Klinefelter syndrome (KS): genetics, clinical phenotype and hypogonadism

Bonomi M; Rochira V; Pasquali D; Balercia G; Jannini EA; Ferlin A; Klinefelter ItaliaN Group (KING)

doi:10.1007/s40618-016-0541-6

Genetics and Immunology Reproductive Genetics

Klinefelter syndrome (KS): genetics, clinical phenotype and hypogonadism

Bonomi M, Rochira V, Pasquali D, Balercia G, Jannini EA, Ferlin A, Klinefelter ItaliaN Group (KING)

Published February 2017 Journal of endocrinological investigation

DOI 10.1007/s40618-016-0541-6 PMID 27644703 PMC PMC5269463

RRM Academy Synopsis

Klinefelter syndrome varies widely in severity and is often missed

Klinefelter syndrome, an extra X chromosome in men, ranges from mild to severe. This 2017 narrative review from the Klinefelter ItaliaN Group describes its genetic causes and clinical features. Most men with the syndrome remain undiagnosed, the authors write.

Key Findings

The syndrome affects 0.1 to 0.2 % of newborn male infants, up to 3–4 % of infertile males and up to 10–12 % of azoospermic patients (no sperm in semen).
About 80–90 % of cases carry the classic 47,XXY karyotype. The remaining cases, approximately 10–20 %, include more than one extra sex chromosome, a structurally abnormal X chromosome or mosaicism.
Errors in chromosome separation during egg or sperm formation appear equally distributed between mothers and fathers among patients, at nearly 50 % each.
Cases were 4-fold more prevalent with mothers aged >40 years than with mothers aged <24.
Serum testosterone below normal occurs in 65–85 % of adults with the syndrome. After age 25, about 80 % report symptoms of overt hypogonadism, such as decreased libido.

Interpretation

Testosterone replacement is effective for symptoms of androgen deficiency, the review states. The authors note that psychiatric findings linked to the syndrome, such as depression and autistic traits, need replication on a larger scale. The findings support further research into the syndrome's full range of clinical features.

RRM Context

Restorative reproductive medicine evaluates both partners and looks for the cause of infertility. Klinefelter syndrome is one named cause on the male side. The review states that most cases remain undiagnosed, and some men with no sperm in the semen carry the condition.

Our editorial summary of this paper, not the article's abstract.

Abstract

Klinefelter Syndrome (KS) is characterized by an extreme heterogeneity in its clinical and genetic presentation. The relationship between clinical phenotype and genetic background has been partially disclosed; nevertheless, physicians are aware that several aspects concerning this issue are far to be fully understood. By improving our knowledge on the role of some genetic aspects as well as on the KS, patients' interindividual differences in terms of health status will result in a better management of this chromosomal disease. The aim of this review is to provide an update on both genetic and clinical phenotype and their interrelationships.

Topics

Genetics and Immunology

Reproductive Genetics Chromosomal Abnormalities

Genetics and Immunology › Reproductive Genetics › Chromosomal Abnormalities

PMID 27644703 27644703 DOI 10.1007/s40618-016-0541-6 10.1007/s40618-016-0541-6 Bonomi et al. 2017, Bonomi 2017

Klinefelter syndrome (KS): genetics, clinical phenotype and hypogonadism

Klinefelter syndrome varies widely in severity and is often missed

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

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