Klinefelter syndrome

Klinefelter syndrome is a chromosomal condition in boys and men that can affect physical and intellectual development. Its signs and symptoms vary among affected individuals. In some cases, the features of the condition are so mild that the condition is not diagnosed until puberty or adulthood, and researchers believe that some affected men and boys are never diagnosed.

Boys and men with Klinefelter syndrome typically have small testes that produce a reduced amount of testosterone. Testosterone is the hormone that directs male sexual development before birth and during puberty. Without treatment, the shortage of testosterone can lead to delayed or incomplete puberty, breast enlargement (gynecomastia), and a reduced amount of facial and body hair. As a result of the small testes and decreased hormone production, affected males are unable to father biological children (infertile) without assisted reproductive technologies. Some affected individuals also have differences in their genitalia, including undescended testes, the opening of the urethra on the underside of the penis (hypospadias), or an unusually small penis (micropenis).

Other physical changes associated with Klinefelter syndrome are usually subtle. Older children and adults with the condition tend to be somewhat taller than their peers. Other differences can include abnormal fusion of certain bones in the forearm (radioulnar synostosis), curved pinky fingers (fifth finger clinodactyly), and flat feet (pes planus).

Children with Klinefelter syndrome may have weak muscle tone (hypotonia) and problems with coordination that delay the development of motor skills, such as sitting, standing, and walking. Affected boys often have learning disabilities, problems with reading, and mild delays in speech and language development. Boys and men with Klinefelter syndrome tend to have better receptive language skills (the ability to understand speech) than expressive language skills (vocabulary and the production of speech) and may have difficulty communicating and expressing themselves. They tend to have anxiety, impaired social skills, a short attention span, and limited problem-solving skills (executive functioning)

Compared with unaffected men, adults with Klinefelter syndrome have an increased risk of developing type 2 diabetes, blood clots, involuntary trembling (tremors), breast cancer (if gynecomastia develops), thinning and weakening of the bones (osteoporosis), and autoimmune disorders such as systemic lupus erythematosus and rheumatoid arthritis. (Autoimmune disorders are a large group of conditions that occur when the immune system attacks the body's own tissues and organs.)

Klinefelter syndrome affects 1 in 500 to 1,000 newborn boys. It is among the most common sex chromosome disorders, which are conditions caused by changes in the number of sex chromosomes (the X chromosome and the Y chromosome).

Klinefelter syndrome is a sex chromosome disorder in boys and men that results from the presence of an extra X chromosome in cells. People typically have 46 chromosomes in each cell, two of which are the sex chromosomes. Females have two X chromosomes (46,XX), and males have one X and one Y chromosome (46,XY). Most often, boys and men with Klinefelter syndrome have the usual X and Y chromosomes, plus one extra X chromosome, for a total of 47 chromosomes (47,XXY).

Boys and men with Klinefelter syndrome have an extra copy of multiple genes on the X chromosome. The activity of these extra genes affects many aspects of development, including sexual development before birth and at puberty. Researchers are working to determine which genes contribute to the specific developmental and physical differences that can occur with Klinefelter syndrome.

Some people with features of Klinefelter syndrome have an extra X chromosome in only some of their cells; other cells have one X and one Y chromosome. In these individuals, the condition is described as mosaic Klinefelter syndrome (46,XY/47,XXY). Boys and men with mosaic Klinefelter syndrome may have milder signs and symptoms than those with the extra X chromosome in all of their cells, depending on what proportion of cells have the additional chromosome.

Several conditions resulting from the presence of more than one extra sex chromosome in each cell are sometimes described as variants of Klinefelter syndrome. These conditions include 48,XXXY syndrome, 48,XXYY syndrome, and 49,XXXXY syndrome. Like Klinefelter syndrome, these conditions affect male sexual development and can be associated with learning disabilities and problems with speech and language development. However, the features of these disorders tend to be more severe than those of Klinefelter syndrome and affect more parts of the body. As doctors and researchers have learned more about the differences between these sex chromosome disorders, they have started to consider them as separate conditions.

Klinefelter syndrome is not inherited; the addition of an extra X chromosome occurs during the formation of reproductive cells (eggs or sperm) in one of an affected person's parents. During cell division, an error called nondisjunction prevents X chromosomes from being distributed normally among reproductive cells as they form. Typically, as cells divide, each egg cell gets a single X chromosome, and each sperm cell gets either an X chromosome or a Y chromosome. However, because of nondisjunction, an egg cell or a sperm cell can also end up with an extra copy of the X chromosome.

If an egg cell with an extra X chromosome (XX) is fertilized by a sperm cell with one Y chromosome, the resulting child will have Klinefelter syndrome. Similarly, if a sperm cell with both an X chromosome and a Y chromosome (XY) fertilizes an egg cell with a single X chromosome, the resulting child will have Klinefelter syndrome.

Mosaic Klinefelter syndrome (46,XY/47,XXY) is also not inherited. It occurs as a random error during cell division early in fetal development. As a result, some of the body's cells have the usual one X chromosome and one Y chromosome (46,XY), and other cells have an extra copy of the X chromosome (47,XXY).

  • 47,XXY syndrome
  • Klinefelter syndrome (KS)
  • Klinefelter's syndrome
  • XXY syndrome
  • XXY trisomy