Klinefelter syndrome

Title

Not a rare disease

Other Names:

Klinefelter's syndrome; 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 experience primary hypogonadism (decreased testosterone production), small testes, enlarged breast tissue (gynecomastia), tall stature, and/or infertility. KS is not inherited, but usually occurs as a random event during the formation of reproductive cells (eggs and sperm). Treatment is based on the signs and symptoms present in each person.^[1]^[2]^[3]

Last updated: 10/13/2015

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:^[2]^[3]^[1]

Small, firm testicles
Delayed or incomplete puberty
Breast growth (gynecomastia)
Reduced facial and body hair
Infertility
Tall height
Abnormal body proportions (long legs, short trunk, shoulder equal to hip size)
Learning disablity
Speech delay

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]

Last updated: 10/12/2015

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.^[4]

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]

Last updated: 10/12/2015

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: 10/12/2015

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).^[5]^[3]

It is also possible to diagnosis Klinefelter syndrome before birth through chorionic villous sampling or amniocentesis.^[5]

Last updated: 10/12/2015

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. This may include:^[1]^[3]^[6]

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.
Therapeutic options - A variety of therapists, such as physical, speech, occupational, behavioral, mental health, and family therapists 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.
Medical management - About half of people with KS 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. Many healthcare providers recommend testosterone therapy when a boy reaches puberty. However, not all males with KS benefit from testosterone therapy. Some affected people may opt to have breast removal or reduction surgery.

The Eunice Kennedy Shriver National Institute of Child Health and Human Development's Web site offers more specific information on the treatment and management of Klinefelter syndrome. Please click on the link to access this resource.

Last updated: 10/13/2015

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 detection of Klinefelter syndrome is shown to be important to monitor potential developmental problems.^[6]

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.^[6]

Last updated: 10/13/2015

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.^[7]^[1]

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

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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 studying or have studied 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".

Organizations Organizations

Nonprofit support and advocacy groups bring together patients, families, medical professionals, and researchers. These groups often raise awareness, provide support, and develop patient-centered information. Many are the driving force behind research for better treatments and possible cures. They can direct people to research, resources, and services. Many groups also have experts who serve as medical advisors. Visit their 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

American Association for Klinefelter Syndrome Information and Support
3796 Odgen Lane.
Mundelein, IL 60060-6038
Toll-free: 888-466-5747
E-mail: KSinfo@aaksis.org
Website: http://www.aaksis.org
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? Send us your suggestions.

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

NCATS Co-Sponsored Conferences

XXY/Klinefelter Syndrome in 2000: Expanding the Phenotype and Identifying New Research Directions Thursday, August 31, 2000 - Wednesday, August 30, 2000
Location: NIH Campus, Bethesda, MD
Description: The clinical and research objectives of this conference were to summarize current knowledge concerning the incidence of Klinefelter syndrome and its genetic (cytologic) basis, clarifying the role X-inactivation plays in the widely varied phenotype; summarize the spectrum of clinical features in XXY Klinefelter syndrome—reproductive dysfunction, structural anomalies, and neurologic/cognitive/behavioral dysfunction; review current treatment and management of hormonal deficiency, infertility, and neurologic/behavioral perturbation; summarize current beliefs concerning the biologic basis of functional defects; and delineate those new research areas that would benefit from more focused attention.

Contact: Dr. Felix de la Cruz(301) 496-1383

Co-funding Institute(s): National Institute of Child Health and Human Development

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 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.
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/.
Chen H.. Klinefelter syndrome. Medscape Reference. July 2015; http://emedicine.medscape.com/article/945649-overview.
Klinefelter syndrome. Genetics Home Reference (GHR). January 2013; http://ghr.nlm.nih.gov/condition/klinefelter-syndrome. Accessed 4/14/2015.