New Perspectives in Klinefelter Syndrome

Histopathology of the testes in Klinefelter syndrome (KS) (47, XXY-no mosaicism) is characterized by complete fibrosis and hyalinization of seminiferous tubules, resulting in azoospermia and failure of fatherhood. This occurs through a gradual process that begins in the fetus, progresses through infancy and accelerates dramatically at the time of puberty. But recently with amniocentesis and study of aborted fetuses in different stages, seminiferous tubules showed germ cells. Therefore, new salvages have been undertaken recently for gonosomes in these patients. One method involves cryopreservation of sperms in school-age boys at the age of 11 - 15 years having testicular volumes between 2 - 4 ml. Another salvage process attempts to pick patients with low-grade mosaicism who may have normal cell line and isolated foci of spermatogenesis in their seminiferous tubules. This is done by analyzing 150 well-spread G-banded metaphases instead of the usual 20 or less metaphase spreads and increasing the number of cells analyzed either by karyotyping or by FISH in interphase nuclei. This is a good marker for intracytoplasmic sperm injection. Another complication of KS is precocious osteoporosis which was believed to be due only to early onset of testosterone deficiency. However, reduced bone mass might be present also in KS men with normal testosterone levels and even with testosterone replacement therapy. Possible new determinants for osteoporosis in KS might be related to the androgen receptor (AR) function and insulin-like factor 3 (INSL3) levels.