A typical male has a total of 46 chromosomes (packages of DNA) – one copy of an X chromosome and one copy of the Y chromosome (46, XY). A typical girl has two copies of the X chromosome (46, XX). There are a number of different conditions where an individual may have more or less than the expected X or Y chromosomes. Klinefelter syndrome (KS) is a genetic condition where there’s an extra X chromosome present in a male’s genetic code. Instead of having a total of 46 chromosomes, they have 47 — with two copies of the X chromosome and one copy of the Y chromosome (47, XXY). There are some forms (called mosaic) where only some (not all) of the person’s cells have this change (other cells can either have the typical 46 XY, or can have another abnormality).
Klinefelter syndrome is a congenital condition, which means it’s present from the time of birth. There are certain tests that can be done during the mother’s pregnancy that can diagnose it before birth, however more often it’s diagnosed later in life. If not found before birth, it can sometimes be diagnosed because the baby has a smaller penis than expected, or later in the teenage years if puberty doesn’t start or progress as expected. Many males may not be diagnosed at all, or only when experiencing fertility challenges later in life (if they’re having a difficult time getting pregnant with their partner).
In most cases, the differences in their puberty and/or fertility are because the testicles have early “failure” and cannot make enough testosterone and/or sperm. This results in these individuals needing testosterone replacement and testing for fertility.
People with Klinefelter syndrome are also more likely to develop certain conditions that are part what is known as metabolic syndrome. These conditions include:
. Hypertension (high blood pressure).
. Type 2 diabetes.
. High cholesterol and fats called triglycerides in the blood.
Males with Klinefelter syndrome are also more likely to develop:
. Gynecomastia (breast growth in a male).
. Breast cancer.
. Osteoporosis (weakened bones).
. Autoimmune diseases (including type 1 diabetes, thyroid disease, lupus and rheumatoid arthritis).
. Seizure disorders.
. Learning differences (especially language skills).
This condition can be managed by treating the symptoms — often including hormone replacement, physical therapy and behavioral therapy.
Klinefelter syndrome is fairly common, happening in about 1 in 600 males, but many men (some say 70 to 80%) likely do not know they have this condition.
Typically, a person’s genetic code is made up of either two X chromosomes (genetic female) or one X and one Y chromosome (genetic male). At conception, the mother has one chromosome in an egg and the father has one in the sperm. The egg holds an X. The sperm could have either an X or a Y chromosome. In a typical situation, if an X sperm meets an egg holding an X, the resulting baby will be a female (46, XX). If the sperm holds a Y chromosome when it meets the egg, the resulting baby will be a male (46, XY).
Klinefelter syndrome happens when there is an extra X chromosome in the genetic code. This change happens before birth and can happen in a few different ways. These ways include:
. A sperm cell carries an extra X chromosome.
. An egg cell holds an extra X chromosome.
. Cells divide incorrectly early in the development process of a fetus (called mosaic Klinefelter syndrome).
There are other rare differences in genetic code where there can be other combinations of X and Y chromosomes that are more generally referred to as “X and Y variations/syndromes.” These conditions may overlap with Klinefelter syndrome, but also may have different, and in some cases more severe, features.
The symptoms of Klinefelter syndrome can vary in severity. Some people may have quite a few symptoms, while others might not have any that are obvious. There are two general types of symptoms — physical and intellectual. Physical symptoms are those that impact the body. Intellectual symptoms aren’t something you can see, but instead include things like behavioral issues and learning disabilities.
Physical symptoms of Klinefelter syndrome include:
. Being born with a smaller penis, and/or undescended testicle(s).
. Having abnormal body proportions. (This can include being too tall, having long legs and a short trunk and the shoulders being equal to hips in size rather than wider, which is more typical in a male.)
. Having flat feet or an unusual fusion of certain bones in the forearms.
. Having difficulty with “gross motor” function (coordination).
. Having testicular failure (not making enough testosterone or sperm).
. Experiencing increased breast tissue (gynecomastia) in teen or adult years.
. Having an increased risk for blood clots.
. Having weaker bones or more fractures (called either osteopenia or osteoporosis as an adult).
People with Klinefelter syndrome often experience infertility. Whenever possible, these patients should be seen by a fertility specialist at the time of diagnosis (preferably before starting testosterone) for discussion of possible fertility preservation methods (or to confirm that this is not possible).
Intellectual symptoms of Klinefelter syndrome can include:
. Experiencing depression and anxiety.
. Having social and behavioral issues.
. Displaying impulsive behaviors and having emotional immaturity.
. Experiencing learning disabilities (reading and language differences are common).
. Having attention-deficit/hyperactivity disorder (ADHD).
. Having speech delay.
. Having autism spectrum disorder.
Klinefelter syndrome is typically diagnosed in one of the following ways:
. Prenatal screening.
. Testing after a healthcare provider notices abnormal growth during childhood, puberty or throughout the teen years.
. Testing for fertility issues and/or low testosterone in adulthood.
The doctor will look at the chromosomes to check for an extra X chromosome. Looking at someone’s chromosomes is done by a blood test called karyotype. This test can confirm a diagnosis of Klinefelter syndrome because there are 47 chromosomes, including two X chromosomes and a Y. This can be done in children, adults and even in a baby before birth.
It isn’t standard to test babies for Klinefelter syndrome before birth, but if certain tests are done that gather genetic material from tissue or fluid (chorionic villus sampling or amniocentesis) it can be detected. Chorionic villus sampling involves taking a sample from the placenta (the food source for the baby in the uterus). Amniocentesis involves taking a sample from the amniotic fluid that the baby is in within the womb. Both of these sample sites have genetic material from the baby and can help the healthcare provider determine if Klinefelter syndrome is present. There are also new types of non-invasive prenatal testing (NIPT) designed to look for other extra chromosomes. However, it’s unclear how accurate these non-invasive tests are in diagnosing Klinefelter syndrome.
In people with very mild cases of Klinefelter syndrome — those without symptoms — the condition may never be diagnosed or treated. Some people believe that only 20 to 30% of all people with Klinefelter syndrome ever know about their diagnosis. For others, it’s only discovered when the man is tested for infertility.
Unfortunately, Klinefelter syndrome is a genetic condition that cannot be prevented. It’s a random error in the genetic code that happens before birth. This condition is not passed down through a family (inherited) and there is nothing a parent can do to prevent their child from having Klinefelter syndrome.
Klinefelter syndrome is a condition that’s present from birth (congenital). Because it’s a part of a person’s genetic code, this condition cannot be cured or completely gotten rid of. However, the symptoms of Klinefelter syndrome can be managed over time to cut down on their impact on a person’s life.
Some treatments for the symptoms of Klinefelter syndrome can include:
. Hormone replacement.
People with Klinefelter syndrome often have less of the hormone testosterone than typical males. Some boys will not start puberty changes at all, whereas others will start but then stop or regress. This happens because the testicles usually “fail” in Klinefelter syndrome, which makes them unable to make testosterone and sperm. Replacing the testosterone hormone can help minimize some of the symptoms of the condition. In children and teens testosterone is usually replaced via injection. In older men, other treatment options can include gels.
When the level of testosterone in the body goes up with treatment, the person with Klinefelter syndrome may have:
. An increased sexual desire.
. More body and facial hair.
. A deeper voice.
. Stronger muscles.
This type of treatment can also help improve a person’s mental state, including their self-image and mood. It should be noted that if diagnosed at or before teen years, a fertility evaluation should be done — ideally before starting testosterone — to see if there is any sperm that can be collected. Since most men with Klinefelter syndrome eventually lose the ability to make sperm, it’s most common that men with Klinefelter are considered infertile. Unfortunately, treating these men with testosterone doesn’t help.
Those with Klinefelter syndrome may need help from a number of different therapists, including:
. Speech and language therapists.
. Physical and/or occupational therapists.
. Emotional, behavioral and family therapists.
Therapy can really help limit the impact of certain symptoms of Klinefelter syndrome. For example, physical therapy can help with muscle tone, while a speech and language therapist may be able to address speech issues. Behavioral and family therapy have both been shown to help people with Klinefelter syndrome and can help manage depression and/or anxiety, which are common.
Children with Klinefelter syndrome may also need changes in the classroom to help them learn. Many children with this condition will qualify for special help in school to adapt the lessons in a way that works for them. It’s recommended that children be tested. It is also recommended that children with Klinefelter get neuropsychological testing when they are diagnosed and every few years to help identify learning challenges and to guide the schools as to how to best help their learning.
Extra breast tissue can be a normal finding in all teenage boys (occurring in approximately half), but it usually goes away on its own. However, in Klinefelter syndrome the extra breast tissue is more likely to stay. In some cases — mostly if it’s very bothersome to the person — the healthcare provider may decide to surgically remove extra breast tissue. This removal or reduction surgery can help the individual with self-image and confidence, but is usually delayed until adult age.
Klinefelter syndrome can vary widely in severity. People with a mild case may not even know they have Klinefelter syndrome. Some men with mild cases only discover that they have Klinefelter syndrome during infertility testing.
The use of genetic testing before birth is increasingly being used and sometimes can diagnose Klinefelter syndrome. For babies and young children with Klinefelter syndrome, there is generally little difference compared to other boys — although sometimes a smaller penis and/or undescended testicle(s) may be noted. Behavioral, motor and learning issues may also be noted in childhood, but if diagnosis of Klinefelter is not known, this can be thought to be due to other things.
The benefit of knowing the diagnosis earlier in life lets the healthcare provider not only to help educate and prepare the family for what to expect, but also to screen for the issues that children with Klinefelter syndrome are more likely to have. For many, Klinefelter syndrome can be positively managed and a normal life is possible.