Klinefelter syndrome (KS) also known as 47,XXY or XXY, is the set of symptoms that result from two or more X chromosomes in males. The primary features are infertility and small testicles. Often, symptoms may be subtle and many people do not realize they are affected. Sometimes, symptoms are more prominent and may include weaker muscles, greater height, poor coordination, less body hair, breast growth, and less interest in sex. Often it is only at puberty that these symptoms are noticed. Intelligence is usually normal; however, reading difficulties and problems with speech are more common. Symptoms are typically more severe if three or more X chromosomes are present (48,XXXY syndrome or 49,XXXXY syndrome).
Klinefelter syndrome usually occurs randomly. An older mother may have a slightly increased risk of a child with KS. The condition is not typically inherited from one’s parents. The underlying mechanisms involves at least one extra X chromosome in addition to a Y chromosome such that the total chromosome number is 47 or more rather than the usual 46. KS is diagnosed by the genetic test known as a karyotype.
While no cure is known, a number of treatments may help. Physical therapy, speech and language therapy, counselling, and adjustments of teaching methods may be useful. Testosterone replacement may be used in those who have significantly lower levels. Enlarged breasts may be removed by surgery. About half of affected males have a chance of fathering children with the help of assisted reproductive technology, but this is expensive and not risk free. Males appear to have a higher risk of breast cancer than typical, but still lower than that of females. People with the condition have a nearly normal life expectancy.
Klinefelter syndrome is one of the most common chromosomal disorders, occurring in one to two per 1,000 live male births. It is named after the endocrinologist Harry Klinefelter, who identified the condition in the 1940s. In 1956, identification of the extra X chromosome was first noticed. Mice can also have the XXY syndrome, making them a useful research model.
The genetic variation is irreversible, but individuals who want to look more masculine can take testosterone. Treating adolescents with implants of controlled-release testosterone has shown good results when appropriately monitored. Hormone therapy is also useful in preventing the onset of osteoporosis.
Often, individuals who have noticeable breast tissue or hypogonadism experience depression and/or social anxiety because they are outside of social norms. An academic term for this is psychosocial morbidity. At least one study indicates that planned and timed support should be provided for young men with KS to ameliorate current poor psychosocial outcomes. The surgical removal of the breasts may be considered for both the psychological reasons and to reduce the risk of breast cancer.
The use of behavioral therapy can mitigate any language disorders, difficulties at school, and socialization. An approach by occupational therapy is useful in children, especially those who have dyspraxia.
By 2010, over 100 successful pregnancies have been reported using IVF technology with surgically removed sperm material from males with KS. Microdissection testicular sperm extraction in adult men with Klinefelter syndrome reported success rates up to 45%.
Children with XXY differ little from other children. Although they can face problems during adolescence, often emotional and behavioral, and difficulties at school, most of them can achieve full independence from their families in adulthood. Most can lead a normal, healthy life.
The results of a study carried out on 87 Australian adults with the syndrome show that those who have had a diagnosis and appropriate treatment from a very young age had a significant benefit compared to those who had been diagnosed in adulthood.
Some research suggests KS substantially decreases life expectancy among affected individuals, though the evidence is not definitive. A 1985 publication identified a greater mortality mainly due to diseases of the aortic valve, development of tumors, and possible subarachnoid hemorrhages, reducing life expectancy by about 5 years. Later studies have reduced this estimated reduction to an average of 2.1 years. These results are still questioned data, are not absolute, and need further testing.
This syndrome, evenly distributed in all ethnic groups, has a prevalence of one to two subjects per every 1000 males in the general population. 3.1% of infertile males have Klinefelter syndrome. The syndrome is also the main cause of male hypogonadism.
According to a 2008 meta-analysis, the prevalence of the syndrome has increased over the past decades; however, this does not appear to be related to increased age of the mother at conception, as no increase was observed in the rates of other trisomies of sex chromosomes (XXX and XYY). The National Institutes of Health, however, state that older mothers might have a slightly increased risk.
The syndrome was named after Harry Klinefelter, who in 1942 worked with Fuller Albright and E. C. Reifenstein at Massachusetts General Hospital in Boston, Massachusetts, and first described it in the same year. The account given by Klinefelter came to be known as Klinefelter syndrome as his name appeared first on the published paper, and seminiferous tubule dysgenesis was no longer used. Considering the names of all three researchers, it is sometimes also called Klinefelter-Reifenstein-Albright syndrome.
In 1956 it was discovered that Klinefelter syndrome resulted from an extra chromosome. Plunkett and Barr found the sex chromatin body in cell nuclei of the body. This was further clarified as XXY in 1959 by Patricia Jacobs and John Anderson Strong.
The first published report of a man with a 47,XXY karyotype was by Patricia Jacobs and John Strong at Western General Hospital in Edinburgh, Scotland, in 1959. This karyotype was found in a 24-year-old man who had signs of KS. Jacobs described her discovery of this first reported human or mammalian chromosome aneuploidy in her 1981 William Allan Memorial Award address.
Klinefelter syndrome can also occur in other animals. In cats it can result in a male tortoiseshell and calico cat (patches of different colored fur), a pattern that is usually only seen in female cats.