Klinefelter Syndrome

Klinefelter syndrome, 47,XXY, or XXY syndrome is a condition where human males have an extra X chromosome.

Males normally have a chromosomal makeup of XY, but an affected individual with Klinefelter syndrome will have at least two X chromosomes and at least one Y chromosome.

The syndrome was named after Dr. Harry F. Klinefelter, who was an American rheumatologist and endocrinologist. Between 1941 and 1942, Klinefelter went for one year to Boston to work at the Massachusetts General Hospital. It was here, under the supervision of Fuller Albright, that the syndrome was first described in 1942.

Genetics
During meiosis (sex cell division) a nondisjunction can occur which retains the extra X chromosome and cause the Klinefelter syndrome.

Mammals normally have more than one X chromosome, but the genes on all but one is expressed. This is due to X-inactivation. This is a natural process which can be seen in female mammals, XX. In the XXY male, a few genes located in the pseudoautosomal regions of their X chromosomes, have corresponding genes on their Y chromosomes and are capable of being expressed. These triploid genes present in cells of male, may be what is causing the symptoms for Klinefelter syndrome.

Some males have only the extra X chromosome present in some of their cells. This is described as mosaic Klinefelter syndrome, and can be described with some variant of mosaic karyotype (e.g. 46,XY/47,XXY). This means that some of the cells from an affected individual will show a normal karyotype, while other cells can show the karyotype of Klinefelter syndrome. These individuals usually show milder signs and symptoms of the condition, but this again depends on the number of cells expressing the affected trait.

Body form
The phenotype of a male affected is basically male, tall stature with elongated lower legs and forearms. The body shape, however, is more feminine with a lower muscle mass. One third of affected individuals show gynaecomastia (abnormal development of mammary glands in male resulting in breast enlargement). The risk for male breast cancer and osteoporosis also increase.

Fertility
One of the main symptoms of this condition is infertility. The testes of these individuals are often small and soft (<10 mL, 2cm). The infertility is a result of atrophy of the seminiferous tubules. The testicles and penis of an affected man is small, and the individual also express low libido and impotence.

IQ
The IQ can be reduced by 10-15 points. However, mental retardation is not a stable clinical feature of Klinefelter syndrome.

Other features

 * Reduced normal hair growth in pubic region, axillary region, chest and face.
 * Varicose veins and leg ulcers
 * Diabetes mellitus in 8% of cases
 * Thyroid problems are common
 * Depression
 * Lung disease

Diagnosis
Most common method for confirming the diagnosis is standard karyotyping. This procedure is done to see wether the patient has a presence of extra X chromosome. A positive karyotype would be 47,XXY; 48,XXXY; 49,XXXXY etc.

Prenatal testing can also be performed. Chorionic villi sampling and amniocentesis are two common methods where the foetus tissue is extracted and their DNA is isolated and genetically tested for abnormalities.

Other tests that can be performed includes; semen count; and blood tests checking hormone levels.

Frequency
Klinefelter syndrome affects worldwide every 1/500 to 1/10000 male births.

Treatment
Life expectancy is normal, but 50% die before birth.

The genetic disorder itself is irreversible. But testosterone therapy has shown to help with gaining a more masculine appearance:
 * Increased body hair growth
 * Increased muscle tone and mass
 * Increased energy and sexual drive
 * Increased mood and general self esteem
 * Also show to increase cognitive concentration

Since most affected individuals can not make a woman pregnant, assisted reproduction specialists are available for help (IVF using sperm from the donor).

Resources

 * http://ghr.nlm.nih.gov/condition/klinefelter-syndrome
 * http://www.nlm.nih.gov/medlineplus/ency/article/000382.htm
 * Pritchard, D. J., and Bruce R. Korf. Medical Genetics at a Glance. Malden, MA: Blackwell Pub., 2008. Print.