Genetic: Klinefelter Syndrome
Genetic: Klinefelter Syndrome
Causes and Symptoms
For more information
Klinefelter syndrome is a condition caused by one or more extra X chromosomes in males. It is the second most common health condition caused by an extra sex chromosome. Klinefelter syndrome is named for Dr. Harry Fitch Klinefelter (1912–1990), an endocrinologist at Massachusetts General Hospital in Boston, who first described it in 1942. The genetic cause of the syndrome was not discovered until 1959.
Many men with an XXY chromosome arrangement tend to be taller than their father or brothers, to have a rounded body type with a tendency to be overweight, to develop enlarged breasts resembling those of a woman, to have a smaller than average penis and testicles, and to lack facial or body hair. On the other hand, many other men who are XXY do not develop these features; some live out their lives without ever knowing that they have an extra X chromosome. For this reason, many doctors no longer use the term “Klinefelter syndrome” but prefer to describe males with the extra chromosome simply as “XXY males.”
Klinefelter syndrome affects only males. It is thought to occur in one in every 500–1,000 boy babies. About 3,000 affected males are born each
year in the United States. The rate of Klinefelter syndrome is five to twenty times higher in boys with mental retardation than in the general population of newborns. It appears to be equally common in all races and ethnic groups.
Causes and Symptoms
Klinefelter syndrome is caused by a type of genetic error called nondisjunction. Ordinarily, the process of cell division that leads to the formation of germ cells (sperm and eggs) results in a cell with only half the number of chromosomes—twenty-three, instead of forty-six. In nondisjunction, the division of sex chromosomes does not occur, resulting in either an egg with two X chromosomes or a sperm with both an X and a Y chromosome. If a normal sperm carrying a Y sex chromosome fertilizes an egg with two Xs, or a sperm carrying both an X and a Y chromosome fertilizes a normal egg, an XXY male will be conceived. According to researchers, about half the time the extra chromo-some comes from the baby's father and the other half of the time from the mother. A mother who is thirty or older has a slightly increased risk of having an XXY son.
Klinefelter syndrome is characterized by a range of psychosocial as well as physical problems. Not all XXY males will have all these difficulties, and many have them only in mild form.
- Smaller than normal testes and penis, with lower than normal levels of male sexual hormones.
- Thin or absent body and facial hair.
- High-pitched voice.
- Rounded body shape, enlarged breasts, rapid weight gain in adolescence.
- Developmental and learning disabilities. These include delayed speech, difficulty paying attention, mild difficulties with short-term memory, and problems with learning to read.
- Depression and emotional distress caused by low-self-esteem.
- Taller than average height after puberty with disproportionately long arms and legs.
- Infertility (inability to father children).
XXY males are at increased risk of certain autoimmune disorders, including rheumatoid arthritis and lupus. They are also at increased risk of breast cancer and osteoporosis.
Diagnosis of Klinefelter syndrome depends in part on the severity of the patient's symptoms. As has been noted, many XXY males are only mildly affected by their extra X chromosome and may never be diagnosed. Although babies can be diagnosed with the syndrome before birth, the two most common symptoms that bring XXY males to the doctor's office for testing are enlarged breasts and infertility, both of which become matters of concern after puberty. Some XXY boys are diagnosed during the elementary school years because they have speech problems and other learning difficulties.
The diagnosis is made by taking a karyo-type, or chromosome test. To perform a karyo-type, the doctor takes a small sample of the patient's blood. The white blood cells are isolated and cultured in a special solution and examined under a microscope to see what the chromosomes look like.
The doctor may also test a sample of blood for hormone levels. XXY males have low levels of testosterone, a male sex hormone, in their blood serum.
One Man's Story
An XXY male who was born in 1961 and grew up in the 1970s tells about the difference that having a karyotype (chromosome test) made in his life. He was diagnosed with Klinefelter syndrome in junior college. Before his diagnosis, he had problems in school related to low energy levels as well as gaining large amounts of weight: “The major problem faced by me, and by every other Klinefelter's Syndrome victim, is that maturity and learning go from normal to very, very slow after puberty kicks into action. It takes energy to learn, and I didn't have any…. I could not keep up physically, nor could I keep up intellectually. In some things, like computers, I worked well, for I could sit in one place and learn. If I had to move around, go visit the library, do research, exercise, or make any effort at all, I was muted by a weakness that was always labeled as fat and lazy.”
After testosterone therapy, the writer had much more energy, joined his parents in their business for several years, was able to return to college eventually and complete his degree in 2003. He married and was able to lose weight after obesity surgery. He summarizes the benefits of his diagnosis and treatment by reaching out to other XXY males: “I keep meeting people with Klinefelter's who are not taking testosterone and remaining weak and immature in many ways. Don't avoid testosterone. It matured more than my physical form. It matured my mind.”
Treatment of Klinefelter syndrome may involve an educational evaluation as well as medical treatment:
- Hormone injections. Injections of androgens (male sex hormones) are given to XXY males, preferably beginning at puberty, in order to help them gain muscle strength, develop facial hair and a deeper voice, enlarge the testes, raise overall energy levels, and protect against osteoporosis. In many cases hormone treatment improves the boy's mood and self-esteem as well.• Surgery. XXY males with noticeably enlarged breasts may have surgery to remove the extra breast tissue. Surgical treatment reduces the man's risk of breast cancer as well as removing a cause of social embarrassment.
- Speech therapy and language therapy. Most doctors recommend that XXY boys have a complete educational evaluation, preferably in elementary school, so that their learning difficulties (if any) can be treated before they develop behavioral problems or become depressed.
- Physical therapy. Some XXY boys benefit from exercises that help them improve their muscle strength and coordination.
Most doctors consider mid-to-late adolescence the best time to tell an XXY boy about his condition. At that age most are able to understand the cause of the syndrome and its implications, and to decide whether they want to share the information with anyone else.
Most XXY males can live productive lives with normal life expectancy; many complete college and graduate school. In 1996 a technique was developed for extracting sperm from the male testicle and injecting it into a female egg; since that date, at least sixty children around the world have been conceived and born using sperm from men with Kline-felter syndrome. Men who are able to father children this way do not have any greater risk of producing an XXY son than men in the general population.
There is no known way to prevent Klinefelter syndrome because it is caused by a random genetic error.
It is unlikely that Klinefelter syndrome will become more common in the general population in the future because nondisjunction is a random
genetic error. What is likely, however, is that earlier diagnosis and better understanding of the syndrome will help XXY males do well in school and the adult workplace and lower their risk of depression and other setbacks. The knowledge that most XXY males benefit from hormonal treatment, surgery, and various supportive educational measures and can have normal lives is certainly encouraging.
SEE ALSO Breast cancer; Lupus; Osteoporosis; Rheumatoid arthritis
WORDS TO KNOW
Androgen: The generic term for the group of male sex hormones produced by the body.
Germ cell: A cell involved in reproduction. In humans the germ cells are the sperm (male) and egg (female). Unlike other cells in the body, germ cells contain only half the standard number of chromosomes.
Karyotype: A photomicrograph of the chromosomes in a single human cell. Making a karyo-type is one way to test for genetic disorders.
Nondisjunction: A genetic error in which one or more pairs of chromosomes fail to separate during the formation of germ cells, with the result that both chromosomes are carried to one daughter cell and none to the other. If an egg or sperm with a paired set of chromosomes is involved in the conception of a child, the child will have three chromosomes in its genetic makeup, two from one parent and one from the other.
Testosterone: The principal male sex hormone.
For more information
Bock, Robert. Understanding Klinefelter Syndrome: A Guide for XXY Males and Their Families, rev. ed. Bethesda, MD: National Institute of Child Health and Human Development, 2006.
Morales, Ralph. Out of Darkness: An Autobiography: Living with Klinefelter Syndrome. Louisville, KY: Chicago Spectrum Press, 2002.
Brody, Jane. “Personal Health: The Havoc of an Undetected Extra Chromo-some.” New York Times, August 31, 2004. Available online at http://www.query.nytimes.com/gst/fullpage.html?res=9504EEDD1731F932A0575BC0A9629C8B63 (accessed April 6, 2008).
American Association for Klinefelter Syndrome Information and Support(AAKSIS). A Guide to Klinefelter Syndrome. Available online in PDF format at http://www.aaksis.org/Documents2/Klinefelter_Brochure_.pdf (accessed April 6, 2008).
Brager, David. “I'm Not Fat, I'm Deformed: Klinefelter's Syndrome & Me.” David Brager's Homepage. http://www.geocities.com/dibragerowtcom/klinefel.html (accessed April 6, 2008). This is one man's personal account of his life before and after his diagnosis.
Genetics Home Reference. Klinefelter Syndrome. http://www.ghr.nlm.nih.gov/condition=klinefeltersyndrome#resources (accessed April 6, 2008). Knowledge Support and Action (KS&A). Klinefelter Syndrome. http://www.genetic.org/knowledge/support/action/199/ (accessed April 6, 2008). KS&A is a nonprofit organization that was formed in 1989 to help people born with extra X or Y chromosomes. This portion of the KS&A website contains basic information about Klinefelter syndrome as well as links to articles, research reports, and other materials related to the condition.
National Human Genome Research Institute (NHGRI). Learning about Kline-felter Syndrome. http://www.genome.gov/19519068 (accessed April 6, 2008).