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.
During stage I or II of 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 from only 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 (about 10%) 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.
Signs and Symptoms
The phenotype of the affected person is basically male, tall stature with elongated lower legs and forearms. The body shape, however, is more feminine (narrow shoulders, broad hips) 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 is also increased.
One of the main symptoms of this condition is infertility that arises in the beginning of the third decade at its latest. The infertility is a result of atrophy of the seminiferous tubules. The testicles and penis of an affected man are small (< 10 mL, 2 cm), and the individual also express low libido and impotence.
As noted above, fertility is very rare in cases of Klinefelter syndrome, and it usually ceases in the beginning of the third decade when testicles are increasingliy hyalinized.
The IQ can be reduced by 10–15 points. However, mental retardation is not a stable clinical feature of Klinefelter syndrome.
- reduced hair growth in pubic region, axillary region, chest and face;
- varicose veins and leg ulcers;
- diabetes mellitus in 8% of cases;
- thyroid gland problems are common;
- lung disease.
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.
Klinefelter syndrome affects worldwide every 1/500 to 1/1000 male births.
Life expectancy is normal, yet the morbidity and mortality tends to be higher.
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).
- Genetics Home Reference. Klinefelter syndrome [online]. The last revision 2008-07, [cit. 2011-01-15]. <http://ghr.nlm.nih.gov/condition/klinefelter-syndrome>.
- MedLine Plus. Klinefelter syndrome [online]. U.S. National Library of Medicine / National Institute of Health, The last revision 2010-11-1, [cit. 2011-01-15]. <http://www.nlm.nih.gov/medlineplus/ency/article/000382.htm>.
- PRITCHARD, Dorian J – KORF, Bruce R. Medical Genetics at a Glance. 2. edition. Wiley-Blackwell, 2007. 168 pp. ISBN 978-1405148467.