Genetics

The disease is characterized by the presence of an extra X chromosome and a single ‘Y’ chromosome in a phenotypic male (1).

• the most common karyotype is 47 XXY - around 80-90% of KS cases show this classic karyotype
• other sex chromosome variants are less common e.g. -
  • mosaicism - e.g. 47,XXY/46,XY
  • other sex chromosomal aneuploidies e.g. -
    • 48,XXYY and 48,XXXY - seen in 1 per 17,000 to 1 per 50,000 male births
    • 49,XXXXY - seen in 1 per 85,000 to 100,000 male births (2)

This additional sex chromosome in men is a result of meiotic nondisjunction in either the first or the second meiotic division (caused by abnormal separation of chromosomes or chromatids during the process of meiosis) (1)

• the supplementary X chromosome is of
  • paternal origin in 50 to 60%
  • maternal origin in 40 to 50% of cases (3)

Reference:

• (1) Bojesen A, Gravholt CH. Klinefelter syndrome in clinical practice. Nat Clin Pract Urol. 2007;4(4):192-204.
• (2) Tüttelmann F, Gromoll J. Novel genetic aspects of Klinefelter's syndrome. Mol Hum Reprod. 2010;16(6):386-95.
• (3) Wattendorf DJ, Muenke M. Klinefelter syndrome. Am Fam Physician. 2005;72(11):2259-62.