Klinefelter's syndrome: a clinical and therapeutical update

The prevalence of the Klinefelter's syndrome, ranging between 1/500 and 1/1,000 in the general male population, rises up to 3-4% among infertile males and to 10-12% in azoospermic patients. Due to the paucity of symptoms, only 10% of Klinefelter patients are diagnosed prepubertally. The clinical spectrum of the phenotype of adult Klinefelter patients is very broad and ranges from clinically overt hypogonadism to normally virilized males. The diagnosis is usually made during the evaluation of couple infertility. The only nearly constant clinical feature is the reduced testicular volume and azoospermia or, in few cases, cryptozoospermia. Due to the variability of the phenotype and also to the fact that the main symptoms of the syndrome (androgen deficiency, infertility) are in the reproductive domain, approximately two thirds of Klinefelter patients are not diagnosed during their life. Low/normal testosterone and high levels of the luteinizing hormone (LH) suggest that all Klinefelter patients have overt or compensated hypogonadism which should be treated with testosterone, starting from the peri-pubertal age. Even if no medical treatment is possible for infertility, testicular sperm for assisted reproduction techniques can be obtained by multiple testicular biopsies in experienced centers in up to 50% of subjects. Although there are no predictors for successful sperm retrieval, the birth of 101 children with normal karyotype was reported in the last 15 years. Furthermore, the genetic risk to the offspring of Klinefelter patients has recently not been found to be greater than that of patients with nonobstructive azoospermia with normal karyotype.