Klinefelter Syndrome

Klinefelter syndrome (KS) is the most common sex chromosome aneuploidy in males, occurring in approximately 1 in 500 to 1 in 1000 live male births. It results from the presence of one or more extra X chromosomes, with the classic karyotype being 47,XXY (present in approximately 80-90 percent of cases). Variant karyotypes include 48,XXXY, 48,XXYY, 49,XXXXY, and mosaic forms (46,XY/47,XXY) where some cells have a normal male karyotype and others carry the extra X chromosome. The mosaic form tends to present with milder clinical features because a proportion of cells function normally. The condition arises from nondisjunction during parental meiosis -- the failure of the sex chromosomes (either maternal XX or paternal XY pair) to separate properly during cell division, resulting in a gamete with an extra sex chromosome. Risk factors for nondisjunction include advanced maternal age, though Klinefelter syndrome can occur regardless of parental age. The extra X chromosome is largely inactivated (X-inactivation or lyonization) in each cell, similar to the process in typical females, but some genes on the X chromosome escape inactivation and are expressed from both...