Klinefelter Syndrome

What is Klinefelter syndrome?

Klinefelter syndrome is a chromosomal anomaly that affects males. It occurs when a boy is born with an extra X chromosome.

Symptoms can be subtle and many men do not realize that they are affected. Boys born with the condition usually come to medical attention during puberty because they fail to complete puberty normally, produce less testosterone than their peers or develop breast enlargement. About 10 percent of cases are diagnosed prenatally during routine prenatal testing such as amniocentesis.

Klinefelter syndrome affects 1 in 500-1,000 newborn males, making it is one of the most common chromosomal disorders.

Signs and symptoms

Signs and symptoms of Klinefelter syndrome vary and may include:

  • Small testes that produce less testosterone
  • Delayed or incomplete puberty
  • Reduced facial or body hair
  • Breast enlargement (gynecomastia)
  • Learning disabilities
  • Delayed speech and language development
  • Reduced fertility or infertility

Causes

Klinefelter syndrome is a genetic condition but it is not inherited. It is caused by a random event during cell division early in fetal development.

The syndrome is linked to an abnormal number of sex chromosomes. Typically, males have an X and a Y chromosome, and females have two X chromosomes.

In Klinefelter syndrome, there are two X chromosomes and a Y chromosome (XXY). In rare cases, additional X chromosomes (XXXY or XXXXY) may also be linked to Klinefelter syndrome.

Diagnosis and testing

The condition is confirmed genetically by the demonstration of one or more extra X chromosomes. Elevations of puberty hormone levels such as LH (lutenizing hormone) and FSH (follicle-stimulating hormone) are frequently seen. Testosterone levels vary but are usually in the low normal range.

Treatment

While Klinefelter syndrome cannot be cured, some of its symptoms can be improved by testosterone replacement therapy, which restores testosterone levels to normal range.

In some cases, surgery may be necessary to correct certain symptoms of Klinefelter syndrome, such as abnormal breast tissue.

Some boys function quite normally, but learning and psychosocial difficulties may be seen in a significant number. These boys benefit from evaluation by a neurodevelopmental pediatrician, early intervention or behavior therapy.

Fertility can be restored with advanced reproductive techniques, such as surgically removed sperm material and IVF. 

In the Adrenal and Puberty Center at CHOP, our team will work with your family to develop an individualized plan to treat and monitor your child’s condition. In addition to our core team of endocrinology and genetics, your child may benefit from evaluation by neurodevelopmental pediatrics, family counseling and reproductive specialists that are available through our center.

Follow-up care

Boys with Klinefelter syndrome should follow up with the endocrinologist to monitor progression in puberty, hormone levels and adjust medication as needed.

Depending on your child’s condition, long-term care may be needed. At the Adrenal and Puberty Center, we bring endocrinologists, geneticists, urologists, counselors and nurses together to deliver the best-coordinated care for your child. In addition, your child has access to our team of neurodevelopmental pediatrics and reproductive specialists.

Outlook

With proper diagnosis and treatment, some of the symptoms of Klinefelter syndrome, such as low testosterone levels, can be resolved or well-controlled. Learning impairments can be overcome with early intervention. Fertility is sometimes possible with advanced reproductive assistance.

As children with Klinefelter syndrome become adults, they are often taller than their peers and have an increased chance of developing breast cancer and systemic lupus erythematosus, a chronic inflammatory disease.