Klinefelter syndrome is an abnormality of sexual development which is usually characterised by the chromosome complement of 47,XXY, although occasionally patients may have multiple X or Y chromosomes, may be mosaic with 46, XY, 47,XXY or have an X-autosome translocation. We present the case of a 43 year old male patient with the phenotypic appearance of Klinefelter syndrome and primary infertility, who was found on karyotype analysis to have an hitherto undescribed inversion of the long arm of the X chromosome 46 Y, inv (X) (q12q24). FISH analysis demonstrated that the proximal breakpoint did not involve the androgen receptor and was further proximal to it. The underlying genetic mechanisms responsible for his phenotype remain unknown, but may include abnormal expression of X chromosome genes caused by abnormal X inactivation, a cytogenetically undetectable deletion of the X chromosome genes around the breakpoint (s) and/or impairment of normal chromosome pairing at meiosis. The patient has responded well to androgen replacement therapy.
03 - 04 Dec 2001
Society for Endocrinology