Klinefelter's syndrome: A clinical and therapeutical update

Sexual Development

Volumn 4, Issue 4-5, 2010, Pages 249-258

  Forti, G ^a   Corona, G ^b   Vignozzi, L ^a   Krausz, C ^a   Maggi, M ^a  

^a UNIVERSITY OF FLORENCE   (Italy)

^b BELLARIA HOSPITAL   (Italy)

Author keywords

Azoospermia; Cryptozoospermia; Gynecomastia; Hypogonadism; Infertility; Testicular biopsy; Testicular sperm extraction; Testosterone; XX male; XXY karyotype

Indexed keywords

COGNITION; FERTILITY; HUMAN; KLINEFELTER SYNDROME; MALE; PATHOLOGY; PATHOPHYSIOLOGY; PHENOTYPE; PHYSIOLOGY; REVIEW;

COGNITION; FERTILITY; HUMANS; KLINEFELTER SYNDROME; MALE; PHENOTYPE;

EID: 84882321752     PISSN: 16615425     EISSN: 16615433     Source Type: Journal    
DOI: 10.1159/000316604     Document Type: Article

References (65)

1. Aksglaede L, Wikström AM, Rajpert-De Meyts E, Dunkel L, Skakkebaek NE, et al: Natural history of seminiferous tubule degeneration in Klinefelter syndrome. Hum Reprod Update 12: 39-48 (2006).
2. Aksglaede L, Petersen JH, Main KM, Skakkebaek NE, Juul A: High normal testosterone levels in infants with non-mosaic Klinefelter's syndrome. Eur J Endocrinol 157: 345-350 (2007).
3. Aksglaede L, Molgaard C, Skakkebaek NE, Juul A: Normal bone mineral content but unfavourable muscle/fat ratio in Klinefelter syndrome. Arch Dis Child 93: 30-34 (2008a).
4. Aksglaede L, Skakkebaek N, Juul A: Abnormal sex chromosome constitution and longitudinal growth: serum levels of insulin-like growth factor (IGF)-I, IGF binding protein-3, luteinizing hormone, and testosterone in 109 males with 47,XXY, 47XYY, or sex-determining region of the Y chromosome ( SRY )-positive 46,XX karyotypes. J Clin Endocrinol Metab 93: 169-176 (2008b).
5. Bender B, Puck M, Salbenblatt J: Cognitive development of children with sex chromosome abnormalities, in Smith S (ed): Genetics and Learning Disabilities, pp 175-201 (College Hill Press, San Diego 1986).
6. Bender BG, Linden MG, Robinson A: Verbal and spatial processing efficiency in 32 children with sex chromosome abnormalities. Pediatr Res 25: 577-579 (1989).
7. Bender BG, Linden MG, Robinson A: Neuropsychological impairment in 42 adolescents with sex chromosome abnormalities. Am J Med Genet 48: 169-173 (1993).
8. Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, et al: Testosterone therapy in adult men with androgen deficiency syndromes: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 91: 1995-2010 (2006).
9. Bjørn AM, Bojesen A, Gravholt CH, Laurberg P: Hypothyroidism secondary to hypothalamic-pituitary dysfunction may be part of the phenotype in Klinefelter syndrome: a casecontrol study. J Clin Endocrinol Metab 94: 2478-2481 (2009).
10. 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 15: 284-294 (2009).
11. Bojesen A, Juul S, Gravholt CH: Prenatal and postnatal prevalence of Klinefelter syndrome: a national registry study. J Clin Endocrinol Metab 88: 622-626 (2003).
12. Bojesen A, Juul S, Birkebaek N, Gravholt CH: Increased mortality in Klinefelter syndrome. J Clin Endocrinol Metab 89: 3830-3834 (2004).
13. Bojesen A, Juul S, Birkebaek NH, Gravholt CH: Morbidity in Klinefelter syndrome: a Danish register study based on hospital discharge diagnoses. J Clin Endocrinol Metab 91: 1254-1260 (2006a).
14. Bojesen A, Kristensen K, Birkebaek NH, Fedder J, Mosekilde L, et al: The metabolic syndrome is frequent in Klinefelter's syndrome and is associated with abdominal obesity and hypogonadism. Diabetes Care 29: 1591-1598 (2006b).
15. Boucekkine C, Toublanc JE, Abbas N, Chaabouni S, Ouahid S, et al: Clinical and anatomical spectrum in XX sex reversed patients. Relationship to the presence of Y specific DNAsequences. Clin Endocrinol 40: 733-742 (1994).
16. Bruining H, Swaab H, Kas M, van Engeland H: Psychiatric characteristics in a self-selected sample of boys with Klinefelter syndrome. Pediatrics 123:e865-e870 (2009).
17. Corona G, Mannucci E, Petrone L, Balercia G, Fisher AD, et al: ANDROTEST: a structured interview for the screening of hypogonadism in patients with sexual dysfunction. J Sex Med 3: 706-715 (2006).
18. Corona G, Petrone L, Paggi F, Lotti F, Boddi V, et al: Sexual dysfunction in subjects with Klinefelter's syndrome. Int J Androl 2009, Epub ahead of print.
19. Crown S, Crisp AH: A short clinical diagnostic self-rating scale for psychoneurotic patients. The Middlesex Hospital Questionnaire (M.H.Q.). Br J Psychiatry 112: 917-923 (1966).
20. DeLisi LE, Maurizio AM, Svetina C, Ardekani B, Szulc K, et al: Klinefelter's syndrome (XXY) as a genetic model for psychotic disorders. Am J Med Genet B Neuropsychiatr Genet 135B:15-23 (2005).
21. Eskenazi B, Wyrobek AJ, Kidd SA, Lowe X, Moore D 2nd, et al: Sperm aneuploidy in fathers of children with paternally and maternally inherited Klinefelter syndrome. Hum Reprod 17: 576-583 (2002).
22. Ferlin A, Garolla A, Foresta C: Chromosome abnormalities in sperm of individuals with constitutional sex chromosomal abnormalities. Cytogenet Genome Res 111: 310-316 (2005).
23. Ferlin A, Garolla A, Rigon F, Rasi Caldogno L, Lenzi A, et al: Changes in serum insulin-like factor 3 during normal male puberty. J Clin Endocrinol Metab 91: 3426-3431 (2006).
24. Foresta C, Ruzza G, Mioni R, Meneghello A, Baccichetti C: Testosterone and bone loss in Klinefelter syndrome. Horm Metab Res 15: 56-57 (1983).
25. Forti G, Giusti G, Borghi A, Pazzagli M, Fiorelli G, et al: Klinefelter's syndrome: a study of its hormonal plasma pattern. J Endocrinol Invest 1: 149-154 (1978).
26. Fullerton G, Hamilton M, Maheshwari A: Should non-mosaic Klinefelter syndrome men be labelled as infertile in 2009? Hum Reprod 25: 588-597 (2010).
27. Gabrilove JL, Freiberg EK, Thornton JC, Nicolis GL: Effect of age on testicular function in patients with Klinefelter's syndrome. Clin Endocrinol 11: 343-347 (1979).
28. Giedd JN, Clasen LS, Wallace GL, Lenroot RK, Lerch JP, et al: XXY (Klinefelter syndrome): a pediatric quantitative brain magnetic resonance imaging case-control study. Pediatrics 119:e232-e240 (2007).
29. Itti E, Gaw Gonzalo IT, Boone KB, Geschwind DH, Berman N, et al: Functional neuroimaging provides evidence of anomalous cerebral laterality in adults with Klinefelter's syndrome. Ann Neurol 54: 669-673 (2003).
30. Itti E, Gaw Gonzalo IT, Pawlikowska-Haddal A, Boone KB, Mlikotic A, et al: The structural brain correlates of cognitive deficits in adults with Klinefelter's syndrome. J Clin Endocrinol Metab 91: 1423-1427 (2006).
31. Jacobs PA, Strong JA: A case of human intersexuality having a possible XXY sex-determining mechanism. Nature 183: 302-303 (1959).
32. Kamischke A, Baumgardt A, Horst J, Nieschlag E: Clinical and diagnostic features of patients with suspected Klinefelter syndrome. J Androl 24: 41-48 (2003).
33. Klinefelter HF, Reifenstein EC, Albright F: Syndrome characterized by gynecomastia, aspermatogenesis without Leydigism, increased excretion of follicle stimulating hormone. J Clin Endocrinol 2: 615-627 (1942).
34. Lahlou N, Fennoy I, Carel JC, Roger M: Inhibin B and anti-müllerian hormone, but not testosterone levels, are normal in infants with non-mosaic Klinefelter's syndrome. J Clin Endocrinol Metab 89: 1864-1868 (2004).
35. Lanfranco F, Kamischke A, Zitzmann M, Nieschlag E: Klinefelter's syndrome. Lancet 364: 273-283 (2004).
36. Lue Y, Jentsch JD, Wang C, Rao PN, Hikim AP, et al: XXY mice exhibit gonadal and behavioral phenotypes similar to Klinefelter syndrome. Endocrinology 146: 4148-4154 (2005).
37. Marteau TM, Nippert I, Hall S, Limbert C, Reid M, et al: Decision-making after diagnosis of fetal abnormality. Outcomes of pregnancies diagnosed with Klinefelter syndrome: the possible influence of health professionals. Prenat Diagn 22: 562-566 (2002).
38. McElreavey K, Vilain E, Abbas N, Herskowitz I Fellous M: A regulatory cascade hypothesis for mammalian sex determination: SRY represses a negative regulator of male development. Proc Natl Acad Sci USA 90: 3368-3372 (1993).
39. Nielsen J, Pelsen B, Sørensen K: Follow-up of 30 Klinefelter males treated with testosterone. Clin Genet 33: 262-269 (1988).
40. Patwardhan AJ, Eliez S, Bender B, Linden MG, Reiss AL: Brain morphology in Klinefelter syndrome: extra X chromosome and testosterone supplementation. Neurology 54: 2218-2223 (2000).
41. Patwardhan AJ, Brown WE, Bender BG, Linden MG, Eliez S, et al: Reduced size of the amygdala in individuals with 47,XXY and 47,XXX karyotype. Am J Med Genet 114: 93-98 (2002).
42. Petrone L, Mannucci E, Corona G, Bartolini M, Forti G, et al: Structured interview on erectile dysfunction (SIEDY): a new, multidimensional instrument for quantification of pathogenetic issues on erectile dysfunction. Int J Impot Res 15: 210-220 (2003).
43. Ratcliffe SG: Longitudinal growth studies on children with sex chromosome abnormalities. Prog Clin Biol Res 200: 301-309 (1985).
44. Rose AB, Merke DP, Clasen LS, Rosenthal MA, Wallace GL, et al: Effects of hormones and sex chromosomes on stress-influenced regions of the developing pediatric brain. Ann NY Acad Sci 1032: 231-233 (2004).
45. Ross JL, Roeltgen DP, Stefanatos G, Benecke R, Zeger MP, et al: Cognitive and motor development during childhood in boys with Klinefelter syndrome. Am J Med Genet A 146A:708-719 (2008).
46. Rovenský J: Rheumatic diseases and Klinefelter's syndrome. Autoimmun Rev 6: 33-36 (2006).
47. Salbenblatt JA, Bender BG, Puck MH, Robinson A, Faiman C, et al: Pituitary-gonadal function in Klinefelter syndrome before and during puberty. Pediatr Res 19: 82-86 (1985).
48. Sawalha AH, Harley JB, Scofield RH: Autoimmunity and Klinefelter's syndrome: when men have two X chromosomes. J Autoimmun 33: 31-34 (2009).
49. Sedlmeyer IL, Palmert MR: Delayed puberty: analysis of a large case series from an academic center. J Clin Endocrinol Metab 87: 1613-1620 (2002).
50. Shen D, Liu D, Liu H, Clasen L, Giedd J, et al: Automated morphometric study of brain variation in XXY males. Neuroimage 23: 648-653 (2004).
51. Stemkens D, Roza T, Verrij L, Swaab H, van Werkhoven MK, et al: Is there an influence of X-chromosomal imprinting on the phenotype in Klinefelter syndrome? A clinical and molecular genetic study of 61 cases. Clin Genet 70: 43-48 (2006).
52. Swerdlow AJ, Higgins CD, Schoemaker MJ, Wright AF, Jacobs PA, et al: Mortality in patients with Klinefelter syndrome in Britain: a cohort study. J Clin Endocrinol Metab 90: 6516-6522 (2005).
53. Tajar A, Forti G, O'Neill TW, Lee DM, Silman AJ, et al: Characteristics of secondary, primary, and compensated hypogonadism in aging men: evidence from the European Male Ageing Study. J Clin Endocrinol Metab 95: 1810-1818 (2010).
54. Thomas NS, Hassold TJ: Aberrant recombination and the origin of Klinefelter syndrome. Hum Reprod Update 9: 309-317 (2003).
55. Topper E, Dickerman Z, Prager-Lewin R, Kaufman H, Maimon Z, et al: Puberty in 24 patients with Klinefelter syndrome. Eur J Pediatr 139: 8-12 (1982).
56. Van Assche E, Bonduelle M, Tournaye H, Joris H, Verheyen G, et al: Cytogenetics of infertile men. J Hum Reprod 11 Suppl 4: 1-24 (1996).
57. van Rijn S, Aleman A, Swaab H, Vink M, Sommer I, et al: Effects of an extra X chromosome on language lateralization: an fMRI study with Klinefelter men (47,XXY). Schizophr Res 101: 17-25 (2008).
58. Vierhile A, Robb A, Ryan-Krause P: Attentiondeficit/ hyperactivity disorder in children and adolescents: closing diagnostic, communication, and treatment gaps. J Pediatr Health Care 23 Suppl 1: 5-23 (2009).
59. Vincent MC, Daudin M, De MP, Massat G, Mieusset R, et al: Cytogenetic investigations of infertile men with low sperm counts: a 25-year experience. J Androl 23: 18-22 (2002).
60. Vorona E, Zitzmann M, Gromoll J, Schüring AN, Nieschlag E: Clinical, endocrinological, and epigenetic features of the 46,XX male syndrome, compared with 47,XXY Klinefelter patients. J Clin Endocrinol Metab 92: 3458-3465 (2007).
61. Wikström AM, Dunkel LA : Testicular function in Klinefelter syndrome. Horm Res 69: 317-326 (2008).
62. Yoshida A, Miura K, Nagao K, Hara H, Ishii N, Shirai M: Sexual function and clinical features of patients with Klinefelter's syndrome with the chief complaint of male infertility. Int J Androl 20: 80-85 (1997).
63. Zinn AR, Ramos P, Elder FF, Kowal K, Samango-Sprouse C, et al: Androgen receptor CAGn repeat length influences phenotype of 47,XXY (Klinefelter) syndrome. J Clin Endocrinol Metab 90: 5041-5046 (2005).
64. Zitzmann M, Depenbusch M, Gromoll J, Nieschlag E: X-chromosome inactivation patterns and androgen receptor functionality influence phenotype and social characteristics as well as pharmacogenetics of testosterone therapy in Klinefelter patients. J Clin Endocrinol Metab 89: 6208-6217 (2004).
65. Zollner TM, Veraart JC, Wolter M, Hesse S, Villemur B, et al: Leg ulcers in Klinefelter's syndrome-further evidence for an involvement of plasminogen activator inhibitor-1. Br J Dermatol 136: 341-344 (1997).