011 Jun;100(6):814-8. doi: 10.1111/j.1651-2227.2010.02131.x. 

Wikström AM, Dunkel L. Klinefelter syndrome. Best Pract Res Clin Endocrinol Metab. 2011 Apr;25(2):239-50. doi: 10.1016/j.beem.2010.09.006. 

Crawford D, Dearmun A. Klinefelter syndrome. Nurs Child Young People. 2017 Jul 10;29(6):19. doi: 10.7748/ncyp.29.6.19.s21.

Balercia G, Bonomi M, Giagulli VA, et al. Thyroid function in Klinefelter syndrome: a multicentre study from KING group. J Endocrinol Invest. 2019 Mar 25. doi: 10.1007/s40618-019-01037-2.

Groth KA, Skakkebaek A, Host C, Gravholt CH, Bojesen A. Clinical review: Klinefelter syndrome a clinical update. J Clin Endocrinol Metab. 2013 Jan;98(1):20-30. doi: 10.1210/jc.2012-2382.

Mohd Nor NS, Jalaludin MY. A rare 47 XXY/46 XX mosaicism with clinical features of Klinefelter syndrome. Int J Pediatr Endocrinol. 2016;2016:11. doi: 10.1186/s13633-016-0029-3.

Garcia-Quevedo L, Blanco J, Sarrate Z, Català V, Bassas L, Vidal F. Hidden mosaicism in patients with Klinefelter’s syndrome: implications for genetic reproductive counseling. Hum Reprod. 2011 Dec;26(12):3486-93. doi: 10.1093/humrep/der351.

Kurková S, Zemanová Z, Hána V, et al. Molecular cytogenetic diagnosis of Klinefelter's syndrome in men more frequently detects sex chromosome mosaicism than classical cytogenetic methods. Cas Lek Cesk. 1999 Apr 19;138(8):235-8.

Tartaglia N, Ayari N, Howell S, D'Epagnier C, Zeitler P. 48,XXYY, 48,XXXY and 49, XXXXY syndromes: not just variants of Klinefelter syndrome. Acta Paediatr. 2011 Jun;100(6):851-60. doi: 10.1111/j.1651-2227.2011.02235.x.

Lakshmi C, Swarnalakshimi S. Acne in Klinefelter Syndrome-46XY/47XXY Mosaicism? Indian J Dermatol. 2015 Sep-Oct;60(5):494-6. doi: 10.4103/0019-5154.164373.

Velissariou V, Christopoulou S, Karadimas C, et al. Rare XXY/XX mosaicism in a phenotypic male with Klinefelter syndrome: case report. Eur J Med Genet. 2006 Jul-Aug;49(4):331-7. doi: 10.1016/j.ejmg.2005.09.001.

Visootsak J, Aylstock M, Graham JM Jr. Klinefelter syndrome and its variants: an update and review for the primary pediatrician. Clin Pediatr (Phila). 2001 Dec;40(12):639-51. doi: 10.1177/000992280104001201.

Giltay JC, Maiburg MC. Klinefelter syndrome: clinical and molecular aspects. Expert Rev Mol Diagn. 2010 Sep;10(6):765-76. doi: 10.1586/erm.10.63.

Quigley CA, De Bellis A, Marschke KB, el-Awady MK, Wilson EM, French FS. Androgen receptor defects: historical, clinical and molecular perspectives. Endocr Rev. 1995 Jun;16(3):271-321. doi: 10.1210/edrv-16-3-271.

Valente U, Vinanzi C, Dipresa S, et al. Is there any clinical relevant difference between non mosaic Klinefelter Syndrome patients with or without Androgen Receptor variations? Sci Rep. 2017 Jun 13;7(1):3358. doi: 10.1038/s41598-017-03371-y.

Tuttelmann F, Gromoll J. Novel genetic aspects of Klinefelter’s syndrome. Mol Hum Reprod. 2010 Jun;16(6):386-95. doi: 10.1093/molehr/gaq019.

Fan G, Tran J. X-chromosome inactivation in human and mouse pluripotent stem cells. Hum Genet. 2011 Aug;130(2):217-22. doi: 10.1007/s00439-011-1038-1.

Yang F, Babak T, Shendure J, Disteche CM. Global survey of escape from X-inactivation by RNA-sequencing in mouse. Genome Res. 2010 May;20(5):614-22. doi: 10.1101/gr.103200.109

Rocca VS, Pecile V, Cleva L, e al. The Klinefelter syndrome is associated with high recurrence of copy number variations on the X-chromosome with a potential role in the clinical phenotype. Andrology. 2016 Mar;4(2):328-34. doi: 10.1111/andr.12146.

Huang J, Zhang L, Deng H, Chang L, Liu Q, Liu P. Global transcriptome analysis of peripheral blood identifies the most significantly down-regulated genes associated with metabolism regulation in Klinefelter syndrome. Mol Reprod Dev. 2015 Jan;82(1):17-25. doi: 10.1002/mrd.22438.

Salemi M, Cannarella R, Condorelli RA, et al. Evidence for long noncoding RNA GAS5 up-regulationin patients with Klinefelter syndrome. BMC Med Genet. 2019 Jan 7;20(1):4. doi: 10.1186/s12881-018-0744-0.

Skakkebæk A, Nielsen MM, Trolle C, et al. DNA hypermethylation and differential gene expression associated with Klinefelter syndrome. Sci Rep. 2018 Sep 13;8(1):13740. doi: 10.1038/s41598-018-31780-0.

Yu YH, Siao FP, Hsu LC, Yen PH. TEX11 modulates germ cell proliferation by competing with estrogen receptor beta for the binding to HPIP. Mol Endocrinol. 2012 Apr;26(4):630-42. doi: 10.1210/me.2011-1263.

Groth KA, Skakkeaek A, Host C, Gravholt CH, Bojesen A. Clinical review: Klinefelter syndrome –a clinical update. J Clin Endocrinol Metab. 2013 Jan;98(1):20-30. doi: 10.1210/jc.2012-2382.

Blaschke RJ, Rappold G. The pseudoautosomal regions, SHOX and disease. Curr Opin Genet Dev. 2006 Jun;16(3):233-9. doi: 10.1016/j.gde.2006.04.004.

Berletch JB, Yang F, Xu J, Carrel L, Disteche CM. Genes that escape from X-inactivation. Hum Genet. 2011 Aug;130(2):237-45. doi: 10.1007/s00439-011-1011-z.

Yu YH, Siao FP, Hsu LC, Yen PH. TEX11 modulates germ cell proliferation by competing with estrogen receptor beta for the binding to HPIP. Mol Endocrinol. 2012 Apr;26(4):630-42. doi: 10.1210/me.2011-1263.






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