Klinefelter's syndrome

Last reviewed 08/2021

Klinefelter’s syndrome (KS) was first described by Harry Klinefelter in 1942 as an endocrine disorder of unknown etiology. In 1959, Jacobs et al recognized KS as a chromosomal disorder in which the patients had an extra X chromosome to a normal male karyotype, 46 XY (1).

• the most common karyotype is 47 XXY which is considered to be the classic form of the disease (1)
• also it is not uncommon to find patients with
  • sex chromosomal aneuploidies e.g. - 48,XXYY; 48,XXXY and 49,XXXXY. These men usually have similar but often more severe phenotypes than those with the XXY karyotype (3)
• mosaicism, a mixture of both normal and 47 XXY cells or mixtures of   47 XXY and other karyotypes (2). A milder phenotype is usually seen in these patients (3)

• phenotype of KS is relatively mild when compared to that of other autosomal trisomies (e.g., Down syndrome) (2) since the additional X chromosome is predominantly inactivated (but the entire X chromosome is not inactivated.)
• increase in phenotypic severity is seen when the number of X chromosomes increases (3)

This is the most common cause of male hypogonadism. Majority of patients are undiagnosed due to non specific clinical findings while in some cases, diagnosis is made post mortem (4).   

Increased maternal age is linked with an increased risk of having a child with KS (2). Affected individuals have a normal life span.

Reference:

• (1) Visootsak J, Graham JM Jr. Klinefelter syndrome and other sex chromosomal aneuploidies. Orphanet J Rare Dis. 2006;1:42.  
• (2) Bojesen A, Gravholt CH. Klinefelter syndrome in clinical practice. Nat Clin Pract Urol. 2007;4(4):192-204.  
• (3) Wattendorf DJ, Muenke M. Klinefelter syndrome. Am Fam Physician. 2005;72(11):2259-62.  
• (4) Verri A et al. Klinefelter's syndrome and psychoneurologic function. Mol Hum Reprod. 2010;16(6):425-33.