A sex chromosome disorder characterized by low levels of male hormones, sterility, breast enlargement, and small testes. Men who have Klinefelter syndrome also are at greater risk of developing testicular cancer.

Normal boys have an X chromosome and a Y chromosome (XY); in Klinefelter syndrome, the boy has one Y (male) and two X (female) chromosomes. In Klinefelter the affected boy has a genetic signature of XXY with a total of 47 chromosomes within each cell, instead of the normal 48.

Klinefelter syndrome occurs in about one of every 500 live births; often it is not diagnosed until puberty.

History

In 1942 Dr. Harry Klinefelter and his coworkers at the Massachusetts General Hospital in Boston published a report about nine men who had enlarged breasts, sparse facial and body hair, small testes, and inability to produce sperm. It was not until the late 1950s that researchers discovered that these men had Klinefelter’s syndrome and an extra sex chromosome. In the early 1970s, researchers around the world sought to identify boys who had the extra chromosome by screening large numbers of newborn babies. One of the largest of these studies, sponsored by the National Institute of Child Health and Human Development (NICHD), checked the chromosomes of more than 40,000 infants. On the basis of these studies, the XXY chromosome arrangement appears to be one of the most common genetic abnormalities known. Although the syndrome’s cause (an extra sex chromosome) is common, the syndrome itself — the set of symptoms and characteristics that may result from having the extra chromosome — is not common. In fact, many men live out their lives without ever even suspecting that they have an additional chromosome.

Cause

No one knows what puts a couple at risk for conceiving an XXY child. Advanced maternal age only slightly increases the risk of the XXY chromosome count. Furthermore, recent studies conducted by Case Western Reserve University researchers show that half the time, the extra chromosome is passed on by the father.

In some cases, the X chromosomes — or the X chromosome and Y chromosome — do not pair and do not exchange genetic material. Occasionally, this causes them to move independently to the same cell, producing either an egg that has two Xs or a sperm that has both an X and a Y chromosome. When a sperm that has both an X and a Y chromosome fertilizes an egg that has a single X chromosome, or a normal Y-bearing sperm fertilizes an egg that has two X chromosomes, an XXY male is conceived.

Because these boys often do not appear to be different from anyone else, many XXY males probably never learn of their extra chromosome. They are usually diagnosed before or shortly after birth, during early childhood or adolescence, or as a result of infertility testing in adulthood. In recent years, many XXY males have been diagnosed before birth, through amniocentesis or chorionic villus sampling (CVS).

Cancer Risk

XXY males who have enlarged breasts have the same risk of breast cancer as women — about 50 times the risk of a normal male. For this reason, XXY adolescents and men need to practice regular breast self-examination. XXY males may also wish to consult their physicians about the need for more thorough breast examinations by medical professionals.

Symptoms

This syndrome causes testicular failure that is due to hardening of the tubules within the testes. In some individuals, more complicated genetic patterns (called mosaicism) such as XXYY, XXXY, or XXXXY have been found. Skeletal abnormalities are more common among men who have multiple X chromosomes.

Patients who have chromosomal mosaics (XXY/XY) have a less severe form of Klinefelter’s syndrome and may be fertile, since a normal (XY) group of sperm-producing seminiferous tubules may exist within the testes.

In adolescent boys, Klinefelter syndrome may produce small firm testes, overdevelopment of the male breasts, slowed growth of facial hair, and incomplete masculine body build. Most young men who have Klinefelter syndrome are tall (the average height is about six feet), but they may not be coordinated or athletic. Psychological, social and learning problems are common in this group, as is mental retardation. Other associated conditions include glucose intolerance (inability to metabolize sugar) and varicose veins in the legs.

High levels of gonadotropins are usually found in the blood, and there is an imbalance in blood levels of estradiol (a form of the female sex hormone estrogen) and androgbn (male sex hormone).

Although most adult men who have Klinefelter syndrome have normal sexual function with adequate erection and ejaculation, some maybe impotent or have a low sex drive, and they may exhibit incomplete development of the scrotum or penis. Sperm are not produced.

Treatment

Counseling can help overcome any related depression or other psychological problems. Testosterone therapy may help boys who have Klinefelter syndrome, especially if their hormonal levels are low. Specialists generally recommend hormone therapy to ensure sexual development, including growth of pubic and facial hair, increased size of the penis and scrotum, deepening of the voice, and increased muscular size and strength. Therapy includes use of synthetic testosterone. Treatment, however, does not repair the sperm production problems nor protect against the development of testicular cancer.

Klinefelter Syndrome and Associates

A nonprofit organization founded in 1989 by Melissa Aylstock, mother of a son who had the condition. The organization distributes a newsletter three times a year to more than 1,400 patients, families, physicians, and support organizations. The association also participates actively in research and educational projects about Klinefelter’s syndrome and other male sex chromosome variations.

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