(Klinefelter's Syndrome; XXY)
Klinefelter syndrome is a sex chromosome abnormality in which boys are born with an extra X chromosome (XXY).
Chromosomes are structures within cells that contain DNA and many genes. A gene is a segment of deoxyribonucleic acid (DNA) and contains the code for a specific protein that functions in one or more types of cells in the body (see Genes and Chromosomes for a discussion about genetics). Genes contain instructions that determine how the body is supposed to function.
The sex chromosomes determine whether a fetus becomes male or female. A pair of X and Y chromosomes (XY) results in a male, and a pair of X and X chromosomes (XX) results in a female.
Klinefelter syndrome is the most common sex chromosome disorder and occurs in about 1 in every 500 live male births. Most boys inherit the extra X chromosome from their mother. Most boys with Klinefelter syndrome have normal or slightly decreased intelligence. Many have speech and reading disabilities and difficulties with planning. Most have problems with language skills. Lack of insight, poor judgment, and impaired ability to learn from previous mistakes often cause these children to get into trouble. Although their physical characteristics can vary greatly, most are tall with long arms and legs. They may also have wider hips but otherwise have a relatively normal appearance.
Puberty usually occurs at the normal time, but the testes remain small. At puberty, growth of facial hair is often sparse, and the breasts may enlarge somewhat (gynecomastia). Males with the syndrome are usually infertile, but sometimes the testes develop enough to produce sperm. Men with Klinefelter syndrome tend to develop diabetes mellitus, chronic lung disease, varicose veins, hypothyroidism, and breast cancer more often than other men.
Some affected boys have 3, 4, and even 5 X chromosomes along with the Y. As the number of X chromosomes increases, the severity of intellectual disability and physical abnormalities also increases. Each extra X is associated with a 15- to 16-point reduction in intelligence quotient (IQ), with language most affected, particularly expressive language skills.
Before birth, Klinefelter syndrome is usually only diagnosed incidentally when chromosome analysis is done for another reason. For example, amniocentesis or chorionic villus sampling may have been done to obtain cells from the fetus for chromosome analysis if the mother was 35 years or older when pregnant.
After birth, the syndrome is usually first suspected at puberty, when most of the symptoms develop. Analysis of the chromosomes using a blood test confirms the diagnosis of Klinefelter syndrome. However, many men are diagnosed only during an infertility assessment.
Boys with Klinefelter syndrome usually benefit from speech and language therapy and eventually can do well in school.
Males with Klinefelter syndrome benefit by taking supplemental testosterone for life beginning at puberty. The hormone improves bone density, making fractures less likely, and stimulates development of a more masculine appearance. Hormone replacement therapy may help lessen some behavior problems.
More recently, fertility preservation counseling has become an important part of the care of adolescents with Klinefelter syndrome. Obtaining and preserving sperm cells from males who produce them can give them the opportunity to father biological children.