Klinefelter Syndrome

Klinefelter syndrome is a chromosomal condition that affects male sexual development. Most males with Klinefelter syndrome have one extra copy of the X chromosome in each cell. Because their testicles do not develop normally, affected males may have low levels of the hormone testosterone beginning during puberty. A lack of this hormone can lead to breast development (gynecomastia), reduced facial and body hair, and an inability to father children (infertility). Compared with other men, adult males with Klinefelter syndrome have an increased risk of developing breast cancer and a chronic inflammatory disease called systemic lupus erythematosus. Their chance of developing these disorders is similar to that of normal adult females.

Other Names

• Klinefelter's Syndrome
• 47,XXY
• XXY syndrome
• XXY trisomy

Signs and Symptoms

Not all males with the condition have the same symptoms or to the same degree. Symptoms depend on how many XXY cells a man has, how much testosterone is in his body, and his age when the condition is diagnosed. The XXY condition can affect three main areas of development:

Physical development

As babies, many XXY males have weak muscles and reduced strength. They may sit up, crawl, and walk later than other infants. After about age four, XXY males tend to be taller and may have less muscle control and coordination than other boys their age.

As XXY males enter puberty, they often don’t make as much testosterone as other boys. This can lead to a taller, less muscular body, less facial and body hair, and broader hips than other boys. As teens, XXY males may have larger breasts, weaker bones, and a lower energy level than other boys.

By adulthood, XXY males look similar to males without the condition, although they are often taller. They are also more likely than other men to have certain health problems, such as autoimmune disorders, breast cancer, vein diseases, osteoporosis, and tooth decay.

XXY males can have normal sex lives, but they usually make little or no sperm. Between 95 percent and 99 percent of XXY males are [/health/topics/infertility_fertility.cfm infertile] because their bodies don’t make a lot of sperm.

Language development

As boys, between 25 percent and 85 percent of XXY males have some kind of language problem, such as learning to talk late, trouble using language to express thoughts and needs, problems reading, and trouble processing what they hear.

As adults, XXY males may have a harder time doing work that involves reading and writing, but most hold jobs and have successful careers.

Social development

As babies, XXY males tend to be quiet and undemanding. As they get older, they are usually quieter, less self-confident, less active, and more helpful and obedient than other boys.

As teens, XXY males tend to be quiet and shy. They may struggle in school and sports, meaning they may have more trouble “fitting in” with other kids.

However, as adults, XXY males live lives similar to men without the condition; they have friends, families, and normal social relationships. ^[1]

Variants of Klinefelter syndrome, which involve more than one extra X chromosome or extra copies of both the X and Y chromosomes in each cell, tend to have more severe signs and symptoms. These disorders affect male sexual development and are associated with decreased IQ, distinctive facial features, skeletal abnormalities, poor coordination, and severe problems with speech.

Causes

People typically have two sex chromosomes in each cell; females have two X chromosomes, and males have one X chromosome and one Y chromosome. Klinefelter syndrome is caused by the presence of one or more extra copies of the X chromosome in a male's cells. Extra copies of genes on the X chromosome interfere with male sexual development, preventing the testicles from functioning normally and reducing the levels of testosterone.

Most often, Klinefelter syndrome is caused by a single extra copy of the X chromosome, for a total of 47 chromosomes per cell. Males normally have one X chromosome and one Y chromosome in each cell (46,XY), but males with Klinefelter syndrome have two X chromosomes and one Y chromosome (47,XXY). Some males with Klinefelter syndrome have the extra X chromosome in only some of their cells; these cases are called mosaic 46,XY/47,XXY.

Treatment

The XXY chromosome pattern can not be changed. But, there are a variety of ways to treat the symptoms of the XXY condition.

Medications

Testosterone replacement therapy (TRT) can greatly help XXY males get their testosterone levels into normal range. Having a more normal testosterone level can help develop bigger muscles, deepen the voice, and grow facial and body hair. TRT often starts when a boy reaches puberty. Some XXY males can also benefit from fertility treatment to help them father children.

Educational treatments

As children, many XXY males qualify for special services to help them in school. Teachers can also help by using certain methods in the classroom, such as breaking bigger tasks into small steps.

Therapies

A variety of therapists, such as physical, speech, occupational, behavioral, mental health, and family therapists, can often help reduce or eliminate some of the symptoms of the XXY condition, such as poor muscle tone, speech or language problems, or low self-confidence. One of the most important factors for all types of treatment is starting it as early in life as possible. ^[2]

Chances of Developing Klinefelter Syndrome

Klinefelter syndrome affects 1 in 500 to 1,000 males. Variants of Klinefelter syndrome are much rarer, occurring in 1 in 50,000 or fewer male births. Females are not affected by Klinefelter syndrome.

Genetics

Klinefelter syndrome is related to chromosomes X and Y.

Heredity

This condition is not inherited, but usually occurs as a random event during the formation of reproductive cells (eggs and sperm). An error in cell division called nondisjunction can result in reproductive cells with an abnormal number of chromosomes. For example, an egg or sperm cell may gain one or more extra copies of the X chromosome as a result of nondisjunction. If one of these atypical reproductive cells contributes to the genetic makeup of a child, the child will have one or several extra X chromosomes in each of the body's cells.

Mosaic 46,XY/47,XXY occurs as a random error during cell division early in fetal development. As a result of this error, some cells have one X chromosome and one Y chromosome (46,XY), and other cells have an extra copy of the X chromosome (47,XXY).

Related Problems

Variants of Klinefelter syndrome are caused by several extra copies of the X chromosome or extra copies of both the X and Y chromosomes in all of the body's cells. The signs and symptoms of these conditions typically become more severe as the number of X chromosomes increases.

Other Resources

• MedlinePlus Encyclopedia: Klinefelter syndrome]
• MedlinePlus Encyclopedia: Testicular Failure]
• Educational resources and
• Patient support.
• MedlinePlus - Health information (3 links)
• Additional NIH Resources - National Institutes of HealthNational Institute of Child Health and Human Development]
• Educational resources - Information pages (7 links)
• Patient support - For patients and families (5 links)
• Genetic Tools] - Teaching cases
• ClinicalTrials.gov] - Linking patients to medical research
• PubMed] - Recent literature

References

1. ↑ Institute of Child Health and Human Development, NIH
2. ↑ Institute of Child Health and Human Development, NIH