Klinefelter syndrome

Información en español Title

Not a rare disease

Other Names:

Klinefelter's syndrome; XXY syndrome; 47,XXY syndrome

Categories:

Congenital and Genetic Diseases

Summary Summary

Klinefelter syndrome (KS) is a condition that occurs in males when they have an extra X chromosome. Some males with KS have no obvious signs or symptoms while others may have varying degrees of cognitive, social, behavioral, and learning difficulties. Adults with Klinefelter syndrome may also have primary hypogonadism (decreased testosterone production), small and/or undescendent testes (cryptorchidism), enlarged breast tissue (gynecomastia), tall stature, and/or inability to have biological children (infertility), as well as an abnormal opening of the penis (hypospadias), and an small penis (micropenis). KS is not inherited, but usually occurs as a random event during the formation of reproductive cells (eggs and sperm) that results in the presence of one extra copy of the X chromosome in each cell (47,XXY). KS treatment is based on the signs and symptoms present in each person.^[1]^[2]^[3] Life expectancy is usually normal and many people with KS have normal life. There is a very small risk of developing breast cancer and other conditions such as a chronic inflammatory disease called systemic lupus erythematosus.^[3]

In some cases, there is more than one X chromosome in each cell (for example, 48,XXXY or 49,XXXXY). These conditions, which are often called "variants of Klinefelter" syndrome usually have more serious problems (intellectual disability, skeletal problems, and poor coordination) than classic Klinefelter syndrome (47,XXY).^[3]

Last updated: 2/14/2018

Symptoms Symptoms

The signs and symptoms of Klinefelter syndrome (KS) vary among affected people. Some men with KS have no symptoms of the condition or are only mildy affected. In these cases, they may not even know that they are affected by KS. When present, symptoms may include:^[1]^[2]^[3]

Small, firm testicles
Delayed or incomplete puberty with lack of secondary sexual characteristics resulting in sparse facial, body, or sexual hair a high-pitched voice and body fat distribution resulting in a rounder, lower half of the body, with more fat deposited in the hips, buttocks and thigh instead of around the chest and abdomen
Breast growth (gynecomastia)
Reduced facial and body hair
Infertility
Tall stature
Abnormal body proportions (long legs, short trunk, shoulder equal to hip size)
Learning disablity
Speech delay
Crypthochirdism
Opening (meatus) of the urethra (the tube that carries urine and sperm through the penis to the outside) on the underside of the penis (hypospadias) instead of the tip of the head of the penis
Social, psychologic and behavioral problems

Whether or not a male with KS has visible symptoms depends on many factors, including how much testosterone his body makes, if he is mosaic (with both XY and XXY cells), and his age when the condition is diagnosed and treated.^[1] Some people have a slightly increased risk of developing breast cancer, a rare extragonadal germ cell tumor, lung disease, varicose veins and osteoporosis as well as some autoimmune disorders such as systemic lupus erythematosus, rheumatoid arthritis and Sjogren's syndrome.^[2]^[4]

Some people with features of Klinefelter syndrome have more than one extra X chromosome in each cell (such as 48,XXXY or 49,XXXXY). In these cases, known as "variants of Klinefelter syndrome", the signs and symptoms can be more severe and may include:^[1]^[2]^[4]

Intellectual disability
Distinctive facial features
Skeletal abnormalities
Poor coordination
Severe speech difficulties
Behavioral problems
Heart defects
Teeth problems.

Last updated: 2/14/2018

Cause Cause

Klinefelter syndrome usually occurs as a random event during the formation of reproductive cells (eggs and sperm). An error in cell division called nondisjunction results in a reproductive cell with an abnormal number of chromosomes. For example, an egg or sperm cell may gain one or more extra copies of the X chromosome as a result of nondisjunction. If one of these atypical reproductive cells contributes to the genetic makeup of a child, the child will have one or more extra X chromosomes in each of the body's cells.^[2]

Most often, Klinefelter syndrome is caused by a single extra copy of the X chromosome, resulting in a total of 47 chromosomes per cell. Males normally have one X chromosome and one Y chromosome in each cell (46, XY), while females have two X chromosomes (46, XX). People with Klinefelter syndrome usually have two X chromosomes and one Y chromosome (47, XXY). Some people with Klinefelter syndrome have the extra X chromosome in only some of their cells; these people are said to have mosaic Klinefelter syndrome.^[2]

It is estimated that about half of the time, the cell division error occurs during development of the sperm, while the remainder are due to errors in egg development. Women who have pregnancies after age 35 have a slightly increased chance of having offspring with this syndrome.^[5]

The features of Klinefelter syndrome are due to the extra copies of genes on the extra X chromosome, which can alter male sexual development.^[3]

Some people with features of Klinefelter syndrome have conditions known as "variants of Klinefelter syndrome" where there is more than one extra sex chromosome in each cell (48,XXXY, 48,XXYY and 49,XXXXY).^[5]

Last updated: 2/14/2018

Inheritance Inheritance

Klinefelter syndrome is not inherited, but usually occurs as a random event during the formation of reproductive cells (eggs and sperm). An error in cell division called nondisjunction can result in reproductive cells with an abnormal number of chromosomes. For example, an egg or sperm cell may gain one or more extra copies of the X chromosome as a result of nondisjunction. If one of these reproductive cells contributes to the genetic makeup of a child, the child will have one or several extra X chromosomes in each of the body's cells.^[2]

Last updated: 2/14/2018

Diagnosis Diagnosis

A diagnosis of Klinefelter syndrome is often suspected based on the presence of characteristic signs and symptoms. Additional testing can then be ordered to confirm the diagnosis. This generally includes a chromosomal analysis (called a karyotype).^[3]^[6]

It is also possible to diagnosis Klinefelter syndrome before birth through chorionic villous sampling or amniocentesis.^[6]

Last updated: 2/14/2018

Treatment Treatment

Because symptoms of Klinefelter syndrome (KS) can sometimes be very mild, many people are never diagnosed or treated. When a diagnosis is made, treatment is based on the signs and symptoms present in each person, especially the problems related to hypogonadism, gynecomastia, and psychosocial problems. Treatment may include:^[1]^[3]^[4]

Testosterone replacement: About half of people with SK have low testosterone levels, which may be raised by taking supplemental testosterone. Having a more normal testosterone level can help affected people develop bigger muscles, a deeper voice, and facial and body hair, and may also increase sexual desire, enlarge the testes, improve mood, self-image, and behavior; it may also protect against osteoporosis and decrease the risks of autoimmune disease and breast cancer.
Breast removal or reduction surgery.
Educational interventions: As children, many people with Klinefelter syndrome qualify for special services to help them in school. Teachers can also help by using certain methods in the classroom, such as breaking bigger tasks into small steps.
Several forms of therapy such as physical, speech, occupational, behavioral, mental health, and family therapy can often help reduce or eliminate some of the symptoms of Klinefelter syndrome such as poor muscle tone; speech and language problems; or low self-confidence.

Last updated: 2/14/2018

Prognosis Prognosis

Babies with the 47, XXY form of Klinefelter differ little from healthy children. The results of one study on non-mosaic XXY infants younger than 2 years indicated that most XXY babies had normal external genitalia and facial features with height and weight in the normal range. Genetic testing had been performed due to a delay in walking and/or speech. Early diagnosis of Klinefelter syndrome is shown to be important to monitor potential developmental problems.^[4]

Boys with the 47, XXY karyotype may struggle through adolescence with academics, various frustrations, and, in a few instances, serious emotional or behavioral difficulties. However, most move toward full independence from their families as they enter adulthood. Some have completed graduate education and have a normal level of functioning. Lifespan is not affected by Klinefelter syndrome.^[4]

Last updated: 2/14/2018

Statistics Statistics

It is estimated that 1 in every 500 to 1,000 newborn males has an extra X chromosome, making Klinefelter syndrome one of the most common chromosomal disorders seen among newborns. Variants of Klinefelter syndrome (such as 48,XXXY, 49,XXXXY) are much rarer, occurring in 1 in 50,000 to 1 in 85,000 or fewer newborns.^[1]^[7]

It is suspected that Klinefelter syndrome is underdiagnosed because mild cases may not be identified. In addition, the features of this condition vary and can overlap significantly with those of other conditions.^[7]

Last updated: 10/13/2015

Do you have updated information on this disease? We want to hear from you.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

ClinicalTrials.gov lists trials that are related to Klinefelter syndrome. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.
The Research Portfolio Online Reporting Tool (RePORT) provides access to reports, data, and analyses of research activities at the National Institutes of Health (NIH), including information on NIH expenditures and the results of NIH-supported research. Although these projects may not conduct studies on humans, you may want to contact the investigators to learn more. To search for studies, enter the disease name in the "Text Search" box. Then click "Submit Query".

General Clinical Trials & Research

The Eunice Kennedy Shriver National Institute of Child Health and Human Development provides information about research activities and scientific advances relating to Klinefelter syndrome.

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Association for X and Y Chromosome Variations (AXYS)
P.O. Box 861
Mendenhall, PA 19357
Toll-free: 888-999-9428
E-mail: info@genetic.org
Website: http://www.genetic.org

Do you know of an organization? We want to hear from you.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Education Resources

The Genetics Education Materials for School Success (GEMSS) aims to assure that all children with genetic health conditions succeed in school-life. Their Web site offers general and condition-specific education resources to help teachers and parents better understand the needs of students who have genetic conditions.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) provides information related to the health of children, adults, and families. Click on the link to view information on this topic.
Genetics Home Reference (GHR) contains information on Klinefelter syndrome. This website is maintained by the National Library of Medicine.
MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
The National Human Genome Research Institute's (NHGRI) website has an information page on this topic. NHGRI is part of the National Institutes of Health and supports research on the structure and function of the human genome and its role in health and disease.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
MeSH® (Medical Subject Headings) is a terminology tool used by the National Library of Medicine. Click on the link to view information on this topic.
The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Klinefelter syndrome. Click on the link to view a sample search on this topic.

News & Events News & Events

News

Developing a New Tool to Detect a Frequently Missed Sex Chromosome Disorder in Boys
August 25, 2015

Related Diseases Related Diseases

The following diseases are related to Klinefelter syndrome. If you have a question about any of these diseases, you can contact GARD.

47, XXY

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

I have recently been diagnosed with mosaic Klinefelter syndrome and I am trying to find out what the frequency is. See answer
I have Klinefelter syndrome and I was wondering if weight gain is a common problem. Are there studies with ideas of how I could lose the extra weight. See answer
My son is 15 years old and he was diagnosed with KS almost 2 years ago. He is starting to have some emotional problems. He also struggles with suicidal thoughts. Is this normal for someone his age with KS and also should he be taking a hormone replacement at his age? See answer
How many people tend to get this disease? See answer
My husband has Klinefelter syndrome and we were hoping to go through the ICSI/IVF treatment but we wanted to know if we were successful with the pregnancy with a boy would the boy baby also have Klinefelter syndrome because the father has it? See answer
If a woman has a 47, XXY karyotype, does this mean that she has Klinefelter syndrome? See answer
We have just been told that our 2.5 year old grandson has Klinefelter syndrome. We know very little about this condition and how it will affect him and his family in the future. Where can we find additional information? How can we find a health professional to discuss this in more detail? See answer
My son has Klinefelter syndrome. I am aware that he may need testosterone replacement therapy (TRT) when he reaches puberty. For how long is TRT usually done? See answer
Klinefelter syndrome can be caused by nondisjunction. What increases the risk of males or females to have nondisjunction during meiosis? What research is currently underway for Klinefelter syndrome? See answer
My husband has Klinefelter syndrome. I have read a lot of things about this syndrome, but I want to know more about the future. He is 33-years-old, and he didn't take any medication for Klinefelter syndrome in the past. What is the chance of him becoming a father? See answer

Have a question? Contact a GARD Information Specialist.

References References

Klinefelter syndrome. Eunice Kennedy Shriver National Institute of Child Health and Human Development. November 2013; http://www.nichd.nih.gov/health/topics/klinefelter/Pages/default.aspx.
Klinefelter syndrome. Genetics Home Reference. January 2013; http://ghr.nlm.nih.gov/condition=klinefeltersyndrome.
Kirmse B. Klinefelter syndrome. MedlinePlus. November 2014; http://www.nlm.nih.gov/medlineplus/ency/article/000382.htm.
Chen H. Klinefelter syndrome. Medscape Reference. July 2015; http://emedicine.medscape.com/article/945649-overview.
Learning about Klinefelter syndrome. National Human Genome Research Institute. October 2011; http://www.genome.gov/19519068.
Klinefelter Syndrome. National Organization for Rare Disorders. 2014; http://rarediseases.org/rare-diseases/klinefelter-syndrome/.
Klinefelter syndrome. Genetics Home Reference (GHR). January 2013; http://ghr.nlm.nih.gov/condition/klinefelter-syndrome. Accessed 4/14/2015.