Klinefelter syndrome and cancer
Klinefelter syndrome, also referred to as XXY syndrome or 47,XXY syndrome, is a genetic condition arising from the presence of an extra X chromosome in males, leading to various physical and hormonal manifestations. Individuals with this syndrome typically experience symptoms such as infertility, small testes, gynecomastia (enlarged breasts), and other health issues, including an increased risk of certain cancers. Notably, while the overall cancer incidence among those with Klinefelter syndrome does not differ significantly from that of the general male population, specific types of cancer, such as male breast cancer, non-Hodgkin lymphoma, and germ-cell tumors, are more prevalent in these individuals.
Testosterone hormone replacement therapy, often used to manage symptoms of Klinefelter syndrome, can elevate the risk of prostate cancer. Diagnosis generally requires cytogenetic analysis, which may occur during investigations for infertility or other health conditions. Treatment options focus on alleviating symptoms, supporting reproductive efforts, and monitoring for increased cancer risks. Although Klinefelter syndrome is a lifelong condition, early diagnosis and appropriate management can lead to a normal life expectancy and quality of life. Awareness and screening for associated cancers are essential for individuals with this syndrome.
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Klinefelter syndrome and cancer
ALSO KNOWN AS: Klinefelter’s syndrome, XXY syndrome, 47,XXY syndrome
RELATED CONDITIONS: Breast, prostate, and lung cancer; non-Hodgkin lymphoma; extragonadal (often mediastinal) germ-cell tumors; testicular tumors (such as germinoma)
DEFINITION: Klinefelter syndrome is a condition caused by an extra sex chromosome (usually 47,XXY) that results in a phenotypic man with several characteristic manifestations.
Risk factors: The risks of certain cancers are increased in Klinefelter's syndrome. Klinefelter patients given testosterone hormone replacement therapy increase their risk of prostate cancer.
Etiology and the disease process: The XXY chromosome arrangement disrupts normal testicular development, leading to impaired sex hormone production. This is the etiology of many symptoms of Klinefelter's syndrome. Klinefelter patients are sterile because of seminiferous tubule dysgenesis. Genes not related to sex on the X chromosome may cause other manifestations.
Incidence: Klinefelter's syndrome occurs in 1 in 500 to 1 in 1,000 newborn male children. The overall incidence of all malignancies in patients with Klinefelter's syndrome is not significantly different from the incidence among men with normal male chromosomes. However, certain types of cancer are more common among Klinefelter patients than 46,XY (so-called normal) men. These include male breast cancer, non-Hodgkin lymphoma, extragonadal (often mediastinal) teratomas, germ-cell tumors of the testes, and possibly lung cancer, gallbladder cancer, and extrahepatic bile duct tumors. Prostate cancer risk is very low unless hormone therapy with testosterone is initiated; then, the risk for adenocarcinoma of the prostate is increased.
Symptoms: Klinefelter patients typically have small, atrophic testes (microorchidism), infertility, a small penis, gynecomastia (enlarged breasts), tall stature, truncal obesity, autoimmune disorders, diabetes, and an increased risk of behavioral, emotional, and intellectual difficulties. Life expectancy is normal. Hypogonadism results from abnormally low male sex hormone production and abnormally high female hormone levels.
Precocious puberty may result from germ-cell tumor production of male sex hormones in children with Klinefelter.
Screening and diagnosis:Cytogenetic analysis is necessary to diagnose Klinefelter's syndrome. Klinefelter is often discovered coincidentally during cytogenetic testing for cancer, infertility, or prenatal birth defects (amniocentesis). Doctors may notice clinical signs of Klinefelter's syndrome and request cytogenetic testing.
Treatment and therapy: Hormone replacement therapy is given to some patients to reduce symptoms and improve masculinization; however, testosterone therapy will increase the risk of prostate cancer. Patients may opt to have gynecomastia surgery to remove excess breast tissue. It is not necessary to treat Klinefelter's syndrome. Assisted reproductive technologies have been used to overcome sterility.
Prognosis, prevention, and outcomes: The long-term prognosis for Klinefelter's syndrome is good because, although there is no cure, the condition is not life-threatening. Surveillance for cancers that are more common in men with Klinefelter's syndrome should be instituted. Treatments that target symptoms should be performed if the patient wants the option.
Bibliography
Brinton, Louise A. “Breast Cancer Risk among Patients with Klinefelter Syndrome.” Acta Paediatrica (Oslo, Norway: 1992), vol. 100.6, 2011, pp. 814-8, doi:10.1111/j.1651-2227.2010.02131.x.
Gies, Inge et al. “Management of Klinefelter Syndrome during Transition.” European Journal of Endocrinology, vol. 171.2, 2014, pp. R67-77, doi:10.1530/EJE-14-0213.
“How Many People are Affected by or at Risk for Klinefelter Syndrome (KS)?” National Institute of Child Health and Human Development, 9 Jan. 2024, www.nichd.nih.gov/health/topics/klinefelter/conditioninfo/risk. Accessed 17 June 2024.
“Klinefelter Syndrome.” MedlinePlus, 10 July 2023, medlineplus.gov/genetics/condition/klinefelter-syndrome. Accessed 17 June 2024.
Parker, James N., and Philip M. Parker. Klinefelter’s Syndrome: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References. San Diego: ICON, 2004.
Wikström, Anne M, and Leo Dunkel. “Testicular Function in Klinefelter Syndrome.” Hormone Research, vol. 69.6, 2008, pp. 317-26, doi:10.1159/000117387.