Klinefelter syndrome in clinical practice

Abstract

Klinefelter syndrome is the most common sex-chromosome disorder; it affects approximately one in every 660 men. This syndrome is characterized by the presence of one or more extra X chromosomes, and the karyotype 47,XXY is the most prevalent type. The 'prototypic' man with Klinefelter syndrome has traditionally been described as tall, with narrow shoulders, broad hips, sparse body hair, gynecomastia, small testicles, androgen deficiency, azoospermia and decreased verbal intelligence. A less distinct phenotype has, however, been described. Klinefelter syndrome is an underdiagnosed condition; only 25% of the expected number of patients are diagnosed, and of these only a minority are diagnosed before puberty. Patients with Klinefelter syndrome should be treated with lifelong testosterone supplementation that begins at puberty, to secure proper masculine development of sexual characteristics, muscle bulk and bone structure, and to prevent the long-term deleterious consequences of hypogonadism; however, the optimal testosterone regimen for patients with Klinefelter syndrome remains to be established.

Key Points

  • Klinefelter syndrome is the most common sex-chromosome aberration (present in 1 in 660 men), but remains underdiagnosed

  • Common clinical findings in patients with Klinefelter syndrome include small testes (<4 ml), azoospermia, hypergonadotrophic hypogonadism, learning disabilities, gynecomastia, and cryptorchidism

  • Patients with Klinefelter syndrome have an increased risk of developing diabetes, metabolic syndrome, osteoporosis, breast cancer, mediastinal germ-cell tumors and non-Hodgkin's lymphoma

  • Treatment for patients with Klinefelter syndrome can include referral to a speech therapist if necessary (in cases where speech development is delayed) and testosterone treatment from puberty (when gonadotropin levels rise)

  • Infertility in some men with Klinefelter syndrome can be overcome by use of assisted reproduction techniques: testicular sperm extraction and subsequent intracytoplasmatic sperm injection

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Figure 1: The prevalence of postnatal diagnosis of Klinefelter syndrome in Denmark in the year 2000
Figure 2: The vicious circle of hypogonadism, abdominal adiposity and insulin resistance has direct and indirect consequences

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Correspondence to Anders Bojesen.

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A Bojesen declared he has no competing interests.

CH Gravholt has received an honorarium from Novo Nordisk.

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Bojesen, A., Gravholt, C. Klinefelter syndrome in clinical practice. Nat Rev Urol 4, 192–204 (2007). https://doi.org/10.1038/ncpuro0775

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