Klinefelter Syndrome

Updated August 5, 2019

This article was scientifically reviewed by Brenna Bentley

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A list of references is also included at the bottom of this article.

The first medical description of Klinefelter syndrome was in 1942. Since that time, doctors and researchers have come to learn it’s the most common chromosomal abnormality affecting newborn males.

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Disclaimer: Before You Read

It is important to know that your genes are not your destiny. There are various environmental and genetic factors working together to shape you. No matter your genetic makeup, maintain ideal blood pressure and glucose levels, avoid harmful alcohol intake, exercise regularly, get regular sleep. And for goodness sake, don't smoke.

Genetics is a quickly changing topic. Read More...

One of the most interesting facts about Klinefelter syndrome is that the condition can also occur in wild and domesticated animals.

Here at YourDNA.com, if you or a loved one are facing a Klinefelter syndrome diagnosis, we know you have questions and you need answers fast.

That's why we've done the research. We want you to have one resource to turn to for facts presented in such a way that they are easy to understand.

If You or a Loved One Was Diagnosed With Klinefelter Syndrome, Know This . . .

Receiving a diagnosis of Klinefelter Syndrome might be surprising. If you are a parent of a child recently diagnosed you might be wondering what the future holds. If you are an adult receiving this diagnosis you might wonder how you did not know.

Let us start by saying, Klinefelter is no one's fault. There is not anything someone did or did not do to cause this. Most individuals with this condition live their whole lives without receiving a diagnosis. 

Additionally,  you are also not alone. There is a large community of families with this condition who can provide guidance and support.

Most individuals with this condition will lead healthy and meaningful lives. Take your time moving through the sections and feel free to read it a few times.

What Is Klinefelter Syndrome?

Everyone is born with 23 pairs of chromosomes in every cell (46 chromosomes total). The last pair of is the X and Y sex chromosomes that determine male and female biological sex, most notably the development of reproductive organs.

When we focus on the sex chromosomes, we see that typically women have two X chromosomes and men have an X and a Y chromosome. 

Klinefelter syndrome is considered to be a rare disease. It is a genetic condition in which males are born with one or more extra X chromosomes.

This could mean their sex chromosomes could be XXY, XXXY, XXXXY, or something along those lines.

All individuals with Klinefelter Syndrome will have a Y chromosome which means they will all be males. 

In about 10% of cases, only some of the cells have an extra X chromosome, this is said to be mosaic Klinefelter Syndrome, and it tends to have milder symptoms.

It’s also commonly referred to as XXY syndrome or 47, XXY. People with the condition are sometimes referred to as X chromatin positive males.

Signs & Symptoms of Klinefelter Syndrome 

The signs and symptoms of Klinefelter syndrome vary from person to person. The severity of symptoms depends on how many X chromosomes are present. Individuals with more X chromosomes tend to experience more symptoms.

For most individuals with Klinefelter Syndrome, the signs and symptoms tend to be mild, often going undiagnosed until puberty or adulthood. This is because the most common symptom associated with this condition is infertility, occuring in 90% of cases.

Specifically, infertility is due to a low sperm count or a complete lack of sperm. However, new studies have found that with the help of assisted reproductive therapy, some individuals with Klinefelter Syndrome can father children. 

When a child is born with Klinefelter Syndrome, they will likely look just like any newborn baby. Sometimes the child might have a small penis, small testicles (hypogonadism), undescended testicles, or a small opening on the underside of the penis. However, these symptoms do not occur in everyone with this condition. 

As the child moves into childhood, other symptoms may arise.1 Individuals with this condition tend to be taller than average, have more fat around their stomach (abdominal adiposity) and might have a curved pinky finger or flat feet.

Some children experience the under development of their skeletal muscle which could lead to a delay in their motor development. When they enter school they might experience some learning disabilities such as mild delays in their speech and language development or difficulty reading. 

Once the child reaches puberty other physical signs can appear often due to low levels of testosterone. They include:

  • Small testes (second most common symptom, occurring in 95% of cases)
  • Elevated gonadotropin levels

  • Azoospermia

  • Low testosterone levels

  • Smaller penis

  • Less muscle tone

  • Weaker bones

  • Narrower shoulders

  • Wider hips

  • Increase in breast tissue (gynecomastia) 

  • Less Facial Hair and Body Hair

  • Low energy

  • Metabolic syndrome

  • Undescended testes

  • Congenital malformations

  • Hypothyroidism 

As boys get older they may also find that they have a low or decreased sex drive.

Additionally, individuals with Klinefelter Syndrome may struggle with mental health. Some may develop anxiety, depression, behavioral problems, or experience difficulty with social skills or attention.

Can Klinefelter Syndrome Lead To Other Conditions? 

Can males with Klinefelter syndrome have babies? It’s a question that many men ask after being diagnosed.

In many cases, men with Klinefelter syndrome can’t father a child naturally on their own. There are treatment options to help men overcome the obstacles of low sperm count, but they are not always successful.

There’s also an increased frequency of other diseases and medical conditions associated with Klinefelter syndrome.

Approximately 50% of individuals with Klinefelter Syndrome will develop metabolic syndrome which is a combination of at least three of the following: Type 2 diabetes, high blood pressure, increased belly fat, high cholesterol and triglycerides. It’s estimated that 10-39% of men with Klinefelter have type 2 diabetes.

Individuals with this condition are also at an increased risk to develop autoimmune disorders such as rheumatoid arthritis, systemic lupus, and Sjogren Syndrome.  

Mitral valve prolapse tends to occur more commonly in individuals with Klinefelter Syndrome than those without, however this heart condition may pose no medical problems, or it could be severe enough to require surgery. 

Fractures are another regular occurrence due to weakened bones (osteoporosis). Boys and men with Klinefelter syndrome have a 2-40 fold increased risk of getting a bone fracture.

Additionally, individuals are at an increased risk for breast cancer, lung disease, and varicose veins. 

Upwards of 75% of children with it have a learning disability. Boys with Klinefelter syndrome may also have difficulty fitting in socially and interacting with their peers as personality traits often include being shy and quiet.

Additionally, up to 1 in 4 children with Klinefelter syndrome are diagnosed with a psychiatric disturbance.

Causes of Klinefelter Syndrome 

Klinefelter syndrome is caused by the presence of extra X chromosomes in the cells of males. The anomaly occurs randomly. There can also be extra copies of genes on the X chromosome that disrupt development. There are no known causes for why the condition occurs.

Inheritance Pattern 

Is Klinefelter syndrome dominant or recessive? The genetic disorder is neither dominant nor recessive because Klinefelter syndrome is not inherited 1.

Instead it is a chromosome abnormality that occurs randomly at the time of conception.

It’s believed that half the time the error originates in the mother’s egg and the other half is due to the father’s sperm.

Can Klinefelter Syndrome Be Prevented? 

There is no way to prevent Klinefelter syndrome. Even if there were, because most cases aren’t diagnosed until later in life, preventative measures may not help.

Risk Factors for Klinefelter Syndrome 

Klinefelter syndrome affects males only so sex of a child is the biggest risk factor. 

There is evidence that indicates women who give birth over the age of 35 are slightly more likely to have a son with Klinefelter syndrome.

When a male with XXY uses infertility treatments to conceive, their child is at a higher risk of having the condition as well.

How Common Is Klinefelter Syndrome? 

Klinefelter syndrome is actually the most common chromosomal abnormality among males.

Medical professionals estimate that Klinefelter syndrome affects 150 in every 100,000 males but it could be as many as 1 in every 500 men. 

Cases where three or more X chromosomes are present are much less common, affecting just 1 in 50,000 newborn males.

Some research suggests that Klinefelter syndrome is becoming more common and may be more prevalent in some populations. More research on this is needed before a consensus can be established.

Diagnosis of Klinefelter Syndrome 

How is screening for Klinefelter's done? Is there a prenatal test for Klinefelter syndrome? Can Klinefelter Syndrome be detected before birth? These are all common questions parents have when there’s concern Klinefelter syndrome is a possibility.

Diagnosing Klinefelter syndrome based on symptoms alone can be difficult, and there is no standard guideline for clinical diagnosis. In some cases, the physical symptoms are so mild the condition isn’t diagnosed until puberty or early adulthood. 

Researchers have estimated that up to 75% of males with Klinefelter syndrome are never diagnosed 2,

and the vast majority that are receive a delayed diagnosis that doesn’t occur until puberty or later.

The only way to verify Klinefelter syndrome is with testing.

Prenatal Testing for Klinefelter Syndrome

Diagnosing Klinefelter syndrome in utero or at birth is rare. The only time it occurs is when one of two tests are done, usually for another reason. 

Chorionic Villus Sampling (CVS) - This test is done during pregnancy to identify possible chromosomal abnormalities. During the test, cells are taken from the chorionic villi in the placenta.

Amniocentesis - Amniocentesis testing involves a syringe being inserted into the placenta to extract a small amount of amniotic fluid that’s tested for chromosomal abnormalities.

Because these tests come with a small risk of miscarriage, their use is very conservative. Typically, they are only recommended when there is a high risk for another serious chromosomal problem. 

Genetic Testing for Klinefelter Syndrome

There are genetic tests that can diagnose Klinefelter syndrome. If the condition is suspected, then someone with medical genetics knowledge can order testing.

Most commonly, the physician will take a blood sample and send it off for chromosome analysis. The laboratory will generate a karyotype (picture of chromosomes) and look for the aneuploidy (too many or too few chromosomes).

Laboratory Testing for Klinefelter Syndrome 

In addition to genetic testing, hormone tests can also be used to measure various hormone levels, including testosterone. Individuals with Klinefelter Syndrome will have low levels of testosterone.

Treatment Options for Klinefelter Syndrome 

Klinefelter syndrome cannot be cured, but there are a variety of treatments to address the symptoms of Klinefelter syndrome. Klinefelter syndrome treatment costs can run into the thousands if surgery or repeated treatments are needed. 

Klinefelter syndrome is a condition that requires a multidisciplinary treatment approach involving one or more of the following specialists:

  1. Pediatricians

  2. Speech therapists

  3. General practitioners

  4. Psychologists and/or psychiatrists

  5. Infertility specialists

  6. Urologists

  7. Endocrinologists

Mild cases of Klinefelter syndrome may require no treatment. If treatment is needed, it’s recommended that they begin as early as possible, preferably during puberty or childhood.

Early intervention can prevent some symptoms from occurring. Klinefelter syndrome treatment with homeopathy is also prominent for treating secondary symptoms.

Breast Reduction Surgery

Breast reduction surgery can be used to remove excess breast tissue. It’s one of the most common types of cosmetic surgery for men.

The American Society of Plastic Surgeons’ 2018 Plastic Surgery Statistics notes that gynecomastia (breast reduction in men) increased 22% since 2000 with 24,753 procedures being performed in 2018.

As with any invasive surgery, there are risks involved with gynecomastia that should be discussed with a qualified surgeon.

Men who have enlarged breasts are at an increased risk of getting breast cancer. Men with this condition should be screened for cancer regularly.

Testosterone Replacement Therapy

This is one of the most common Klinefelter syndrome treatments since many of the symptoms stem from low testosterone. Individuals with this condition should see endocrinology to discuss testosterone therapy. 

It’s best to begin testosterone replacement therapy at the time of puberty so that boys develop as normally as possible.

The therapy will help with the development of hair growth, a deeper voice, increased muscle tone, bone strength and penis growth. 

Testosterone replacement therapy can be administered by injection, patch, pill or topical cream.

Patients who are using testosterone replacement therapy should work one-on-one with an endocrinologist.

Only 50% of males with Klinefelter syndrome have low testosterone so levels should be checked before starting treatments.

Infertility Treatment 

Assisted reproductive technology (ART) procedures can help some men with Klinefelter syndrome overcome infertility issues.

Approximately 50% of men with Klinefelter syndrome produce sperm but not in quantities large enough to fertilize an egg naturally. 

One of the most successful ART procedures is testicular sperm extraction with intracytoplasmic sperm injection. A fertility specialist will remove sperm from the testes and insert one sperm into an egg.

While ART procedures have improved in recent years, there’s still no guarantee they will work. The odds may be improved by freezing sperm in adolescence when the sperm is healthier.

Physical Therapy

Physical therapy is used to build strength and motor skills. The exact exercises used will vary.

Speech Therapy

If a child’s speech is impacted by Klinefelter syndrome therapy may be needed. Speech therapy should be started as soon as possible to maximize its effectiveness.

Occupational Therapy

Occupational therapy helps with functioning in social settings, work environments and school.

Behavioral Therapy

This type of therapy may be needed to build social skills and manage emotions.

Cognitive Therapy

Seeing a psychologist or psychiatrist can help alleviate emotional and mental problems associated with having Klinefelter syndrome. It’s commonly used to treat depression and anxiety.

The Prognosis for Klinefelter Syndrome 

The prognosis of Klinefelter syndrome depends on the extent of the condition. When treatments are done early, the severity of some related conditions is significantly reduced.

Analysis of 25 years of studies involving 466 men with Klinefelter syndrome found that patients had a 50% higher mortality rate 3 and their life expectancy was 5 years shorter than average. However, more recent research estimates that life expectancy is shortened by only 2 years 4.

Compared to many other chromosomal disorders, the prognosis of Klinefelter syndrome is generally good.

Klinefelter syndrome statistics show the health problems associated with the condition that can lead to death include:

  1. Cerebrovascular disease
  2. Breast cancer (comparable to female mortality rate)
  3. Respiratory diseases
  4. Subarachnoid hemorrhage
  5. Aortic valve disease

Can Klinefelter syndrome be cured? 

At this time there is no cure for Klinefelter syndrome because chromosomes cannot be removed from cells.

Living With Klinefelter Syndrome 

While life expectancy isn’t believed to be heavily impacted by Klinefelter syndrome, living with the condition can be difficult. Individuals with this condition might have lower self-esteem than their peers and need additional emotional support. 

Luckily, the treatment options noted above can greatly improve quality of life and prevent some complications from occurring.

Living with Klinefelter syndrome is much easier when intervention starts early.

Klinefelter's syndrome lifestyle effects are minimal for many men. They are able to lead normal lives that are fulfilling and well adjusted with few symptoms.

For others, it can be difficult to cope with the side effects, especially during adolescence. 

Klinefelter syndrome is classed as a disability when a child has learning disabilities.

Some XXY males will qualify for programs like the early intervention program for infants and toddlers with disabilities, which can have a huge impact on their education and social skills in the future 

Males with the condition may want to join a Klinefelter syndrome support group. There are also Klinefelter support groups for parents as well.

Talking with others who have the condition or a child with the condition can provide a sense of relief and understanding.

You can find Klinefelter syndrome support groups through your primary care physician.

Referenced Sources

  1. Klinefelter Syndrome Overview.
    Mayo Clinic Staff. October 4, 2016.
  2. Klinefelter syndrome.
    U.S. National Library of Medicine staff. April 2019.
  3. Causes of death in X chromatin positive males (Klinefelter's syndrome).
    W H Price, J F Clayton, J Wilson, S Collyer, R De Mey. December 1985.
  4. Klinefelter Syndrome—A Clinical Update.
    Kristian A. Groth, Anne Skakkebæk, Christian Høst, Claus Højbjerg Gravholt. January 1, 2013.