Introduction: Klinefelter syndrome (KS) represents the most common cause of hypergonadotrophic hypogonadism, with an estimated prevalence of 1:500 to 1:1000 men. This syndrome is characterized by the presence of an additional X chromosome. Eighty percent present with a 47,XXY karyotype and the remaining 20% present with a 47,XXY/46,XY mosaic or with multiple X chromosome aneuploidies, often with additional Y chromosomes. The presence of a 47,XXY/46,XX mosaic with male phenotype and characteristics of KS has been reported in less than a dozen cases. In addition, several other phenotypes associated with this mosaicism have been described including female phenotype or anomaly of ovotesticular sexual differentiation. We report a case of patient with KS phenotype presenting as a 47,XXY/46,XX mosaic discovered while investigating a male primary infertility.
Case presentation: The patient, a 53-year-old house-builder, with a male phenotype and a primary school degree, was referred to the Endocrinology department because of gynecomastia and infertility. He had a history of epilepsy, degenerative discopathy and varicose vein surgery. At the age of 28, he was investigated for infertility. Hypergonadotrophic hypogonadism was detected and a spermogram revealed azoospermia. Due to non-attendance to the appointment he was not supplemented with testosterone. Currently he had no complaints suggestive of hypogonadism. On physical examination he had an eunucoid habitus, a BMI of 23 kg/m2, scarce beard, adipomastia and bilaterally diminished, firm testicles, without masses. Analytically: free testosterone 1.51 pg/ml (6.6030.00), LH 14.0 mIU/ml (1.28.6), FSH 60.9 mIU/ml (1.319.3), hemoglobin 13.5 g/dl (13.916.3), with normal glucose and lipid profile. Testicular ultrasound: diminished testicular volume (right 2.6 ml and left 3.2 ml). Breast ultrasound: adipomastia. Normal bone densitometry. He started supplementation with testosterone 250mg every 3 weeks with normalization of testosterone values. The peripheral blood lymphocytes karyotype revealed mos: 46,XX/47,XXY.
Discussion: KS is not uncommon, but it is often underdiagnosed, possibly because it is not clinically evident until puberty. This diagnosis should be considered in patients with hypergonadotrophic hypogonadism even when discovered in adulthood. The particular aspect of this case is related to the patients karyotype with cell lines 46,XX and 47,XXY. The phenotype in these patients is influenced by the proportion of Y chromosome gonadal cells that is not always the same as in peripheral blood. We have no data regarding the gonadal karyotype in this patient, although, given the phenotype, we suspected that most gonadal cells will contain a Y chromosome, promoting this male sexual differentiation.
18 - 21 May 2019
European Society of Endocrinology