Klinefelter syndrome (47,XXY) has a prevalence of approximately 1 in 500 males. It is a condition characterized by an extra X chromosome and is an underdiagnosed clinical entity. Inactivation of genes enables their escape from regulatory mechanisms, which can result in such classic physical manifestations as hypogonadism, gynecomastia, infertility, and various hormonal and physical abnormalities. While the endocrine manifestations of 47,XXY are well-known, the oncologic manifestations have received less attention. An association between cancer and 47,XXY has not as yet been clearly defined, with variability noted in the prevalence of different malignancies in 47,XXY patients. The mechanisms underlying these altered oncologic risks are still under debate. Some of the proposed explanations include hormone imbalance, developmental malfunctions, and failed DNA repair mechanisms. However, the recognition of the oncological associations linked to 47,XXY could be helpful. Screening measures in certain malignancies may enable an earlier diagnosis of 47,XXY and the implementation of more customized care in 47,XXY and the mosaic variants.. The data for this review was compiled from relevant PubMed articles published within the last three decades and organized based on cancer type.
Keywords: Cancer; Karyotyping; Klinefelter syndrome; Underdiagnosis.