References
- Klinefelter HFR, Reifenstein EC, Albright F. Syndrome Characterized by Gynecomastia, Aspermatogenesis without A-Leydigism, and Increased Excretion of Follicle-Stimulating Hormone. The Journal of Clinical Endocrinology & Metabolism 1942;2:615-27. https://doi.org/10.1210/jcem-2-11-615
- Jacobs PA, Strong JA. A case of human intersexuality having a possible XXY sex-determining mechanism. Nature 1959;183:302-3. https://doi.org/10.1038/183302a0
- Bojesen A, Juul S, Gravholt CH. Prenatal and postnatal prevalence of Klinefelter syndrome: a national registry study. J Clin Endocrinol Metab 2003;88:622-6. https://doi.org/10.1210/jc.2002-021491
- Gravholt CH, Chang S, Wallentin M, Fedder J, Moore P, Skakkebaek A. Klinefelter Syndrome: Integrating Genetics, Neuropsychology, and Endocrinology. Endocr Rev 2018;39:389-423. https://doi.org/10.1210/er.2017-00212
- Herlihy AS, McLachlan RI. Screening for Klinefelter syndrome. Curr Opin Endocrinol Diabetes Obes 2015;22:224-9. https://doi.org/10.1097/MED.0000000000000154
- Herlihy AS, Gillam L, Halliday JL, McLachlan RI. Postnatal screening for Klinefelter syndrome: is there a rationale? Acta Paediatr 2011;100:923-33. https://doi.org/10.1111/j.1651-2227.2011.02151.x
- Abramsky L, Chapple J. 47,XXY (Klinefelter syndrome) and 47,XYY: estimated rates of and indication for postnatal diagnosis with implications for prenatal counselling. Prenat Diagn 1997;17:363-8. https://doi.org/10.1002/(SICI)1097-0223(199704)17:4<363::AID-PD79>3.0.CO;2-O
- Coffee B, Keith K, Albizua I, Malone T, Mowrey J, Sherman SL, et al. Incidence of fragile X syndrome by newborn screening for methylated FMR1 DNA. Am J Hum Genet 2009;85:503-14. https://doi.org/10.1016/j.ajhg.2009.09.007
- Velissariou V, Christopoulou S, Karadimas C, Pihos I, Kanaka-Gantenbein C, Kapranos N, et al. Rare XXY/XX mosaicism in a phenotypic male with Klinefelter syndrome: case report. Eur J Med Genet 2006;49:331-7. https://doi.org/10.1016/j.ejmg.2005.09.001
- Tangshewinsirikul C, Dulyaphat W, Tim-Aroon T, Parinayok R, Chareonsirisuthigul T, Korkiatsakul V, et al. Klinefelter Syndrome Mosaicism 46,XX/47,XXY: A New Case and Literature Review. J Pediatr Genet 2020;9:221-6. https://doi.org/10.1055/s-0040-1713002
- Bergmann M, Schleicher G, Bocker R, Nieschlag E. True hermaphroditism with bilateral ovotestis: a case report. Int J Androl 1989;12:139-47. https://doi.org/10.1111/j.1365-2605.1989.tb01297.x
- Hamlett JD, Timson J, Harris R. XX-XXY mosaicism in a phenotypically normal female. Hum Hered 1970;20:260-4. https://doi.org/10.1159/000152319
- Kaufman RL, Rimoin DL, Woolf RB, Warren RJ, Sly WS. Sex chromosome mosaicism (XO-XX-XXY-XY) in a phenotypic female. JAMA 1971;215:1941-4. https://doi.org/10.1001/jama.1971.03180250033007
- Kelly TE, Franko JB, Rogol A, Golden WL. Discordant phenotypes and 45,X/46,X,idic(Y). J Med Genet 1998;35:862-4. https://doi.org/10.1136/jmg.35.10.862
- Reddy KS, Sulcova V. Pathogenetics of 45,X/46,XY gonadal mosaicism. Cytogenet Cell Genet 1998;82:52-7. https://doi.org/10.1159/000015064
- Quilter CR, Nathwani N, Conway GS, Stanhope R, Ralph D, Bahadur G, et al. A comparative study between infertile males and patients with Turner syndrome to determine the influence of sex chromosome mosaicism and the breakpoints of structurally abnormal Y chromosomes on phenotypic sex. J Med Genet 2002;39:e80. https://doi.org/10.1136/jmg.39.12.e80
- Bergman S, Nowakowski H, Reitalu J. Cytological and clinical observations in XXY-XX-XY-XO mosaicism. Hereditas 1969;61:276-8. https://doi.org/10.1111/j.1601-5223.1969.tb01841.x
- Zamora L, Espinet B, Salido M, Sole F, Ligorria C, Florensa L. Report of 46,XX/46,XY/47,XXY/48,XXYY mosaicism in an adult phenotypic male. Am J Med Genet 2002;111:215-7. https://doi.org/10.1002/ajmg.10561
- Visootsak J, Rosner B, Dykens E, Tartaglia N, Graham JM, Jr. Behavioral phenotype of sex chromosome aneuploidies: 48,XXYY, 48,XXXY, and 49,XXXXY. Am J Med Genet A 2007;143A:1198-203. https://doi.org/10.1002/ajmg.a.31746
- Tartaglia N, Davis S, Hench A, Nimishakavi S, Beauregard R, Reynolds A, et al. A new look at XXYY syndrome: medical and psychological features. Am J Med Genet A 2008;146A:1509-22. https://doi.org/10.1002/ajmg.a.32366
- 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;100:851-60. https://doi.org/10.1111/j.1651-2227.2011.02235.x
- Youssoufian H, Pyeritz RE. Mechanisms and consequences of somatic mosaicism in humans. Nat Rev Genet 2002;3:748-58. https://doi.org/10.1038/nrg906
- Skakkebaek A, Viuff M, Nielsen MM, Gravholt CH. Epigenetics and genomics in Klinefelter syndrome. Am J Med Genet C Semin Med Genet 2020;184:216-25. https://doi.org/10.1002/ajmg.c.31802
- Lanfranco F, Kamischke A, Zitzmann M, Nieschlag E. Klinefelter's syndrome. Lancet 2004;364:273-83. https://doi.org/10.1016/S0140-6736(04)16678-6
- Paduch DA, Fine RG, Bolyakov A, Kiper J. New concepts in Klinefelter syndrome. Curr Opin Urol 2008;18:621-7. https://doi.org/10.1097/MOU.0b013e32831367c7
- Garcia-Quevedo L, Blanco J, Sarrate Z, Catala V, Bassas L, Vidal F. Hidden mosaicism in patients with Klinefelter's syndrome: implications for genetic reproductive counselling. Hum Reprod 2011;26:3486-93. https://doi.org/10.1093/humrep/der351
- Jacobs P, Hassold T, Harvey J, May K. The origin of sex chromosome aneuploidy. Prog Clin Biol Res 1989;311:135-51.
- Tuttelmann F, Gromoll J. Novel genetic aspects of Klinefelter's syndrome. Mol Hum Reprod 2010;16:386-95. https://doi.org/10.1093/molehr/gaq019
- Ross JL, Roeltgen DP, Stefanatos G, Benecke R, Zeger MP, Kushner H, et al. Cognitive and motor development during childhood in boys with Klinefelter syndrome. Am J Med Genet A 2008;146A:708-19. https://doi.org/10.1002/ajmg.a.32232
- Zeger MP, Zinn AR, Lahlou N, Ramos P, Kowal K, SamangoSprouse C, et al. Effect of ascertainment and genetic features on the phenotype of Klinefelter syndrome. J Pediatr 2008;152:716-22. https://doi.org/10.1016/j.jpeds.2007.10.019
- Bojesen A, Gravholt CH. Morbidity and mortality in Klinefelter syndrome (47,XXY). Acta Paediatr 2011;100:807-13. https://doi.org/10.1111/j.1651-2227.2011.02274.x
- Skakkebaek A, Bojesen A, Kristensen MK, Cohen A, Hougaard DM, Hertz JM, et al. Neuropsychology and brain morphology in Klinefelter syndrome - the impact of genetics. Andrology 2014;2:632-40. https://doi.org/10.1111/j.2047-2927.2014.00229.x
- Chang S, Skakkebaek A, Gravholt CH. Klinefelter Syndrome and medical treatment: hypogonadism and beyond. Hormones (Athens) 2015;14:531-48.
- Valente U, Vinanzi C, Dipresa S, Selice R, Menegazzo M, Iafrate M, et al. Is there any clinical relevant difference between non mosaic Klinefelter Syndrome patients with or without Androgen Receptor variations? Sci Rep 2017;7:3358. https://doi.org/10.1038/s41598-017-03371-y
- Corbitt H, Morris SA, Gravholt CH, Mortensen KH, Tippner-Hedges R, Silberbach M, et al. TIMP3 and TIMP1 are risk genes for bicuspid aortic valve and aortopathy in Turner syndrome. PLoS Genet 2018;14:e1007692. https://doi.org/10.1371/journal.pgen.1007692
- Rocca MS, Pecile V, Cleva L, Speltra E, Selice R, Di Mambro A, et 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;4:328-34. https://doi.org/10.1111/andr.12146
- Skakkebaek A, Nielsen MM, Trolle C, Vang S, Hornshoj H, Hedegaard J, et al. DNA hypermethylation and differential gene expression associated with Klinefelter syndrome. Sci Rep 2018;8:13740. https://doi.org/10.1038/s41598-018-31780-0
- Belling K, Russo F, Jensen AB, Dalgaard MD, Westergaard D, Rajpert-De Meyts E, et al. Klinefelter syndrome comorbidities linked to increased X chromosome gene dosage and altered protein interactome activity. Hum Mol Genet 2017;26:1219-29. https://doi.org/10.1093/hmg/ddx014
- Passerini V, Ozeri-Galai E, de Pagter MS, Donnelly N, Schmalbrock S, Kloosterman WP, et al. The presence of extra chromosomes leads to genomic instability. Nat Commun 2016;7:10754. https://doi.org/10.1038/ncomms10754
- Zhang X, Hong D, Ma S, Ward T, Ho M, Pattni R, et al. Integrated functional genomic analyses of Klinefelter and Turner syndromes reveal global network effects of altered X chromosome dosage. Proc Natl Acad Sci U S A 2020;117:4864-73. https://doi.org/10.1073/pnas.1910003117
- Ross JL, Samango-Sprouse C, Lahlou N, Kowal K, Elder FF, Zinn A. Early androgen deficiency in infants and young boys with 47,XXY Klinefelter syndrome. Horm Res 2005;64:39-45.
- Bojesen A, Kristensen K, Birkebaek NH, Fedder J, Mosekilde L, Bennett P, et al. The metabolic syndrome is frequent in Klinefelter's syndrome and is associated with abdominal obesity and hypogonadism. Diabetes Care 2006;29:1591-8. https://doi.org/10.2337/dc06-0145
- Autio-Harmainen H, Rapola J, Aula P. Fetal gonadal histology in XXXXY, XYY and XXX syndromes. Clin Genet 1980;18:1-5. https://doi.org/10.1111/j.1399-0004.1980.tb01356.x
- Coerdt W, Rehder H, Gausmann I, Johannisson R, Gropp A. Quantitative histology of human fetal testes in chromosomal disease. Pediatr Pathol 1985;3:245-59. https://doi.org/10.3109/15513818509078785
- Murken JD, Stengel-Rutkowski S, Walther JU, Westenfelder SR, Remberger KH, Zimmer F. Letter: Klinefelter's syndrome in a fetus. Lancet 1974;2:171.
- Ratcliffe SG, Field MA. Emotional disorder in XYY children: four case reports. J Child Psychol Psychiatry 1982;23:401-6. https://doi.org/10.1111/j.1469-7610.1982.tb00086.x
- Boada R, Janusz J, Hutaff-Lee C, Tartaglia N. The cognitive phenotype in Klinefelter syndrome: a review of the literature including genetic and hormonal factors. Dev Disabil Res Rev 2009;15:284-94. https://doi.org/10.1002/ddrr.83
- Geschwind DH, Boone KB, Miller BL, Swerdloff RS. Neurobehavioral phenotype of Klinefelter syndrome. Ment Retard Dev Disabil Res Rev 2000;6:107-16. https://doi.org/10.1002/1098-2779(2000)6:2<107::AID-MRDD4>3.0.CO;2-2
- Host C, Skakkebaek A, Groth KA, Bojesen A. The role of hypogonadism in Klinefelter syndrome. Asian J Androl 2014;16:185-91. https://doi.org/10.4103/1008-682X.122201
- Kanakis GA, Nieschlag E. Klinefelter syndrome: more than hypogonadism. Metabolism 2018;86:135-44. https://doi.org/10.1016/j.metabol.2017.09.017
- Shiraishi K, Matsuyama H. Klinefelter syndrome: From pediatrics to geriatrics. Reprod Med Biol 2019;18:140-50. https://doi.org/10.1002/rmb2.12261
- Corona G, Pizzocaro A, Lanfranco F, Garolla A, Pelliccione F, Vignozzi L, et al. Sperm recovery and ICSI outcomes in Klinefelter syndrome: a systematic review and meta-analysis. Hum Reprod Update 2017;23:265-75. https://doi.org/10.1093/humupd/dmx008
- Price WH, Clayton JF, Wilson J, Collyer S, De Mey R. Causes of death in X chromatin positive males (Klinefelter's syndrome). J Epidemiol Community Health 1985;39:330-6. https://doi.org/10.1136/jech.39.4.330
- Isidori AM, Balercia G, Calogero AE, Corona G, Ferlin A, Francavilla S, et al. Outcomes of androgen replacement therapy in adult male hypogonadism: recommendations from the Italian society of endocrinology. J Endocrinol Invest 2015;38:103-12. https://doi.org/10.1007/s40618-014-0155-9
- Pasquali D, Arcopinto M, Renzullo A, Rotondi M, Accardo G, Salzano A, et al. Cardiovascular abnormalities in Klinefelter syndrome. Int J Cardiol 2013;168:754-9. https://doi.org/10.1016/j.ijcard.2012.09.215
- Bekaert M, Van Nieuwenhove Y, Calders P, Cuvelier CA, Batens AH, Kaufman JM, et al. Determinants of testosterone levels in human male obesity. Endocrine 2015;50:202-11. https://doi.org/10.1007/s12020-015-0563-4
- Zoller B, Ji J, Sundquist J, Sundquist K. High Risk of Venous Thromboembolism in Klinefelter Syndrome. J Am Heart Assoc 2016;5.
- Yabuno Y, Tosa M, Iwakiri I, Nomoto S, Kaneko M, Kuwahara K, et al. Refractory leg ulcers associated with Klinefelter syndrome. J Nippon Med Sch 2015;82:64-7. https://doi.org/10.1272/jnms.82.64
- Seminog OO, Seminog AB, Yeates D, Goldacre MJ. Associations between Klinefelter's syndrome and autoimmune diseases: English national record linkage studies. Autoimmunity 2015;48:125-8. https://doi.org/10.3109/08916934.2014.968918
- Ferlin A, Schipilliti M, Di Mambro A, Vinanzi C, Foresta C. Osteoporosis in Klinefelter's syndrome. Mol Hum Reprod 2010;16:402-10. https://doi.org/10.1093/molehr/gaq026
- Behre HM, Kliesch S, Leifke E, Link TM, Nieschlag E. Long-term effect of testosterone therapy on bone mineral density in hypogonadal men. J Clin Endocrinol Metab 1997;82:2386-90. https://doi.org/10.1210/jcem.82.8.4163
- Sawalha AH, Harley JB, Scofield RH. Autoimmunity and Klinefelter's syndrome: when men have two X chromosomes. J Autoimmun 2009;33:31-4. https://doi.org/10.1016/j.jaut.2009.03.006
- Radicioni AF, Ferlin A, Balercia G, Pasquali D, Vignozzi L, Maggi M, et al. Consensus statement on diagnosis and clinical management of Klinefelter syndrome. J Endocrinol Invest 2010;33:839-50. https://doi.org/10.1007/BF03350351
- Swerdlow AJ, Schoemaker MJ, Higgins CD, Wright AF, Jacobs PA, Group UKCC. Cancer incidence and mortality in men with Klinefelter syndrome: a cohort study. J Natl Cancer Inst 2005;97:1204-10. https://doi.org/10.1093/jnci/dji240
- Sasco AJ, Lowenfels AB, Pasker-de Jong P. Review article: epidemiology of male breast cancer. A meta-analysis of published case-control studies and discussion of selected aetiological factors. Int J Cancer 1993;53:538-49. https://doi.org/10.1002/ijc.2910530403
- Gomez-Raposo C, Zambrana Tevar F, Sereno Moyano M, Lopez Gomez M, Casado E. Male breast cancer. Cancer Treat Rev 2010;36:451-7. https://doi.org/10.1016/j.ctrv.2010.02.002
- Brinton LA. Breast cancer risk among patients with Klinefelter syndrome. Acta Paediatr 2011;100:814-8. https://doi.org/10.1111/j.1651-2227.2010.02131.x
- Nichols CR, Heerema NA, Palmer C, Loehrer PJ, Sr., Williams SD, Einhorn LH. Klinefelter's syndrome associated with mediastinal germ cell neoplasms. J Clin Oncol 1987;5:1290-4. https://doi.org/10.1200/JCO.1987.5.8.1290
- Ji J, Zoller B, Sundquist J, Sundquist K. Risk of solid tumors and hematological malignancy in persons with Turner and Klinefelter syndromes: A national cohort study. Int J Cancer 2016;139:754-8. https://doi.org/10.1002/ijc.30126
- De Sanctis V, Fiscina B, Soliman A, Giovannini M, Yassin M. Klinefelter syndrome and cancer: from childhood to adulthood. Pediatr Endocrinol Rev 2013;11:44-50.
- Geraedts JP, Mol A, Briet E, Hartgrink-Groeneveld CA, den Ottolander GJ. Klinefelter syndrome: predisposition to acute nonlymphocytic leukaemia?. Lancet 1980;1:774.
- Horsman DE, Pantzar JT, Dill FJ, Kalousek DK. Klinefelter's syndrome and acute leukemia. Cancer Genet Cytogenet 1987;26:375-6. https://doi.org/10.1016/0165-4608(87)90073-2