47, XXY (Klinefelter syndrome)
What is 47, XXY (Klinefelter syndrome)?
47, XXY (or XXY) is a genetic condition caused when someone has two X chromosomes and one Y chromosome. Males normally have an X chromosome and a Y chromosome (46, XY), and females normally have two X chromosomes (46, XX).
Because people with an XXY chromosome arrangement have a Y chromosome, they are considered genetic males. Most XXY individuals develop as males, often not knowing they have an extra chromosome. Some will develop the varied and often subtle characteristics associated with Klinefelter syndrome. And a small proportion will develop as intersex (between male and female) or female. Physical characteristics may appear around the time of puberty, when gender identity and sexual characteristics begin to take shape.
Similar conditions are caused by additional X chromosomes (48, XXXY; 49, XXXXY), but they are much more rare. The more X chromosomes a person has, the stronger the physical characteristics and health problems tend to be, including intellectual disability.
How do people get 47, XXY (Klinefelter syndrome)?
XXY is usually caused by what is called nondisjunction. Nondisjunction happens when a pair of sex chromosomes fails to separate during egg (or sperm) formation. When an egg (or sperm) with an extra X chromosomes joins with a normal sperm (or egg), the resulting embryo will end up with three sex chromosomes (XXY) instead of the normal two (XX or XY). As the baby develops, the extra chromosome is then copied in every cell.
Nondisjunction leading to XXY is equally likely to happen in the mother's egg and the father's sperm. In about 10% of cases, chromosomes fail to separate when a cell divides very early in embryonic development, and only some of the baby's cells have an extra X chromosome. Such "mosaic" cases are usually mild and often remain undetected.
What are the symptoms of 47, XXY (Klinefelter syndrome)?
The XXY chromosome arrangement affects primarily sexual development. Typically, testes don't fully develop, and the levels of the hormone testosterone (important for male sexual development) are lower than average. As adults, nearly all XXY males are unable to make sperm and so cannot have biological children. Many men discover their condition only after they seek medical help for infertility.
The symptoms of XXY (Klinefelter syndrome) can be very subtle and are highly varied. Children and adults may be taller than average, with proportionally longer arms and legs, and they may have less-muscular bodies, more belly fat, wider hips, narrower shoulders, or minor to moderate learning disabilities. Changes that appear at puberty can include low growth of facial and body hair, development of breast tissue, and small testes.
XXY individuals are also more likely to develop certain medical conditions, including osteoporosis (weak bones), varicose veins, type 2 diabetes, and heart valve defects. As adults, they are just as likely as XX females to develop breast cancer and certain autoimmune disorders.
How do doctors diagnose 47, XXY (Klinefelter syndrome)?
If a doctor suspects that an individual may be XXY (based on physical characteristics, most commonly infertility), the diagnosis can be made using a karyotype. A karyotype is an analysis of a patient's chromosomes taken from a blood sample.
XXY may also be diagnosed during a woman's pregnancy. Doctors can look for chromosome abnormalities in cells taken from the amniotic fluid surrounding the fetus (amniocentesis) or from the placenta (chorionic villus sampling, or CVS). About 10% of cases are diagnosed this way.
As many as 75% of XXY individuals are never diagnosed.
How is 47, XXY (Klinefelter syndrome) treated?
Knowing an individual's chromosomal status is important for both their physical and emotional health. Early diagnosis can alert doctors to the need for bone-density and hormone-level monitoring. Educators can be on the lookout for learning disabilities. XXY individuals also may need emotional support and counseling, especially during puberty. Boys who develop breast tissue or who do not develop facial or body hair may feel self-conscious. Teens may need support as they face gender identity issues.
Teens and adults who wish to be treated can be given hormones. The hormone testosterone will help them develop more typically male characteristics, and estrogen will help them develop more typically female characteristics. Those who choose can have surgery to remove breast tissue.
Many 47, XXY individuals are quite typical males who receive no treatment. Those who wish to have children can often be helped with reproductive technologies.
Interesting facts about 47, XXY (Klinefelter syndrome)
XXY is one of the most common genetic conditions, affecting about 1 in 660 genetic males.
Klinefelter syndrome is named for Dr. Harry Klinefelter, who first reported its symptoms in 1942.