Novel Approaches in the Management of Klinefelter Syndrome

  • Fnu DeepinderEmail author


Klinefelter syndrome is the most common form of hypogonadism in men and is the leading genetic cause of male infertility. It also represents the most prevalent chromosomal aneuploidy in human beings. It is characterized by the presence of an extra X chromosome in a phenotypic male. The most abundant karyotype is 47, XXY, although other patterns including mosaicism (47, XY/47, XXY) and higher grade chromosomal aneuploidies containing supranumerous X chromosomes (48, XXXY, 49, XXXXY) are not uncommon. The latter phenotypes are more severely affected in terms of physical and mental development than men with classic 47, XXY karyotypes. The genetic cause is either from meiotic nondisjunction leading to failure of separation of the chromosome pair during the first or second division of gametogenesis or from mitotic nondisjunction in the developing zygote. Increasing maternal age has been reported to raise the risk of Klinefelter syndrome. The estimated prevalence of Klinefelter syndrome in men is 1:500 or 0.1–0.2% of the general population. However, extremely large discrepancies have been reported between prenatal and postnatal prevalence suggesting high rates of under diagnosis. A large Danish national registry study observed only 25% of the expected patients diagnosed after birth, and less than 10% of the expected diagnoses were made before puberty. Some of the major reasons for this underdiagnosis are thought to be the variable phenotype of Klinefelter syndrome and low awareness of the disease among medical professionals. Recognition of clinical features is hence important for early detection of this syndrome.


Klinefelter syndrome Chromosomal aneuploidy Hypogonadism 47, XXY karyotypes Osteoporosis Incomplete pubertal development Mosaicism Barr-body analysis 


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of Endocrinology, Diabetes and MetabolismCedars Sinai Medical CenterLos AngelesUSA

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