47,XXY

Klinefelter's syndrome is a condition caused by a chromosome nondisjunction in males; affected individuals have a pair of X sex chromosomes instead of just one, and is associated with additional risk for some medical conditions. It is named after Dr. Harry Klinefelter, a medical researcher at Massachusetts General Hospital, Boston, Massachusetts, who first described this condition in 1942.

Cause
The XXY chromosome arrangement is one of the most common genetic variations from the XY karyotype, occurring in about 1 in 500 to 1000 male births. Because of the extra chromosome, individuals with the condition are usually referred to as "XXY Males", or "47,XXY Males" rather than as "suffering from Klinefelter's syndrome."

In mammals with more than one X chromosome, the genes on all but one X chromosome are barred from being expressed. This happens in XXY males as well as XX females. A few genes, however, have corresponding genes on the Y chromosome and are not barred. These triploid genes in XXY males may be responsible for symptoms associated with Klinefelter's syndrome.

The first published report (Jacobs & Strong 1959) of a man with a 47,XXY karyotype was by Patricia A. Jacobs and Dr. J.A. Strong at Western General Hospital in Edinburgh, Scotland in 1959. It was found in a 24-year-old man who had signs of Klinefelter syndrome. Dr. Jacobs described her discovery of this first reported human or mammalian chromosome aneuploidy in her 1981 William Allan Memorial Award address (Jacobs 1982).

Signs and symptoms
XXY males are almost always sterile, and some degree of language impairment may be present. In adults, possible characteristics vary widely and include little to no signs of affectedness, a lanky, youthful build and facial appearance, or a rounded body type with some degree of gynecomastia (increased breast tissue). Gynecomastia to some extent is present in about a third of individuals affected, a higher percentage than in the XY population. The far end of the spectrum is also associated with an increased risk of breast cancer, pulmonary disease, varicose veins, diabetes mellitus, rheumatoid arthritis, and osteoporosis, risks shared with women.

Rare X-linked recessive problems occur even more infrequently in XXY males, since these conditions are transmitted by genes on the X chromosome, and people with two X chromosomes are typically carriers rather than affected.

There are many variances within the XXY population, just like in the 46,XY population. While it is possible to characterise 47,XXY males with certain body types, that in itself should not be the method of identification as to whether someone has 47,XXY or not. The only method of identification is karyotype testing.

The condition was first clinically described in 1942 by Klinefelter in Boston. The cause was not found until 1959.

Treatment
The condition is irreversible, but its symptoms can be altered in a number of ways, including testosterone treatment and other therapies.

While the gender identity of people with XXY karyotype is generally stable, it seems people with Klinefelter's suffer from gender identity disorder more often than people without it. However, this observation is based on the reports of support groups for transgender and transsexual people; no scientific study on this subject has been done. The fact that a person undergoing treatment for gender identity disorder has Klinefelter's syndrome is often missed, or the patient is not told, although in many jurisdictions this additional diagnosis can have legal consequences, for example regarding name change or medical treatment having to be adapted.

Inadequately treated hypogonadism in Klinefelter syndrome increases recognized psychosocial morbidity. There is a need for prospectively planned and timed support for young men with Klinefelter syndrome, to ameliorate current poor psychosocial outcomes.

Variations
The 48, XXYY (male) syndrome occurs 1 in 17,000 births and has traditionally been considered to be a variation of Klinefelter's syndrome. XXYY is no longer generally considered a variation of KS, although it has not yet been assigned an ICD-9 code.

Males with Klinefelter syndrome may have a mosaic 47,XXY/46,XY constitutional karyotype and varying degrees of spermatogenic failure. Mosaicism 47,XXY/46,XX with clinical features suggestive of Klinefelter syndrome, is very rare and so far only about 10 cases have been described in literature.