What is Klinefelter syndrome?

Klinefelter syndrome is a chromosomal condition that affects 1 in 500 to 1,000 newborn males. People typically have two sex chromosomes in each cell: females have two X chromosomes (XX), while males have one X chromosome and one Y chromosome (XY). In most Klinefelter syndrome individuals, there is one extra copy of the X chromosome in each cell (XXY).

Usually, the chromosomal abnormality occurs at random during the formation of reproductive cells (eggs and sperm) in one of the affected child’s parents. Extra copies of genes on the X chromosome interfere with typical male sexual development, causing smaller but firm testicles (hypogonadism) and reduced testosterone production. This testosterone deficiency can lead to the following:

• Delayed or incomplete puberty
• Abnormally large breasts (gynecomastia)
• Sparse facial and body hair
• Infertility.

Besides hypogonadism, some affected individuals also have genital differences including:

• Undescended testes (cryptorchidism)
• Opening of the urethra on the underside of the penis (hypospadias)
• Shorter than normal penis length (micropenis).

Because the clinical features of Klinefelter syndrome are often subtle, the diagnosis is often not apparent until much later in life when a couple is undergoing an evaluation by an infertility specialist. Klinefelter syndrome is one of the most common causes of genetically determined infertility. While 80 percent of patients with Klinefelter syndrome have a XXY sex chromosome makeup in all of their cells, up to 20 percent of individuals are called “mosaic” because some cells have the usual male XY and others have XXY. Some even have more than one extra X chromosome (i.e., XXXY or XXXXY).

Children and adolescents with Klinefelter syndrome may suffer from learning disabilities (i.e. attention deficit hyperactivity disorder) as well as delayed speech and language development. They tend to be quiet, sensitive, and unassertive, but personality characteristics vary among affected individuals. Older children and adults with Klinefelter syndrome tend to be greater than average height. Breast cancer, weaker bones, and a chronic inflammatory disease called systemic lupus erythematosis are more common in men with Klinefelter syndrome.

Testosterone supplementation can help an individual with Klinefelter syndrome grow body hair, improve concentration, improve mood and self-esteem, increase energy and sex drive, and increase strength.

Reviewed by Dr. Sara Connolly, February 2019