Klinefelter syndrome is a condition that occurs in men as a result of an extra X chromosome. The most common symptom is infertility.
Humans have 46 chromosomes, which contain all of a person's genes and DNA. Two of these chromosomes, the sex chromosomes, determine a person?s gender. Both of the sex chromosomes in females are called X chromosomes. (This is written as XX.) Males have an X and a Y chromosome (written as XY). The two sex chromosomes help a person develop fertility and the sexual characteristics of their gender.
Most often, Klinefelter syndrome is the result of one extra X (written as XXY). Occasionally, variations of the XXY chromosome count may occur, the most common being the XY/XXY mosaic. In this variation, some of the cells in the male's body have an additional X chromosome, and the rest have the normal XY chromosome count. The percentage of cells containing the extra chromosome varies from case to case. In some instances, XY/XXY mosaics may have enough normally functioning cells in the testes to allow them to father children.
Klinefelter syndrome is found in about 1 out of every 500-1,000 newborn males. The additional sex chromosome results from a random error during the formation of the egg or sperm. About half of the time the error occurs in the formation of sperm, while the remainder are due to errors in egg development. Women who have pregnancies after age 35 have a slightly increased chance of having a boy with this syndrome.
Males who have Klinefelter syndrome may have the following symptoms: small, firm testes, a small penis, sparse pubic, armpit and facial hair, enlarged breasts (called gynecomastia), tall stature, and abnormal body proportions (long legs, short trunk).
School-age children may be diagnosed if they are referred to a doctor to evaluate learning disabilities. The diagnosis may also be considered in the adolescent male when puberty is not progressing as expected. Adult males may come to the doctor because of infertility.
Klinefelter syndrome is associated with an increased risk for breast cancer, a rare tumor called extragonadal germ cell tumor, lung disease, varicose veins and osteoporosis. Men who have Klinefelter syndrome also have an increased risk for autoimmune disorders such as lupus, rheumatoid arthritis and Sjogren's syndrome.
A chromosomal analysis (karyotype) is used to confirm the diagnosis. In this procedure, a small blood sample is drawn. White blood cells are then separated from the sample, mixed with tissue culture medium, incubated, and checked for chromosomal abnormalities, such as an extra X chromosome.
The chromosome analysis looks at a number of cells, usually at least 20, which allows for the diagnosis of genetic conditions in both the full and mosaic state. In some cases, low-level mosaicism may be missed. However, if mosaicism is suspected (based on hormone levels, sperm counts, or physical characteristics), additional cells can be analyzed from within the same blood draw.
Testosterone therapy is used to increase strength, promote muscular development, grow body hair, improve mood and self esteem, increase energy and improve concentration.
Most men who have Klinefelter syndrome are not able to father children. However, some men with an extra X chromosome have fathered healthy offspring, sometimes with the help of infertility specialists.
Most men who have Klinefelter syndrome can expect to have a normal and productive life. Early diagnosis, in conjunction with educational interventions, medical management, and strong social support will optimize each individual?s potential in adulthood.
NHGRI is not currently conducting clinical research for Klinefelter syndrome.
Last Updated: October 13, 2011