Klinefelter syndrome is a condition in which one or more extra X chromosomes are present in a male. Boys with this condition appear normal at birth. They enter puberty normally, but by mid puberty have low levels of testosterone causing small testicles and the inability to make sperm. Affected males may also have learning disabilities and behavior problems such as shyness and immaturity and at an increased risk for certain other health problems.

Klinefelter syndrome is one of the most common chromosomal abnormalities. About 1 in every 500 to 800 males is born with this disorder; approximately 3000 affected boys are born each year in the United States. About 3% of the infertile male population have Klinefelter syndrome. The condition appears to affect all racial and ethnic groups equally.

Chromosomes are found in the cells in the body. Chromosomes contain genes, structures that tell the body how to grow and develop. Chromosomes are responsible for passing on hereditary traits from parents to child. Chromosomes also determine whether the child will be male or female. Normally, a person has a total of 46 chromosomes in each cell, two of which are responsible for determining that individual's sex. These two sex chromosomes are called X and Y. The combination of these two types of chromosomes determines the sex of a child. Females have two X chromosomes (the XX combination); males have one X and one Y chromosome (the XY combination).

In Klinefelter syndrome, a problem very early in development results in an abnormal number of chromosomes. About 60% of embryos with Klinefelter syndrome do not survive the fetal period. Most commonly, a male with Klinefelter syndrome will be born with 47 chromosomes in each cell, rather than the normal number of 46. The extra chromosome is an X chromosome. This means that rather than having the normal XY combination, the male has an XXY combination. Because people with Klinefelter syndrome have a Y chromosome, they are all male.

Approximately 1/3 of all males with Klinefelter syndrome have other chromosomal abnormalities involving an extra X chromosome. Mosaic Klinefelter syndrome occurs when some of the cells in the body have an extra X chromosome and the others have normal male chromosomes. These males can have the same or milder symptoms than non-mosaic Klinefelter syndrome. Males with more than one additional extra X chromosome, such as 48,XXXY, are usually more severely affected than males with 47,XXY.

Klinefelter syndrome is not considered an inherited condition. The risk of Klinefelter syndrome reoccurring in another pregnancy is not increased above the general population risk.

The symptoms of Klinefelter syndrome are variable and not every affected person will have all of the features of the condition. Males with Klinefelter syndrome appear normal at birth and have normal male genitalia. From childhood, males with Klinefelter syndrome are taller than average with long limbs. Approximately 20–50% have a mild intention tremor, an uncontrolled shaking. Many males with Klinefelter syndrome have poor upper body strength and can be clumsy. Klinefelter syndrome does not cause homosexuality. Approximately 1/3 of males with Klinefelter syndrome have gynecomastia or breast growth, some requiring breast reduction surgery.

Most boys enter puberty normally, though some can be delayed. The Leydig cells in the testicles usually produce testosterone. With Klinefelter syndrome, the Leydig cells fail to work properly causing the testosterone production to slow. By mid-puberty, testosterone production is decreased to approximately half of normal. This can lead to decreased facial and pubic hair growth. The decreased testosterone also causes an increase in two other hormones, follicle stimulating hormone (FSH) and luteinizing hormone (LH). Normally, FSH and LH help the immature sperm cells grown and develop. In Klinefelter syndrome, there are few or no sperm cells. The increased amount of FSH and LH cause hyalinization and fibrosis, the growth of excess fibrous tissue, in the seminiferous tubules, where the sperm are normally located. As a result, the testicles appear smaller and firmer than normal. With rare exception, men with Klinefelter syndrome are infertile because they can not make sperm.

While it was once believed that all boys with Klinefelter syndrome are mentally retarded, doctors now know that the disorder can exist without retardation. However, children with Klinefelter syndrome frequently have difficulty with language, including learning to speak, read, and write. Approximately 50% of males with Klinefelter syndrome are dyslexic.

Some people with Klinefelter syndrome have difficulty with social skills and tend to be more shy, anxious, or immature than their peers. They can also have poor judgment and do not handle stressful situations well. As a result, they often do not feel comfortable in large social gatherings. Some people with Klinefelter syndrome can also have anxiety, nervousness and/or depression.

The greater the number of X chromosomes present, the greater the disability; each extra X chromosome lowers the child's IQ by about 15 points. Boys with several extra X-chromosomes have distinctive facial features, more severe retardation, deformities of bony structures, and even more disordered development of male features.

Diagnosis of Klinefelter syndrome is made by examining chromosomes for evidence of more than one X chromosome present in a male. This can be done in pregnancy with prenatal testing such as a chorionic villus sampling or amniocentesis. Chorionic villus sampling is a procedure done early in pregnancy (approximately 10–12 weeks) to obtain a small sample of the placenta for testing. An amniocentesis is done further along in pregnancy (from approximately 16–18 weeks) to obtain a sample of fluid surrounding the baby for testing. Both procedures have a risk of miscarriage. Usually these procedures are done for a reason other than diagnosing Klinefelter syndrome. For example, a prenatal diagnostic procedure may be done on an older woman to determine if her baby has Down syndrome. If the diagnosis of Klinefelter syndrome is suspected in a young boy or adult male, chromosome testing can also be on a small blood or skin sample after birth.

Many men with Klinefelter syndrome go through life without being diagnosed. The two most common complaints leading to diagnosis of the condition are gynecomastia and infertility.

There is no treatment available as of the early 2000s to change a person's chromosomal makeup. Children with Klinefelter syndrome may benefit from speech therapy for speech problems or other educational interventions for learning disabilities. Testosterone injections started around the time of puberty may help to produce more normal development including more muscle mass, hair growth and increased sex drive. Testosterone supplementation will not increase testicular size, decrease breast growth or correct infertility. Psychiatric consultation may be helpful when the boy reaches adolescence.

Some doctors recommend mastectomy as a surgical treatment for gynecomastia, on the grounds that the enlarged breasts are often socially stressful for affected males and significantly increase their risk of breast cancer.

While many men with Klinefelter syndrome go on to live normal lives, nearly 100% of these men will be sterile (unable to produce a child). However, a few men with Klinefelter syndrome have been reported who have fathered a child through the use of assisted fertility services.

Males with Klinefelter syndrome have an increased risk of several systemic conditions, including epilepsy, osteoporosis, such autoimmune disorders as lupus and arthritis, diabetes, and breast and germ cell tumors. One Danish study reported in 2004 that men with Klinefelter's syndrome have a slightly shortened life span, dying about 2.1 years earlier than men without the syndrome.