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, 40 (2), 123-134

Klinefelter Syndrome (KS): Genetics, Clinical Phenotype and Hypogonadism

Collaborators, Affiliations

Klinefelter Syndrome (KS): Genetics, Clinical Phenotype and Hypogonadism

M Bonomi et al. J Endocrinol Invest.


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.

Keywords: Azoospermia; Chromosome abnormalities; Hypergonadotropic hypogonadism; KS; Klinefelter syndrome; Male infertility; Testosterone.

Conflict of interest statement

MB, VR, DP, GB; AF declare that they have no conflict of interest. EAJ has been speaker or consultant for Bayer, Bracco, GSK, Ibsa, Pfizer, Menarini, and Shionogi. Ethical approval This article does not contain any studies with human participants or animals performed by the authors. Informed consent Formal consent is not required.


Fig. 1
Fig. 1
Signs and symptoms of KS according to the severity of clinical phenotype
Fig. 2
Fig. 2
The broad spectrum of phenotypes in KS depends on the severity of all its components (number of supernumerary X chromosome, genetic impact of supernumerary X, severity of hypogonadism) as well as on the time duration of the disease, the delay in the diagnosis of testosterone deficiency, and advancing age coupled with increasing other comorbidities

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