Klinefelter syndrome
Definition
Klinefelter syndrome, also called 47,XXY, is a genetic condition that occurs in males when they have an extra X chromosome. This can cause problems with development and fertility. Some men have no symptoms and never know they have it.
Alternative Names
47 XXY syndrome; XXY syndrome; XXY trisomy; 47,XXY/46,XY; 47,XXY/46,XY mosaicism; Poly-X Klinefelter syndrome
Causes
Most people have 46 chromosomes. Chromosomes contain all of your genes and DNA, the building blocks of the body. The 2 sex chromosomes (X and Y) determine the genetic sex of a child. The genetic sex of a child is determined at conception. The mother's egg cell contains an X chromosome, while the father's sperm cell contains either an X or a Y chromosome.
Normally, an infant inherits 1 pair of sex chromosomes, 1 X from the mother and 1 X or 1 Y from the father. A baby who inherits the X chromosome from the father is a genetic female and has 2 X chromosomes. A baby who inherits the Y chromosome from the father is a genetic male and has 1 X and 1 Y chromosome.
Klinefelter syndrome results when a male child is born with at least 1 extra X chromosome. They have 47 chromosomes instead of 46. This is written as 47, XXY.
Klinefelter syndrome occurs as a random event. There is no exact cause, and the condition is not inherited.
Klinefelter syndrome occurs in about 1 out of 500 to 1,000 male infants. Women who get pregnant after age 35 are slightly more likely to have a male child with this syndrome than younger women.
Symptoms
Symptoms vary widely, with some males having few or only mild signs. Some may never know they have the condition or only discover it as adults when they have fertility problems. Others experience delayed growth and development in childhood.
Symptoms may include any of the following:
- Urethra on the underside of the penis (hypospadias)
- Testicles that have not moved into the scrotum
- Being slow to sit up, walk, crawl, and speak
- Delayed puberty
- Small, firm testicles
- Language learning disorders, including dyslexia, which affects reading
- Abnormal body proportions (long legs, short trunk, shoulder equal to hip size)
- Enlarged breasts (gynecomastia)
- Less than normal amount of pubic, armpit, and facial hair
- Tall height
- Small penis size
- Infertility
- Sexual problems
- Social, emotional, or behavioral problems
- Mental health conditions such as depression or anxiety
Exams and Tests
Klinefelter syndrome may first be diagnosed when a man comes to their health care provider because of infertility. Or it may be diagnosed if a male child does not develop normally during puberty. The following tests may be performed:
- Karyotyping (checks the chromosomes)
- Semen analysis
Blood tests will be done to check hormone levels, including:
- Estradiol, a type of estrogen
- Follicle stimulating hormone
- Luteinizing hormone
- Testosterone
Some cases of Klinefelter syndrome are discovered during prenatal tests for other genetic conditions. Follow-up testing of the baby after birth is needed to confirm the diagnosis.
Treatment
While there is no cure, treatment can help improve symptoms. Depending on symptoms, the health care team may include a number of specialists:
- Endocrinologist
- Speech and language therapist
- Physical therapist
- Mental health counselor
- Infertility specialist
Testosterone therapy may be prescribed. This can help:
- Grow body hair
- Deepen the voice
- Strengthen bones
- Improve muscle strength and bulk
- Improve concentration
- Improve mood and self esteem
- Increase energy and sex drive
Males who have excess breast tissue may decide to have it surgically removed.
If you have Klinefelter syndrome and wish to have children, it's a good idea to work with an infertility specialist. Many men with this syndrome cannot produce enough sperm to have children. However, some men may be helped with newer reproductive technologies.
Support Groups
More information and support for people with Klinefelter syndrome and their families can be found at:
- Association for X and Y Chromosome Variations -- genetic.org
- Living with XXY - livingwithxxy.org/
- US National Library of Medicine, MedlinePlus -- medlineplus.gov/klinefeltersyndrome.html
Possible Complications
Men with Klinefelter syndrome have an increased risk of a number of other health conditions:
- Attention deficient hyperactivity disorder (ADHD)
- Autism spectrum disorder
- Autoimmune disorders, such as lupus, rheumatoid arthritis, and Sjögren syndrome
- Breast cancer in men
- Depression
- Extragonadal germ cell tumor (rare)
- Lung disease
- Osteoporosis
- Varicose veins
- Metabolic syndrome
- Oral health problems
- Obesity
When to Contact a Medical Professional
Contact your provider if your child has any signs or symptoms of Klinefelter syndrome. Also contact your provider if your child does not develop male sexual characteristics during puberty. This includes facial hair growth and a deeper voice.
Adult males with this condition should see their provider for regular health exams to check for and manage possible health problems.
References
Bacino CA, Lee B. Cytogenetics. In: Kliegman RM, St Geme JW, Blum NJ, Shah SS, Tasker RC, Wilson KM, eds. Nelson Textbook of Pediatrics. 21st ed. Philadelphia, PA: Elsevier; 2020:chap 98
Escobar O, Gurtunca N, Viswanathan P, Witchel SF. Pediatric endocrinology. In: Zitelli BJ, McIntire SC, Nowalk AJ, Garrison J, eds. Zitelli and Davis' Atlas of Pediatric Physical Diagnosis. 8th ed. Philadelphia, PA: Elsevier; 2023:chap 9.
Marcdante KJ, Kliegman RM, Schuh AM. Chromosomal disorders. In: Marcdante KJ, Kliegman RM, Schuh AM, eds. Nelson Essentials of Pediatrics. 9th ed. Philadelphia, PA: Elsevier; 2023:chap 49.
Matsumoto AM, Anawalt BD. Testicular disorders. In: Melmed S, Auchus RJ, Goldfine AB, Koenig RJ, Rosen CJ, eds. Williams Textbook of Endocrinology. 14th ed. Philadelphia, PA: Elsevier; 2020:chap 19.
Yu RN, Diamond DA. Disorders of sexual development: etiology, evaluation, and medical management. In: Partin AW, Dmochowski RR, Kavoussi LR, Peters CA, eds. Campbell-Walsh-Wein Urology. 12th ed. Philadelphia, PA: Elsevier; 2021:chap 48.
Reviewed By: Anna C. Edens Hurst, MD, MS, Associate Professor in Medical Genetics, The University of Alabama at Birmingham, Birmingham, AL. Review provided by VeriMed Healthcare Network. Also reviewed by David C. Dugdale, MD, Medical Director, Brenda Conaway, Editorial Director, and the A.D.A.M. Editorial team.
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