45,X/46,XY Mosaicism in an 18-year-old Girl with Primary Amenorrhea

A Case Report

Keywords: Mixed gonadal dysgenesis, Turner syndrome, Y chromosome, sex chromosome aberrations, 45X/46XY mosaicism

Abstract

45,X/46,XY mosaicism is a rare disorder with a wide heterogeneity in its manifestations. An 18-year-old girl was referred to the endocrine clinic for investigation of her primary amenorrhea. Clinical examination was unremarkable. Hormonal profile was consistent with primary ovarian insufficiency and human chorionic gonadotropin (hCG) stimulation did not show evidence of active testicular tissue. Karyotyping studies by G-banding revealed a 45,X/46,XY karyotype.
She was diagnosed with mosaic Turner syndrome with Y chromosomal material and investigation was performed to identify the presence of male gonads due to the risk of gonadal malignancy. Magnetic resonance imaging (MRI) of the pelvis did not show evidence of gonads. Laparoscopic exploration was proposed but the patient and parents refused opting for conservative management. This case highlights the challenges in the management of this rare condition.

Downloads

Download data is not yet available.

Author Biographies

Eunice Yi Chwen Lau, Hospital Queen Elizabeth II

Division of Endocrinology, Department of Medicine

Yin Khet Fung, Hospital Queen Elizabeth II

Division of Endocrinology, Department of Medicine

References

Lee PA, Houk CP, Ahmed SF, et al. Consensus statement on management of intersex disorders. International Consensus Conference on Intersex. Pediatrics. 2006;118(2):e488-500. https://www.ncbi.nlm.nih.gov/pubmed/16882788. https://doi.org/10.1542/peds.2006-0738.

McCann-Crosby B, Mansouri R, Dietrich JE, et al. State of the art review in gonadal dysgenesis: Challenges in diagnosis and management. Int J Pediatr Endocrinol. 2014;2014(1):4. https://www.ncbi.nlm.nih.gov/pubmed/24731683. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3995514. https://doi.org/10.1186/1687-9856-2014-4.

MacLaughlin DT, Donahoe PK. Sex determination and differentiation.

N Eng J Med. 2004;350(4):367-78. https://www.ncbi.nlm.nih.gov/pubmed/14736929. https://doi.org/10.1056/NEJMra022784.

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. https://www.ncbi.nlm.nih.gov/pubmed/2294747. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1683543.

Sallai A, Sólyom J, Dobos M, et al. Y-chromosome markers in Turner syndrome: Screening of 130 patients. J Endocrinol Investig. 2010;33(4):222–7. https://www.ncbi.nlm.nih.gov/pubmed/19625757. https://doi.org/10.1007/BF03345783.

Knauer-Fischer S, Besikoglu B, Inta I, Kneppo C, Vogt PH, Bettendorf M. Analyses of gonadoblastoma Y (GBY)-locus and of Y centromere in Turner syndrome patients. Experimental Clin Endocrinol Diab. 2015;123(1):61–5. https://www.ncbi.nlm.nih.gov/pubmed/25314650. https://doi.org/10.1055/s-0034-1387734.

Wu Q, Wang C, Shi H, Kong X, Ren S, Jiang M. The clinical manifestation and genetic evaluation in patients with 45,X/46,XY mosaicism. Sex Dev. 2017; 11(2):64-9. https://www.ncbi.nlm.nih.gov/pubmed/28214852. https://doi.org/10.1159/000455260.

Gravholt CH, Andersen NH, Conway GS, et al. Clinical practice guidelines for the care of girls and women with Turner syndrome: Proceedings from the 2016 Cincinnati International Turner Syndrome Meeting. Eu J Endocrinol. 2017;177(3):G1-70. https://www.ncbi.nlm.nih.gov/pubmed/28705803. https://doi.org/10.1530/EJE-17-0430.

Pleskacova J, Hersmus R, Oosterhuis JW, et al. Tumor risk in disorders of sex development. Sex Dev. 2010;4(4-5):259–69. https://www.ncbi.nlm.nih.gov/pubmed/20558977. https://doi.org/10.1159/000314536.

Hatano M, Fukuzawa R, Hasegawa Y. The mosaicism ratio of 45,X may explain the phenotype in a case of mixed gonadal dysgenesis. Sex Dev. 2018;12(4):175-9. https://www.ncbi.nlm.nih.gov/pubmed/29879705. https://doi.org/10.1159/000489451.

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. https://www.ncbi.nlm.nih.gov/pubmed/21508138. https://doi.org/10.1210/jc.2011-0232.

Scully RE. Gonadoblastoma: A review of 74 cases. Cancer. 1970;25(6):1340–56. https://www.ncbi.nlm.nih.gov/pubmed/4193741.https://doi.org/10.1002/1097-0142(197006)25:6<1340::aid-cncr2820250612>3.0.co;2-n.

Cools M, Drop SL, Wolffenbuttel KP, Oosterhuis JW, Looijenga LH. Germ cell tumors in the intersex gonad: Old paths, new directions, moving frontiers. Endocr Rev. 2006; 27(5):468–84. https://www.ncbi.nlm.nih.gov/pubmed/16735607. https://doi.org/10.1210/er.2006-0005.

Hasle H, Olsen JH, Nielsen J, Hansen J, Friedrich U, Tommerup N. Occurrence of cancer in women with Turner syndrome. Br J Cancer. 1996;73(9):1156–9. https://www.ncbi.nlm.nih.gov/pubmed/8624281. https://www.ncbi.nlm.nih.gov/pmc/articles/

PMC2074404. https://doi.org/10.1038/bjc.1996.222.

Gravholt CH, Fedder J, Naeraa RW, Muller J. Occurrence of gonadoblastoma in females with Turner syndrome and Y chromosome material: A population study. J Clin Endocrinol Metabol. 2000;85(9):3199–202. https://www.ncbi.nlm.nih.gov/pubmed/10999808. https://doi.org/10.1210/jcem.

9.6800.

Alaniz VI, Kobernik EK, Dillman J, Quint EH. Utility of ultrasound and magnetic resonance imaging in patients with disorders of sex development who undergo prophylactic gonadectomy. J Pediatr Adolesc Gynecol. 2016;29(6):577-81. https://www.ncbi.nlm.nih.gov/pubmed/27079912. https://doi.org/10.1016/j.jpag.2016.03.007.

Steven M, O’Toole S, Lam JPH, MacKinlay GA, Cascio S. Laparoscopy versus ultrasonography for the evaluation of Mullerian structures in children with complex disorders of sex development. Pediatr Surg Int. 2012; 28(12):1161–4. https://www.ncbi.nlm.nih.gov/pubmed/23064803. https://doi/org/10.1007/s00383-012-3178-3.

Ebert KM, Hewitt GD, Indyk JA, McCracken KA, Nahata L, Jayanthi VR. Normal pelvic ultrasound or MRI does not rule out neoplasm in patients with gonadal dysgenesis and Y chromosome material. J Pediatr Urol. 2018;14(2):154.e1-6. https://www.ncbi.nlm.nih.gov/pubmed/29317190. https://doi.org/10.1016/j.jpurol.2017.11.009.

Zalel Y, Piura B, Elchalal U, Czernobilsky B, Antebi S, Dgani R. Diagnosis and management of malignant germ cell ovarian tumors in young females. Int J Gynaecol Obstet. 1996;55(1):1-10. https://www.ncbi.nlm.nih.gov/pubmed/8910077. https://doi.org/10.1016/0020-7292(96)02719-1.

Published
2020-04-20
How to Cite
Lau, E. Y. C., & Fung, Y. K. (2020). 45,X/46,XY Mosaicism in an 18-year-old Girl with Primary Amenorrhea: A Case Report. Journal of the ASEAN Federation of Endocrine Societies, 35(1). Retrieved from https://asean-endocrinejournal.org/index.php/JAFES/article/view/749