Klinefelter's syndrome is a genetic condition that only affects males. Affected males have an extra X chromosome.
Males with Klinefelter's syndrome have small testes which do not produce enough of the male hormone testosterone before birth and during puberty. This lack of testosterone means that during puberty, the normal male sexual characteristics do not develop fully. There is reduced facial and pubic hair, and some breast tissue often develops. The lack of testosterone is also responsible for other symptoms, including infertility.
Treatment includes testosterone replacement. This can help improve some of the symptoms but does not have an effect on fertility. The majority of men with KS lead an independent life, forming relationships and getting a normal job. They also have a normal lifespan.
What is Klinefelter's syndrome?
In general, each cell in your body contains 46 chromosomes arranged in 23 pairs. One chromosome from each pair is inherited from your mother and the other is inherited from your father. One of these chromosome pairs is known as the sex chromosomes because this pair of chromosomes determines our sex.
Females have two of the same kind of sex chromosome (XX). Males have two different sex chromosomes (XY). The Y chromosome contains the male determining genes. So a female normally has 46, XX chromosomes and a male normally has 46, XY.
Klinefelter's syndrome (KS) is when males have an extra X chromosome. It is a genetic problem that only affects boys and men. It is a sex chromosome trisomy. Instead of being 46, XY, men or boys with KS are usually 47, XXY.
Dr Harry F. Klinefelter first described this syndrome in the USA in 1942. The condition affects sexual development. Males with KS have small testes which do not produce enough of the male hormone testosterone before birth and during puberty. This lack of testosterone means that during puberty, the normal male sexual characteristics do not develop fully. There is reduced facial and pubic hair, and some breast tissue may develop. The lack of testosterone is also responsible for some of the other symptoms (see below), including infertility.
In most cases, KS develops because there is an extra copy of the X chromosome in each of a male's cells (47, XXY). Because there are extra X chromosome genes, this interferes with male sexual development. The testes don't work normally and they produce lower levels of testosterone.
However, some males with KS only have the extra X chromosome in some of their cells. This is known as mosaic KS. If you have mosaic KS, you may be more mildly affected, depending on how many cells have an extra X chromosome. About 1 in 10 males with KS have mosaic KS. They are 46, XY; 47, XXY.
Rarely, males with KS can have several extra copies of the X chromosome or extra copies of both the X and Y chromosomes in all their body's cells. For example, they can be 48,XXYY, 48,XXXY, 49,XXXYY, and 49,XXXXY. These variants are rare, but if one does happen, males tend to have more severe symptoms.
What causes Klinefelter's syndrome?
KS is a genetic condition but it is not 'inherited' from your parents. It usually happens randomly during meiosis - cell division that produces egg and sperm cells (reproductive cells). Because of an error in cell division called nondisjunction, an egg or a sperm cell can have an extra copy of an X chromosome. This means that when it meets a 'normal' egg or sperm at conception, the embryo produced (which will go on to develop into the baby) will have one extra copy of the X chromosome in each of their body's cells. This is known as a sex chromosome trisomy (there are three sex chromosomes in the body's cells instead of two).
Mosaic KS also occurs randomly and is not 'inherited'. During early development in the womb, there is a problem with cell division. This means that some of the body's cells have one X chromosome and one Y chromosome (46, XY), and other cells have an extra copy of the X chromosome (47, XXY).
It is thought that mothers or fathers who are at an older age may be more likely to have a child with KS.
How common is Klinefelter's syndrome?
Between 1 in 500 and 1 in 1,000 boys are born with KS.
What are the symptoms of Klinefelter's syndrome?
KS is usually not noticed until you go through puberty. Puberty may be late or incomplete if you have KS. Sometimes the condition may only be diagnosed if you are investigated for infertility as an adult.
The typical features of KS in an adult are:
- Small testes.
- Decreased facial hair compared to a usual male.
- Gynaecomastia (some breast tissue development).
- Decreased pubic hair compared to a usual male.
- A tall, thin body with disproportionately long arms and legs.
- Obesity - this may cause a thicker waistline but it is often partially disguised by wider than normal hips.
Children and adolescents with KS may also have:
- A delay in the age of first walking.
- Dyspraxia (which causes co-ordination problems).
- Speech and language delay or difficulties.
- Attention problems.
- Mild learning disabilities.
- Dyslexia or reading problems.
- Behavioural problems - boys tend to be shy and have low self-confidence; they may appear to be immature when compared to their peers.
In adulthood, in addition to the main typical features:
- You may also have problems getting an erection and have a low libido (sex drive).
- Anxiety and depression may be a problem.
- 'Thin bones' (osteoporosis) may develop in young or middle age rather than the usual older age for this condition.
- You may also be less muscular than other men.
- Most men who are 47, XXY have normal intelligence. However, your intelligence may be affected if you have a higher number of X chromosomes.
- Almost all men who are 47, XXY will be infertile.
How is Klinefelter's syndrome diagnosed?
KS is often diagnosed when a man is being investigated for infertility. The diagnosis can be confirmed by a test called a karyotype. A blood sample is taken from the man and the chromosomes are studied. This test can show the extra X chromosome.
Sometimes KS is diagnosed in an unborn baby boy during antenatal screening carried out for another reason. If, for example, screening tests have shown an increased risk of Down's syndrome, the mother may go on to have a further test called an amniocentesis. This is where a sample is taken from the amniotic fluid around the baby in the womb (uterus). A karyotype test can then be done in the sample and can show if the baby has KS.
KS may also be diagnosed at the time of puberty. Puberty may be delayed or noticed as abnormal. A doctor may notice signs of KS when they examine you; for example, if your testes are small, or if you have breast tissue development or reduced pubic hair for your age. Your doctor may then suggest a karyotype blood test.
Other blood tests may also be done if your doctor suspects that you may have KS. These include hormone blood tests. For example, if you have KS, towards the end of puberty and in adulthood your levels of testosterone in your blood will be low.
What is the treatment for Klinefelter's syndrome?
If you have KS, you will usually be referred to a hormone specialist (an endocrinologist).
The main treatment for KS is with testosterone to boost the low levels. Ideally, testosterone replacement should begin at puberty and is needed lifelong. Testosterone can help to:
- Increase your strength and build a more muscular body type.
- Increase facial and pubic hair growth.
- Increase your libido (sex drive).
- Enlarge your testes.
- Improve your mood and self-esteem.
- Protect against 'thin bones' (osteoporosis).
However, testosterone treatment does not have any affect on your fertility. It also has little effect on breast tissue development (gynaecomastia).
Treatment for gynaecomastia
Gynaecomastia can be a troubling problem for males with KS. Sometimes men choose to have surgery to remove the breast tissue.
If you have KS and you are considering having children, you will need to see an infertility specialist. There have been great developments in the treatment of infertility over recent years and there have been cases of men with KS fathering children. Also, men with KS mosaicism (46,XY/47,XXY) can be fertile.
Investigation will show if you have any viable sperm in your testes. If this is the case, the sperm may be able to be extracted from your testes and then used for in vitro fertilisation (IVF) or intra-cytoplasmic sperm injection (ICSI). ICSI involves an individual sperm being injected directly into an egg. The egg containing the sperm is then placed in the womb (uterus) in the same way as with IVF. See separate leaflet called Infertility - a Summary of Treatments for more detail.
However, you should first see a genetic counsellor. This is because the exact risk of someone with KS having a child with KS or another chromosomal problem is unknown, but it appears to be low.
Other treatments for KS may include, for example, speech and language therapy and behavioural therapy in children (if required). Physiotherapy and occupational therapy are also sometimes needed.
What are the complications of Klinefelter's syndrome?
Males with KS may have an increased risk of certain conditions including:
- Cardiovascular disease - this is due to increased cholesterol levels which may occur and the risk can be reduced with testosterone treatment.
- 'Thin bones' (osteoporosis) - low levels of testosterone increase the risk of developing osteoporosis. If you have KS you should have regular bone density screening tests.
- Breast cancer - the risk of developing breast cancer is about 20 times higher than in otherwise healthy men. If you have KS, you should regularly examine your breast area and see your doctor if you notice any lumps or have any concerns.
- Thromboembolism - men with KS have an increased risk of deep vein thrombosis and blood clots in blood vessels (pulmonary embolism).
- Autoimmune diseases - these include systemic lupus erythematosus, rheumatoid arthritis and Sjögren's syndrome.
- Diabetes - this is also more common if you have KS.
What is the outlook (prognosis) for Klinefelter's syndrome?
Sometimes boys with KS may struggle through adolescence. They may have difficulties at school, many frustrations and, occasionally, may have serious emotional or behavioural difficulties.
However, the majority of men with KS go on to lead an independent life, forming relationships and getting a normal job. Men with KS have a normal lifespan.
Further reading & references
- Bruining H, Swaab H, Kas M, et al; Psychiatric characteristics in a self-selected sample of boys with Klinefelter syndrome. Pediatrics. 2009 May;123(5):e865-70. Epub 2009 Apr 13.
- Klinefelter syndrome; Genetics Home Reference, 2008
- Chen H; Klinefelter Syndrome, Medscape, Jul 2011
- Blevins CH, Wilson ME; Klinefelter's syndrome. BMJ. 2012 Dec 3;345:e7558. doi: 10.1136/bmj.e7558.
- Paduch DA, Fine RG, Bolyakov A, et al; New concepts in Klinefelter syndrome. Curr Opin Urol. 2008 Nov;18(6):621-7. doi: 10.1097/MOU.0b013e32831367c7.
Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.
Dr Tim Kenny
Dr Colin Tidy
Dr Adrian Bonsall