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

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

Authors' Contributions

C.T. designed the study, collected clinical data, performed literature review, and wrote the manuscript. W.D., T.T., P.S., and Y.T. provided clinical data and/or surgical specimens. R.P., T.C., and V.K. performed and analyzed genetic testing. J.W. reviewed histology and D.W. supervised overall concept design and edited the manuscript. All the authors reviewed the manuscript.

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