Klinefelter Syndrome Mosaicism 46,XX/47,XXY: A New Case and Literature Review

Chayada Tangshewinsirikul; Wirada Dulyaphat; Thipwimol Tim-Aroon; Rachanee Parinayok; Takol Chareonsirisuthigul; Veerawat Korkiatsakul; Jariya Waisayarat; Pokket Sirisreetreerux; Yada Tingthanatikul; Duangrurdee Wattanasirichaigoon

doi:10.1055/s-0040-1713002

Journal of Pediatric Genetics, Inhaltsverzeichnis

J Pediatr Genet 2020; 09(04): 221-226
DOI: 10.1055/s-0040-1713002

Original Article

Georg Thieme Verlag KG Stuttgart · New York

Klinefelter Syndrome Mosaicism 46,XX/47,XXY: A New Case and Literature Review

Chayada Tangshewinsirikul

¹Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

,

Wirada Dulyaphat

¹Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

,

Thipwimol Tim-Aroon

²Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

,

Rachanee Parinayok

³Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

,

Takol Chareonsirisuthigul

³Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

,

Veerawat Korkiatsakul

³Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

,

Jariya Waisayarat

³Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

,

Pokket Sirisreetreerux

⁴Division of Urology, Department of Surgery, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

,

Yada Tingthanatikul

⁵Division of Reproductive Medicine, Department of Obstetrics and Gynecology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailands

,

Duangrurdee Wattanasirichaigoon

²Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

› Institutsangaben

Abstract

Most cases of Klinefelter syndrome (KS) have 47,XXY karyotype. We reported the first case of 46,XX/47,XXY KS whose genital ambiguity was detected prenatally with postnatal confirmation of the mosaicism and ovotesticular disorder of sex development (OT-DSD). The paternal origin of the extra X chromosome was identified using trio cytogenomic single-nucleotide polymorphism array. Additional 18 cases were also reviewed. The clinical presentation of 46,XX/47,XXY is age-dependent with two age peaks, including ambiguous genitalia during infancy and gynecomastia with or without cyclical hematuria and left scrotal pain and mass in adolescence. The 46,XX is the predominant karyotype both in peripheral blood and gonadal tissue. The risk of germ cell tumor is very high throughout life in these individuals. Individuals with 46,XX/47,XXY mosaicism should be treated more as OT-DSD other than a simple mosaic KS. A multidisciplinary approach and long-term monitoring are necessary.

Keywords

ambiguous genitalia - cyclic hematuria - disorder of sex development - germ cell tumor - left scrotal pain

Volltext

Referenzen

References
1 Radicioni AF, Ferlin A, Balercia G. , et al. Consensus statement on diagnosis and clinical management of Klinefelter syndrome. J Endocrinol Invest 2010; 33 (11) 839-850
2 Lee PA, Houk CP, Ahmed SF, Hughes IA. ; International Consensus Conference on Intersex organized by the Lawson Wilkins Pediatric Endocrine Society and the European Society for Paediatric Endocrinology. Consensus statement on management of intersex disorders. Pediatrics 2006; 118 (02) e488-e500
3 Krob G, Braun A, Kuhnle U. True hermaphroditism: geographical distribution, clinical findings, chromosomes and gonadal histology. Eur J Pediatr 1994; 153 (01) 2-10
4 Low KJ, Abdel-Fattah S, Barton J. , et al. Rare XXY/XX mosaicism in a phenotypic male presenting as cystic hygroma in the first trimester. Clin Dysmorphol 2017; 26 (02) 107-109
5 Cheng WF, Huang SC, Ko TM. Prenatal diagnosis of 46,XX/47,XXY mosaicism: a case report. Prenat Diagn 1995; 15 (01) 64-65
6 Butler LJ, Snodgrass GJ, France NE, Russell A, Swain VA. True hermaphroditism or gonadal intersexuality. Cytogenetic and gonadal analyses of 5 new examples related to 67 known cases studied cytogenetically. Arch Dis Child 1969; 44 (238) 666-680
7 Ozsu E, Mutlu GY, Cizmecioglu FM, Ekingen G, Muezzinoglu B, Hatun S. Ovotesticular disorder of sexual development and a rare 46,XX/47,XXY karyotype. J Pediatr Endocrinol Metab 2013; 26 (7-8): 789-791
8 Mao Y, Chen S, Wang R, Wang X, Qin D, Tang Y. Evaluation and treatment for ovotesticular disorder of sex development (OT-DSD) - experience based on a Chinese series. BMC Urol 2017; 17 (01) 21
9 Tachon G, Lefort G, Puechberty J. , et al. Discordant sex in monozygotic XXY/XX twins: a case report. Hum Reprod 2014; 29 (12) 2814-2820
10 Kanaka-Gantenbein Ch, Papandreou E, Stefanaki K. , et al. Spontaneous ovulation in a true hermaphrodite with normal male phenotype and a rare 46,XX/47,XXY Klinefelter's mosaic karyotype. Horm Res 2007; 68 (03) 139-144
11 Bergmann M, Schleicher G, Böcker R, Nieschlag E. True hermaphroditism with bilateral ovotestis: a case report. Int J Androl 1989; 12 (02) 139-147
12 Isguven P, Yildiz M, Arslanoglu I, Adal E, Erguven M, Tuzlali S. True hermaphroditism with characteristics of Klinefelter's syndrome: a rare presentation. J Pediatr Endocrinol Metab 2005; 18 (06) 603-606
13 Chouhan JD, Chu DI, Birs A. , et al. Ovotestis in adolescence: 2. Urology 2017; 105: 171-174
14 Pérez-Palacios G, Carnevale A, Escobar N, Villareal G, Fernandez C, Medina M. Induction of ovulation in a true hermaphrodite with male phenotype. J Clin Endocrinol Metab 1981; 52 (06) 1257-1259
15 Talreja SM, Banerjee I, Yadav SS, Tomar V. A rare case of lateral ovotesticular disorder with Klinefelter syndrome mosaicism 46, XX/47, XXY: an unusual presentation. Urol Ann 2015; 7 (04) 520-523
16 Torres L, López M, Méndez JP. , et al. Molecular analysis in true hermaphrodites with different karyotypes and similar phenotypes. Am J Med Genet 1996; 63 (02) 348-355
17 Song JS, Lee SH, Jin DK, Kim SH. A case report of rare XXY/XX mosaicism in a phenotypic male with Klinefelter syndrome and mediastinal germ cell tumor. Genet Couns 2014; 25 (02) 215-220
18 Hamlett JD, Timson J, Harris R. XX-XXY mosaicism in a phenotypically normal female. Hum Hered 1970; 20 (03) 260-264
19 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; 49 (04) 331-337
20 Matsuki S, Sasagawa I, Kakizaki H, Suzuki Y, Nakada T. Testicular teratoma in a man with XX/XXY mosaic Klinefelter's syndrome. J Urol 1999; 161 (05) 1573-1574
21 Thomas NS, Hassold TJ. Aberrant recombination and the origin of Klinefelter syndrome. Hum Reprod Update 2003; 9 (04) 309-317
22 Martin CL, Ruble DN, Szkrybalo J. Cognitive theories of early gender development. Psychol Bull 2002; 128 (06) 903-933
23 Jaruratanasirikul S, Engchaun V. Management of children with disorders of sex development: 20-year experience in southern Thailand. World J Pediatr 2014; 10 (02) 168-174
24 Williams LA, Pankratz N, Lane J. , et al. Klinefelter syndrome in males with germ cell tumors: a report from the Children's Oncology Group. Cancer 2018; 124 (19) 3900-3908
25 Mukerjee D, Bowen J, Anderson DE. Simian papovavirus 40 transformation of cells from cancer patient with XY-XXY mosaic Klinefelter's syndrome. Cancer Res 1970; 30 (06) 1769-1772