What cause klinefelter syndrome?

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Klinefelter Syndrome

Klinefelter syndrome is a group of conditions that affects the health of males who are born with at least one extra X chromosome. Chromosomes, found in all body cells, contain genes. Genes provide specific instructions for body characteristics and functions. For example, some genes determine height and hair color. Other genes influence language skills and reproductive functions. Each person typically has 23 pairs of chromosomes. One of these pairs (sex chromosomes) determines a person’s sex. A baby with two X chromosomes (XX) is female. A baby with one X chromosome and one Y chromosome (XY) is male.

Most males with Klinefelter syndrome, also called XXY males, have two X chromosomes instead of one. The extra X usually occurs in all body cells. Sometimes the extra X only occurs in some cells, resulting in a less severe form of the syndrome. This is called a mosaicism, and is very common. Rarely, a more severe form occurs when there are two or more extra X chromosomes.

What are the signs and symptoms of Klinefelter syndrome?

Signs and symptoms can vary. Some males have no symptoms but a doctor will be able to see subtle physical signs of the syndrome. Many males are not diagnosed until puberty or adulthood. As many as two-thirds of men with the syndrome may never be diagnosed. Many men with mosaicism for XXY males do not have all of the signs and symptoms listed below.

Signs and Symptoms by Age Group

Infants and young boys may have:

  • Problems at birth, such as testicles that haven’t dropped into the scrotum or a hernia*
  • A small penis
  • Weak muscles
  • Speech and language problems, such as delayed speech
  • Problems with learning and reading
  • Problems fitting in socially
  • Mood and behavioral problems

Adolescents may ALSO have:

  • Small, firm testicles
  • Enlarged breasts, called gynecomastia
  • Long legs but a short trunk
  • Above-average height
  • Reduced muscle bulk
  • Sparse facial and body hair
  • Delayed puberty
  • Low energy levels

Adults may ALSO have:

  • Low testosterone (male hormone) levels
  • Infertility from a lack of sperm
  • Decreased sex drive
  • Problems getting or keeping an erection
  • Other difficulties, such as being unable to make plans or solve problems

* when an internal organ bulges through a body cavity wall

How is Klinefelter syndrome diagnosed?

Diagnosis is based on a physical examination, hormone testing, and chromosome analysis. The syndrome can also be diagnosed before birth but testing is not routinely done at that time.

Health Problems Associated with Klinefelter Syndrome

Klinefelter syndrome can lead to weak bones (osteoporosis), varicose veins, and autoimmune diseases (when the immune system acts against the body), such as lupus or rheumatoid arthritis. XXY males have an increased risk for breast cancer and cancers that affect blood, bone marrow, or lymph nodes, such as leukemia. They also tend to have excess fat around the abdomen (which raises the risk of health problems), heart and blood vessel disease, and type 2 diabetes.

What is the treatment for Klinefelter syndrome?

Treatment can help males overcome many of the physical, social, and learning problems that are part of the syndrome. Males with Klinefelter syndrome should be seen by a team of health care providers. The team may include endocrinologists, general practitioners, pediatricians, urologists, speech therapists, genetic counselors, and psychologists. Surgery may be needed to reduce breast size. With treatment, men can lead very normal lives.

Experts recommend testosterone replacement, starting during puberty, for proper development of muscles, bones, male sex characteristics such as facial hair, and sexual function. Continued treatment throughout life helps prevent long-term health problems. Testosterone replacement does not cure infertility, however. Infertility treatments require specialized—and costly—techniques, but some men with Klinefelter syndrome have been able to father children.

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What Is Klinefelter Syndrome?

Klinefelter syndrome can cause problems with learning and sexual development in guys. It’s a genetic condition (meaning a person is born with it).

Klinefelter syndrome only affects males. It happens because of a difference deep inside the body’s cells, in microscopic strings of DNA (what make up genes) called chromosomes. Chromosomes are tiny, but they play a huge role in who we are — including deciding our gender, how we look, and how we grow.

Doctors sometimes call Klinefelter syndrome “XXY.” Instead of one X and one Y chromosome like most guys have, guys with Klinefelter syndrome are born with an extra “X” chromosome in most or all of their cells.

When puberty starts and guys’ bodies begin to make sex hormones, boys with Klinefelter usually don’t produce as much of the male hormone testosterone. That doesn’t make a guy less male, but it can affect things like penis and testicle growth, and growth of body hair and muscles. Boys with Klinefelter syndrome may also have problems with attention, speech development, and learning word skills like spelling, reading, or writing.

Doctors think Klinefelter syndrome is fairly common. Most boys who have it go on to have a good and healthy life, especially if they get the help they need from doctors, speech therapists, and other experts.

What Causes Klinefelter Syndrome?

Klinefelter syndrome isn’t passed down through families like some genetic diseases. Instead, it happens randomly from an error in cell division when a parent’s reproductive cells are being formed. If one of these cells is part of a successful pregnancy, a baby boy will have the XXY condition.

The XXY condition can affect some or all of the body’s cells. If only some cells have the extra X chromosome, it’s called mosaic Klinefelter syndrome. Guys with this condition often have milder signs and symptoms. Some may not even know they have Klinefelter syndrome until later in life. Other boys have more than two X chromosomes. Their condition may be more severe.

What Are the Signs & Symptoms of Klinefelter Syndrome?

Differences in boys with Klinefelter syndrome can range from mild to severe. Some guys have few or no obvious signs. Other times, Klinefelter syndrome interferes with speech, learning, and development.

Boys with Klinefelter syndrome might have some or all of these physical signs:

  • a taller, less muscular body than other boys their age
  • broader hips and longer legs and arms
  • larger breasts (gynecomastia)
  • weaker bones
  • a lower energy level
  • smaller penis and testicles
  • delayed puberty or only going through puberty partway (or, in rare cases, not at all)
  • less facial and body hair following puberty

Boys with Klinefelter syndrome may have difficulty with spelling, reading, writing, and paying attention. They may tend to be quiet, shy, and more reserved or sensitive than other guys. Some boys with Klinefelter syndrome are less interested in sports or physical activities.

Since high-school life often revolves around schoolwork and sports, guys with Klinefelter may feel like they don’t fit in or lack self-confidence. But, as men, most have normal friendships and relationships.

What Problems Can Happen?

Most teens with Klinefelter syndrome aren’t likely to have major health problems. But the condition can bring challenges later in life. For example, guys with Klinefelter syndrome may be more likely to get some types of cancer and other diseases, like type 2 diabetes and osteoporosis, a condition where the bones become weaker later in life.

As men, most guys with Klinefelter syndrome can have sex, usually with the help of testosterone treatment. But problems with their testicles prevent them from making enough normal sperm to father children. Fertility researchers are working on new treatments. By the time a teen with Klinefelter syndrome is ready to become a dad, there may be new options available related to the extraction of sperm from the testicles.

How Is Klinefelter Syndrome Diagnosed?

The earlier a guy finds out about Klinefelter syndrome, the better. Treatments are most effective if they start while a guy is still young. So if you’re worried about your development, talk to your doctor. It might be nothing, but it’s always best to know, especially because Klinefelter syndrome can be hard to notice.

To diagnose a guy with Klinefelter syndrome, doctors usually begin by asking about any learning or behavior issues and examining his testicles and body proportions. If the signs point toward the condition, doctors will order one or both of these two types of tests:

  1. Hormone testing. This test checks for abnormal hormone levels that can result from the XXY condition. It is usually done with a blood sample.
  2. Chromosome analysis. This test is also called a karyotype analysis. It checks for the XXY condition by looking at the number of chromosomes. The test is usually done using a blood sample.

How Is Klinefelter Syndrome Treated?

There’s no way to change the XXY condition if someone is born with it, but there are treatments that can help. Beginning treatment early makes it work better.

  • Testosterone replacement therapy (TRT) works by increasing a guy’s testosterone levels into the normal range. This can help someone with Klinefelter syndrome develop bigger muscles, a deeper voice, growth of the penis, and facial and body hair. It also can help improve bone density and reduce any breast growth. However, testosterone therapy cannot increase testicle size or prevent or reverse infertility.
  • Physical therapy, occupational therapy, and speech therapy can build muscle strength and coordination as well as help guys improve their speaking, reading, and writing skills.

Looking Ahead

It’s not easy to feel like you’re developing differently from other guys. Guys with Klinefelter syndrome are more likely to have low self-confidence or shyness, which can make things harder. Counselors and therapists can give guys practical skills to help them feel more confident in social settings.

If you’re struggling to keep up or do well in school, talk to your school counselor or teachers. Tell them about your condition. You might be able to get extra assistance and support to make schoolwork and classes go more smoothly.

Reviewed by: Judith L. Ross, MD Date reviewed: September 2017

Klinefelter syndrome: What you need to know

Chromosomal abnormalities due to KS cannot be corrected, and there is no cure. However, treatment can be effective in reducing symptoms.

While early diagnosis will help manage some of the chronic aspects of KS, it is never too late to start treatment for KS. Treatment can bring benefits at any age and may include the following:

Testosterone replacement therapy

Treatment is usually in the form of an injection, pills, gel, or a patch. Testosterone replacement therapy improves, strength, body hair growth, energy, and concentration.

Starting treatment early, usually at the onset of puberty, can prevent the long-term effects of reduced testosterone production.

Testosterone therapy does not improve testicle size or fertility.

Fertility treatment

Between 95 and 99 percent of males with KS are infertile because they do not produce enough sperm to fertilize an egg. However, more than 50 percent of males with KS do have sperm.

For men with minimal sperm production, an intracytoplasmic sperm injection (ICSI) can be effective. During an ICSI, sperm is removed from the testicle and injected directly into the egg.

If diagnosed early enough, semen or testicular tissue can be preserved before the testicular damage starts, probably at puberty. This method is called cryopreservation, and it uses very low temperatures to preserve living cells and tissues for later use.

Breast reduction surgery

There is no approved drug treatment for overdeveloped breast tissue in males. Removal of the breast tissue by a plastic surgeon is effective but comes with the risks associated with any surgery.

The result of breast reduction surgery is a chest that appears typically more masculine. It reduces the chances of developing breast cancer and can help alleviate the social stress associated with enlarged breasts in males.

Psychological counseling

Dealing with the symptoms of KS can be embarrassing and challenging for males, especially during puberty and early adulthood.

Coping with infertility can also be difficult, and a counselor or psychologist can help people to process and reduce emotional issues associated with KS.

Share on PinterestPsychological counseling and speech therapy may be helpful to those living with KS.

Therapeutic support

The right support at the right time can help prevent difficulties with language, schooling, and social interaction. Additional therapeutic support may include:

  • speech and physical therapy
  • educational evaluation and support
  • occupational therapy
  • behavioral therapy

Physician Update – New Hope for Those with Klinefelter Syndrome

New Hope for Those with Klinefelter Syndrome

Date: September 20, 2013

Klinefelter Syndrome Center Director Adrian Dobs meets with psychiatrist Cynthia Munro to discuss a patient.

Boys and men with the chromosomal disorder Klinefelter syndrome, or XXY male, have a new resource for treatment and medical management.

The Johns Hopkins Klinefelter Syndrome Center is the only multidisciplinary program of its kind in the country serving adult males, says endocrinologist Adrian Dobs, the center’s director. (A comprehensive clinic in Colorado is dedicated solely to children with the syndrome.)

One in every 750 males is born with an extra X chromosome. This can lead to a range of health issues seen in Klinefelter syndrome, including infertility, underdeveloped genitals and learning disabilities. The condition has been linked to increased risk for depression and autoimmune disorders, like lupus and rheumatoid arthritis. Affected males are also at higher risk for breast and blood cancers.

“There’s a real gap in the care of men with Klinefelter syndrome,” says Dobs. “These men are complicated, and many are not diagnosed until puberty or adulthood, she says. Up to two-thirds of men with the syndrome are never diagnosed.

A Multidisciplinary Approach to Klinefelter’s Syndrome

At the center, all patients see Dobs initially for a complete medical history, exam and discussion about hormone treatment. Then the clinic can coordinate appointments with Hopkins experts in pediatrics, primary care, genetic counseling, urology, neuropsychology (for problems with learning, thinking or mood), and psychology (for gender identity issues).

Testosterone replacement therapy, when started in adolescence, can help ensure proper development of muscles, bones and male sex characteristics, Dobs says. For men interested in fertility preservation, other approaches to hormone therapy should be considered. Infertile men can often father children via assisted reproduction.

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What is Klinefelter syndrome?

Klinefelter syndrome is one of the most common chromosomal disorders, affecting 1/500 to 1/1,000 newborn males. Chromosomes, found in all body cells, contain genes. Genes provide specific instructions for body characteristics and functions. Each person typically has 23 pairs of chromosomes. One of these pairs (sex chromosomes) determines a person’s sex. A baby with two X chromosomes (XX) is female. A baby with one X chromosome and one Y chromosome (XY) is male.

Males with Klinefelter syndrome, may have two or more X chromosomes instead of one. The extra X chromosomes usually occur in all body cells. Sometimes the extra X chromosomes only occur in some cells (mosaic.)

What causes Klinefelter syndrome?

The syndrome is not inherited from the parents. The addition occurs in the sperm, the egg, or after conception.

Signs and symptoms can vary. Many males are not diagnosed until puberty or adulthood. As many as two-thirds of men with the syndrome may never be diagnosed. Symptoms that may occur include: delayed, absent, or incomplete puberty, breast growth (gynecomastia), small testes and penis, less muscle development and hair growth, longer legs compared to torso, learning disabilities, fertility issues

Klinefelter syndrome can lead to weak bones (osteoporosis), varicose veins, and autoimmune diseases (when the immune system acts against the body), such as lupus or rheumatoid arthritis. XXY males have an increased risk for breast cancer and cancers that affect blood, bone marrow, or lymph nodes, such as leukemia. They also tend to have excess fat around the abdomen (which raises the risk of health problems), heart and blood vessel disease, and type 2 diabetes.

How is Klinefelter syndrome diagnosed?
Diagnosis is based on a physical examination, hormone testing, and chromosome analysis. The syndrome can also be diagnosed before birth, but testing is not routinely done at that time.

Treatment of Klinefelter syndrome may include:

  • Genetic counseling to discuss long-term complications
  • Special education programs (including speech therapy, occupational therapy, or other therapies)
  • Testosterone therapy
  • Counseling for behavioral and learning issues
  • Infertility treatments, if desired

Questions to ask your doctor

  1. Will diagnostic tests and treatment be covered by my insurance?
  2. What are my (or my child’s) options for testosterone therapy?
  3. What are the benefits and risks?
  4. What can I do manage other health problems linked to Klinefelter syndrome?
  5. Will I (or my child) be able to have children?
  6. Will I (or my child) have normal sexual function?

Rare Disease Database

TEXTBOOK
Samango-Sprouse, C, and Gropman, AL. X & Y chromosomal variations: hormones, brain development, and neurodevelopmental performance. San Rafael, CA: Morgan & Claypool Publishers, 2017.

Samango‐Sprouse C, Stapleton EJ, Lawson P, Mitchell F, Sadeghin T, Powell S, Gropman AL. Positive effects of early androgen therapy on the behavioral phenotype of boys with 47, XXY. American Journal of Medical Genetics Part C: Seminars in Medical Genetics 2015 Jun 1 (Vol. 169, No. 2, pp. 150-157.

Wosnitzer, M S and Paduch, D A., Endocrinological issues and hormonal manipulation in children and men with Klinefelter syndrome. Am. J. Med. Genet. 2013;163: 16–26.

Samango-Sprouse CA, Gropman AL, Sadeghin T, et al. Effects of short-course androgen therapy on the neurodevelopmental profile of infants and children with 49,XXXXY syndrome. Acta Paediatr. 2011;100(6):861-5.

Samango-Sprouse CA. Expansion of the phenotypic profile of the young child with XXY. Pediatr Endocrinol Rev. 2010;8 Suppl 1:160-8.

Visootsak J, Graham JM Jr. Klinefelter syndrome and other sex chromosomal aneuploidies. Orphanet J Rare Dis. 2006;1:42.

Wikstrom AM, Painter JN, Raivio T, Aittomaki K, Dunkel L. Genetic features of the X chromosome affect pubertal development and testicular degeneration in adolescent boys with Klinefelter syndrome. Clin Endocrinol (Oxf). 2006;65(1):92-7.

Schiff JD, Palermo GD, Veeck LL, et al. Success of testicular sperm injection and intracytoplasmic sperm injection in men with Klinefelter syndrome. J Clin Endocrinol Metab. 2005;90(11):6263-7.

Swerdlow AJ, Higgins CD, Schoemaker MJ, et al. Mortality in patients with Klinefelter syndrome in Britain: a cohort study. J Clin Endocrinol Metab. 2005;90(12):6516-22.

Swerdlow AJ, Schoemaker MJ, Higgins CD, Wright AF, Jacobs PA. Cancer incidence and mortality in men with Klinefelter syndrome: a cohort study. J Natl Cancer Inst. 2005;97(16):1204-10.

Wattendorf DJ, Muenke M. Klinefelter syndrome. Am Fam Physician. 2005;72(11):2259- 62.

Bojesen A, Juul S, Gravholt CH. Prenatal and postnatal prevalence of Klinefelter syndrome: a national registry study. J Clin Endocrinol Metab. 2003;88(2):622-6.

Kamischke A, Baumgardt A, Horst J, Nieschlag E. Clinical and diagnostic features of patients with suspected klinefelter syndrome. J Androl. 2003;24(1):41-8.

Linden MG, Bender BG, Robinson A. Sex chromosome tetrasomy and pentasomy. Pediatrics. 1995;96(4 Pt 1):672-82.

Evans JA, de von Flindt R, Greenberg C, Ramsay S, Hamerton JL. A cytogenetic survey of 14,069 newborn infants. IV. Further follow-up on the children with sex chromosome anomalies. Birth defects original article series. 1981 Dec;18(4):169-84.

What Is Klinefelter syndrome (XXY)?

Also known as XXY syndrome, this chromosomal condition affects only males.

A common genetic chromosomal condition, Klinefelter syndrome occurs when a boy is born with an extra copy of the X chromosome.

Klinefelter syndrome can affect both physical and cognitive development.

According to the National Human Genome Research Institute, Klinefelter syndrome is found in about 1 out of every 500 to 1,000 newborn males.

Klinefelter Syndrome Causes

Klinefelter syndrome occurs as the result of a random genetic error during the formation of the egg or sperm or after conception.

The syndrome is not the result of something the parents did or did not do.

However, women who become pregnant after 35 years of age have a slightly increased risk of having a boy with Klinefelter syndrome.

People normally have 46 chromosomes in each cell. Two of those 46 chromosomes, known as X and Y, are called sex chromosomes because they help determine whether a person will develop male or female sex characteristics.

Females usually have two X chromosomes, while males have one X chromosome and one Y chromosome.

However, Klinefelter syndrome occurs because of one extra copy of the X chromosome in each cell (XXY).

Some males with Klinefelter syndrome have the extra X chromosome only in some of their cells. When this occurs it is called mosaic Klinefelter syndrome.

While rare, a more severe form of Klinefelter can occur if a male has more than one extra copy of the X chromosome.

Klinefelter Syndrome Symptoms

The most common symptom of Klinefelter syndrome is infertility, which often isn’t noticed until adulthood.

Klinefelter syndrome adversely affects testicular growth, resulting in smaller than normal testicles, which often leads to low production of testosterone.

Although most men with Klinefelter syndrome produce little or no sperm, reproductive procedures may make it possible for some men with the condition to father children.

The effects of Klinefelter syndrome vary from person to person, and signs and symptoms of the syndrome can appear differently at different ages.

Symptoms in babies:

  • Weak muscles
  • Slow motor development of things like sitting up, crawling, and walking
  • Speech delay
  • Docile personality
  • Testicles that haven’t descended into the scrotum

Symptoms in boys and teenagers:

  • Taller than average stature
  • Longer legs, shorter torso, and broader hips
  • Absent, delayed, or incomplete puberty
  • Less-muscular bodies and less facial and body hair after puberty
  • Small, firm testicles
  • Small penis
  • Enlarged breast tissue
  • Weak bones
  • Low energy levels
  • Shyness
  • Difficulty expressing feelings or socializing
  • Problems with reading, writing, spelling, or math
  • Difficulty being attentive

Symptoms in men:

  • Infertility
  • Small testicles and penis
  • Taller than average stature
  • Weak bones (osteoporosis)
  • Decreased facial and body hair
  • Enlarged breast tissue
  • Decreased sex drive

Complications

Men with Klinefelter syndrome may be at increased risk for the following:

  • Varicose veins and other problems with blood vessels
  • Breast cancer and cancers of the blood, bone marrow, or lymph nodes
  • Lung disease
  • Autoimmune disorders, such as type 1 diabetes and lupus
  • Belly fat, which can lead to other health problems
  • Testosterone replacement therapy can reduce the risk of the health problems listed above, especially when therapy is started at the onset of puberty.

Klinefelter Syndrome Diagnosis

If you suspect that you or your son may have Klinefelter syndrome, your doctor will examine your (or your son’s) genital area and chest, as well as conduct tests to check reflexes and mental functioning.

Additionally, the following tests are used to diagnose Klinefelter Syndrome:

Chromosomal analysis: Also called karyotype, this involves drawing a small sample of blood, which is sent to a lab to check the shape and number of chromosomes.

Hormone testing: This can be done through blood or urine samples and can detect if abnormal sex hormone levels — a sign of Klinefelter syndrome — are present.

Klinefelter Syndrome Treatment

While there is no cure for sex chromosome changes caused by Klinefelter syndrome, treatments can help minimize effects, especially when they’re started early. Treatment may include the following.

Testosterone replacement therapy: Since males with Klinefelter syndrome don’t produce enough testosterone, undergoing testosterone replacement therapy at the onset of puberty can allow a boy to undergo the body changes that normally occur at puberty, such as developing a deeper voice, growing facial and body hair, and increasing muscle mass and penis size.

Testosterone therapy can also improve bone density and reduce the risk of fractures, but it will not enlarge the testicles or help with infertility.

Testosterone may be given as an injection or with a gel or patch on the skin.

Fertility treatments: Intracytoplasmic sperm injection (ICSI) can help men with minimal sperm production by removing sperm from the testicle and injecting it directly into a woman’s egg.

Breast tissue removal: For those who develop enlarged breasts, excess breast tissue can be removed with plastic surgery.

Educational support: Teachers, school counselors, or school nurses may be able to help with finding extra support for learning.

Speech and physical therapy: These can help overcome problems with speech, language, and muscle weakness.

Psychological counseling: Whether from a family therapist, counselor, or psychologist, counseling can help people with Klinefelter syndrome work through emotional issues related to puberty, young adulthood, and infertility.

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