45,X/46,XY mosaicism
report on 14 patients from a Brazilian hospital. A retrospective study
Keywords:
Genitalia, Mosaicism, Turner syndrome, Azoospermia, NeoplasmsAbstract
CONTEXT AND OBJECTIVE: 45,X/46,XY mosaicism, or mixed gonadal dysgenesis, is considered to be a rare disorder of sex development. The aim of our study was to investigate the clinical and cytogenetic characteristics of patients with this mosaicism. DESIGN AND SETTING: A retrospective study in a referral hospital in southern Brazil. METHODS: Our sample consisted of patients diagnosed at the clinical genetics service of a referral hospital in southern Brazil, from 1975 to 2012. Clinical and cytogenetic data were collected from the medical records. RESULTS: Fourteen patients were included in the sample, with ages at the first evaluation ranging from 2 days to 38 years. Nine of them had female sex of rearing and five, male. Regarding the external genitalia, most were ambiguous (n = 10). One patient presented male phenotype and was treated for a history of azoospermia, while three patients presented female phenotype, of whom two had findings of Turner syndrome and one presented secondary amenorrhea alone. Some findings of Turner syndrome were observed even among patients with ambiguous genitalia. None presented gonadal malignancy. One patient underwent surgical correction for genital ambiguity and subsequent exchange of sex of rearing. Regarding cytogenetics, we did not observe any direct correlation between percentages of cell lines and phenotype. CONCLUSIONS: 45,X/46,XY mosaicism can present with a wide variety of phenotypes resulting from the involvement of different aspects of the individual. All these observations have important implications for early recognition of these patients and their appropriate management.
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References
Hughes IA. Disorders of sex development: a new definition and classification. Best Pract Res Clin Endocrinol Metab. 2008;22(1):119-34.
Telvi L, Lebbar A, Del Pino O, Barbet JP, Chaussain JL. 45,X/46,XY mosaicism: report of 27 cases. Pediatrics. 1999;104(2 Pt 1):304-8.
Hamerton JL, Canning N, Ray M, Smith S. A cytogenetic survey of 14,069 newborn infants. I. Incidence of chromosome abnormalities. Clin Genet. 1975;8(4):223-43.
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. International Consensus Conference on Intersex. Pediatrics. 2006;118(2):e488-500.
Ahmed SF, Khwaja O, Hughes IA. The role of a clinical score in the assessment of ambiguous genitalia. BJU Int. 2000;85(1):120-4.
Cools M, Pleskacova J, Stoop H, et al. Gonadal pathology and tumor risk in relation to clinical characteristics in patients with 45,X/46,XY mosaicism. J Clin Endocrinol Metab. 2011;96(7):E1171-80.
Rosenberg C, Frota-Pessoa O, Vianna-Morgante AM, Chu TH. Phenotypic spectrum of 45,X/46,XY individuals. Am J Med Genet. 1987;27(3):553-9.
Knudtzon J, Aarskog D. 45,X/46,XY mosaicism. A clinical review and report of ten cases. Eur J Pediatr. 1987;146(3):266-71.
Gantt PA, Byrd JR, Greenblatt RB, McDonough PG. A clinical and cytogenetic study of fifteen patients with 45,X/46,XY gonadal dysgenesis. Fertil Steril. 1980;34(3):216-21.
Wheeler M, Peakman D, Robinson A, Henry G. 45,X/46,XY mosaicism: contrast of prenatal and postnatal diagnosis. Am J Med Genet. 1988;29(3):565-71.
Chang HJ, Clark RD, Bachman H. The phenotype of 45,X/46,XY mosaicism: an analysis of 92 prenatally diagnosed cases. Am J Hum Genet. 1990;46(1):156-67.
Reddy KS, Sulcova V. Pathogenetics of 45,X/46,XY gonadal mosaicism. Cytogenet Cell Genet. 1998;82(1-2):52-7.
Tosson H, Rose SR, Gartner LA. Description of children with 45,X/46,XY karyotype. Eur J Pediatr. 2012;171(3):521-9.
Costa T, Lambert M, Teshima I, et al. Monozygotic twins with 45,X/46,XY mosaicism discordant for phenotypic sex. Am J Med Genet. 1998;75(1):40-4.
Tho SP, Jackson R, Kulharya A, et al. Long-term follow-up and analysis of monozygotic twins concordant for 45,X/46,XY peripheral blood karyotype but discordant for phenotypic sex. Am J Med Genet Part A. 2007;143A(21):2616-22.
Verp MS, Simpson JL. Abnormal sexual differentiation and neoplasia. Cancer Genet Cytogenet. 1987;25(2):191-218.
Hsu LY. Prenatal diagnosis of 45,X/46,XY mosaicism--a review and update. Prenat Diagn. 1989;9(1):31-48.
Alvarez-Nava F, Gonzalez S, Soto M, Pineda L, Morales-Machin A. Mixed gonadal dysgenesis: a syndrome of broad clinical, cytogenetic and histopathologic spectrum. Genet Couns. 1999;10(3):233-43.
Penna Videaú SP, Araujo H, Ballesta F, Ballescá JL, Vanrell JA. Chromosomal abnormalities and polymorphisms in infertile men. Arch Androl. 2001;46(3):205-10.
Gassó-Matoses M, Picó-Alfonso A, Fernández-Garcia J, Lobato- Encinas J, Mira-Llinares A. 45,X/46,XY gonadal dysgenesis in an infertile adult male. Urol Int. 1992;48(2):239-41.
Alvarez-Nava F, Puerta H. Y-chromosome microdeletions in 45,X/46,XY patients. Am J Med Genet Part A. 2006;140(10):1128-30.
Aarskog D. Intersex conditions masquerading as simple hypospadias. Birth Defects Orig Artic Ser. 1971;7(6):122-30.
Lindhardt Johansen M, Hagen CP, Rajpert-De Meyts E, et al. 45,X/46,XY mosaicism: phenotypic characteristics, growth, and reproductive function--a retrospective longitudinal study. J Clin Endocrinol Metab. 2012;97(8):E1540-9.
Aranoff GS, Morishima A. X0/XY mosaicism in delayed puberty. J Adolesc Health Care. 1988;9(6):501-4.
Lara Orejas E, Golmayo Gaztelu LG, Núñez Estevez M, et al. Talla baja em varones con fenotipo normal y mosaicismo 45,X/46,XY [Low stature in males with normal phenotype and 45,X/46,XY mosaicism]. An Pediatr (Barc). 2008;68(2):140-2.
Tosson H, Rose SR, Gartner LA. Children with 45,X/46,XY karyotype from birth to adult height. Horm Res Paediatr. 2010;74(3):190-200.
Richter-Unruh A, Knauer-Fischer S, Kaspers S, et al. Short stature in children with an apparently normal male phenotype can be caused by 45,X/46,XY mosaicism and is susceptible to growth hormone treatment. Eur J Pediatr. 2004;163(4-5):251-6.
Méndez JP, Ulloa-Aguirre A, Kofman-Alfaro S, et al. Mixed gonadal dysgenesis: clinical, cytogenetic, endocrinological, and histopathological findings in 16 patients. Am J Med Genet. 1993;46(3):263-7.
Simpson JL, Elias S. Genetics in obstetrics and Gynecology. Philadelphia: Saunders; 2003.
Bianchi DW, Crobleholme TM, D’Alton ME. Fetology. Diagnosis and management of the fetal patient. New York: McGraw-Hill Co; 2000.
Jiao X, Qin C, Li J, et al. Cytogenetic analysis of 531 Chinese women with premature ovarian failure. Hum Reprod. 2012;27(7):2201-7.
Cools M, Drop SL, Wolffenbuttel KP, Oosterhuis JW, Looijenga LH. Germ cells tumors in the intersex gonad: old paths, new directions, moving frontiers. Endocr Rev. 2006;27(5):468-84.
Maciel-Guerra AT, Guerra Júnior. Menino ou menina? Distúrbios da diferenciação do sexo. 2a ed. Rio de Janeiro: Editora Rubio; 2010.
