Klinefelter Syndrome

(Klinefelter's Syndrome; XXY)

ByNina N. Powell-Hamilton, MD, Sidney Kimmel Medical College at Thomas Jefferson University
Reviewed/Revised Nov 2023

Klinefelter syndrome is a sex chromosome abnormality in which boys are born with two X chromosomes, instead of one, and one Y (XXY).

  • Klinefelter syndrome occurs when a boy has one extra X chromosome.

  • Boys may have learning disabilities, long arms and legs, small testes, and sometimes enlarged breasts.

  • The diagnosis is suspected at puberty when most of the symptoms develop.

Chromosomes are structures within cells that contain DNA and many genes. Genes are segments of deoxyribonucleic acid (DNA) and contain the code for a specific protein that functions in one or more types of cells in the body. Genes contain instructions that determine how the body is supposed to look and function. (See Genes and Chromosomes for a discussion about genetics.)

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. Most boys inherit the extra X chromosome from their mother.

Symptoms of Klinefelter Syndrome

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, for some boys, the breasts may enlarge somewhat (gynecomastia). Males with the syndrome are often 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.

Klinefelter Syndrome
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This photo shows enlarged breasts (gynecomastia) and small testes and penis in a male who has Klinefelter syndrome.
© Springer Science+Business Media

Diagnosis of Klinefelter Syndrome

  • Before birth, testing of the mother

  • After birth, blood test

Before birth, Klinefelter syndrome is usually only diagnosed incidentally when genetic testing 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. (See also Next-generation sequencing technologies.)

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 during an infertility assessment.

Treatment of Klinefelter Syndrome

  • For children, speech and language therapy

  • For adolescents, testosterone hormone replacement therapy for life

Boys with Klinefelter syndrome usually benefit from speech and language therapy and eventually can do well in school.

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.

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