Understanding Klinefelter Syndrome
In recognition of Eunice Kennedy Shriver, whose boundless vision advanced the progress of people with disabilities for generations, in appreciation for her special interest in this project and the generous contribution of the Joseph P. Kennedy, Jr. Foundation toward the funding and support of this booklet.

Overview of Klinefelter Syndrome, 47,XXY

This booklet offers information for expectant parents first learning about Klinefelter syndrome or 47,XXY, which is a chromosome condition. Chromosomes are tiny, but very important, structures in every cell. Chromosomes carry all of our genes, and genes give instructions for our bodies to grow and function. Most people are born with 46 chromosomes in their cells: 23 from their mother and 23 from their father. Males are usually born with an X and a Y chromosome. XXY occurs when a male has an extra X chromosome in some or all cells of his body. About 1 out of every 660 males is born with XXY, and there about 300,000 with this condition in the U.S. (Aksglaede et al., 2013; Bojeson et al, 2003). The genes on the extra X chromosome can impact growth and development.

Features

Like most people, individuals with XXY have strengths and challenges that no one can predict before birth. The outcomes can also vary widely. Sometimes the features of XXY can be so mild that a diagnosis is not made until puberty or adulthood. Researchers believe that up to 75 percent of men with XXY may never be diagnosed (Nieschlag, 2013). Males with XXY can have certain physical features, psychological or health issues, or learning disabilities. Most males with XXY have some but not all of the symptoms. Further, almost all men with XXY have low testosterone (the male sex hormone). Men with XXY typically cannot conceive children naturally due to low numbers of sperm. However, fertility treatment options may be pursued.

Subtle physical features might include a curved little finger and less facial or body hair. Many men with XXY tend to be slightly taller than average. In addition, they may have longer arms and legs and often have small testes as adults.

Childhood

Most men with XXY are of average intelligence. However, boys with XXY may have short attention spans or learning disabilities. They may also have some speech-language or behavior issues. If a boy with XXY has any of those conditions, he might need extra support from school staff and other specialists (Aksglaede, 2013). If a boy with XXY has issues with social skills or behavior, professional counseling and therapies might also be helpful.

Adolescence and Adulthood

Recent advances have also helped teens and men with XXY to thrive. Hormone treatments have helped most to complete puberty and maintain hormone levels for good health. Options for planning a family also continue to be an active area of research and treatment. Individuals with XXY can also stay healthy with good medical, dental, and mental health care, like anyone else. Most adults with XXY live independently and can be found working in many different careers.

More information about XXY can be obtained from The Association for X and Y Chromosome Variations (AXYS) and its local chapters, as well as XXY clinics nationwide. Some people prefer to call the condition XXY, and others prefer Klinefelter syndrome or KS. Because the men with this condition we interviewed have said they prefer XXY, we will use that term in this booklet.

References:
Aksglaede, L., Link, K., Giwercman, A., Jørgensen, N., Skakkebæk, N. E., & Juul, A. (2013, February). 47, XXY Klinefelter syndrome: Clinical characteristics and age-specific recommendations for medical management. In American Journal of Medical Genetics Part C: Seminars in Medical Genetics (Vol. 163, No. 1, pp. 55-63). Hoboken: Wiley Subscription Services, Inc., A Wiley Company.
Bojesen A, Juul S, Gravholt CH 2003 Prenatal and postnatal prevalence of Klinefelter syndrome: a national registry study. J Clin Endocrinol Metab 88:622-626
Nieschlag, E. (2013). Klinefelter syndrome: the commonest form of hypogonadism, but often overlooked or untreated. Deutsches Ärzteblatt International, 110(20), 347.

XXY Syndrome Diagnosis

XXY may be diagnosed through prenatal testing during pregnancy or after a baby is born. This condition occurs randomly. XXY is not caused by anything the parents did or did not do during or before pregnancy. Health professionals involved in testing for XXY and explaining the condition might include obstetricians, pediatricians, and primary care physicians. Other specialists involved might also include maternal-fetal medicine doctors, medical geneticists, genetic counselors, and endocrinologists (hormone specialists).

Prenatal Screening and Testing Options

A blood test, called cell-free DNA (cfDNA) screening or non-invasive prenatal screening tests (NIPS), may show if there is an increased chance for XXY or other chromosome conditions. However, these screening tests are not 100% certain. There can be false positives with this screening test (Palomacki, 2018; Davis et al., 2016). A false positive is when someone receives a positive screening result even when the baby does not have the condition. More testing is needed if expectant parents want to know for sure to make decisions about care. Only chorionic villus sampling (CVS) or amniocentesis, which are tests that look directly at the chromosomes, are nearly 100% accurate in confirming a prenatal diagnosis for XXY. These tests do involve a very small risk of miscarriage, shown to be less than 1% (ACOG, 2016).

Prenatal Testing Considerations.

Before or after prenatal testing, expectant parents can talk to their medical providers about how they plan to use the information. Some might use prenatal test results to prepare or make specific delivery plans. However, the birth of a baby with XXY is often fairly standard. Some expectant parents might use the time during pregnancy to find helpful resources about the condition. Others may use a confirmed prenatal diagnosis to make decisions about pregnancy management or to think about adoption. Some expectant parents may also use a prenatal diagnosis to plan next steps. They might want to meet with specialists to discuss possible hormone treatments in the future. They might also learn about supports and services. For all of these personal decisions, obstetric and genetic health professionals can give more information and referrals to specialists as needed.

Diagnosis Discussions

XXY is diagnosed through one of two tests, a karyotype (picture of the chromosomes) or microarray (chromosome map). Health professionals, such as genetic counselors, geneticists, obstetricians, and maternal-fetal medicine doctors, can explain the genetic test results and provide details about what the diagnosis means. They can also give parents important resources and information about XXY.

Local genetic counselors and medical geneticists can be found by asking a physician for a local referral or by searching online at the National Society of Genetic Counselors (nsgc.org) or the American College of Medical Genetics and Genomics (acmg.net).

References:
Palomaki, G. E., Messerlian, G. M., & Halliday, J. V. (2018). Prenatal screening for common aneuploidies using cell-free DNA. UpToDate, Waltham, MA. Accessed April, 4.
ACOG Practice Bulletin No. 640. (2015). Cell-free DNA screening for aneuploidy. Obstet Gyneco, 126:e31-37.
Davis, S., Howell, S., Wilson, R., Tanda, T., Ross, J., Zeitler, P., & Tartaglia, N. (2016). Advances in the interdisciplinary care of children with Klinefelter syndrome. Advances in Pediatrics, 63(1), 15.

Medical Issues

After Birth:

Most babies with XXY do not have major health problems. The birth is often not any different than the birth of a baby without XXY. A thorough physical exam by a doctor who is familiar with XXY can help identify issues of concern. Infants with XXY might have low muscle tone (also called hypotonia). Hypotonia can cause developmental delays, which can often be helped with physical therapy. Infant boys with XXY may also have a small penis, or micropenis. The condition can be treated with a series of three testosterone shots (Groth et al., 2013). Further, some babies with XXY may have an undescended testicle or a hernia, which might need treatment (Davis et al., 2016). Babies who have any issues with their genitals should be referred to a urologist for treatment. Babies with XXY may also have a small increased risk for cleft palate, which can be evaluated at birth.

During Childhood and Beyond:

Boys with XXY also have higher chances for some health conditions. Regular dental care and healthy eating can help prevent problems such as tooth decay. Annual exams and hormone therapy by an endocrinologist familiar with XXY is an important way to treat and prevent many of these medical issues like osteoporosis (thinning and weaker bones). Annual exams and hormone therapy by an endocrinologist familiar with XXY is an important way to treat and prevent many of these medical issues. Therefore, all boys with XXY need to be referred to a pediatric endocrinologist during early puberty to learn more about their options.

Almost half of adults with XXY also have metabolic syndrome, a condition which increases the risk of developing type 2 diabetes, fatty liver, high blood pressure, and high cholesterol. Adults with XXY also have higher chances for heart disease and blood clots. Most of these conditions can be treated with medication, healthy habits, and regular medical care. Boys and men with XXY are usually able to maintain a healthy, active lifestyle with exercise and good nutrition, like most other people. Most healthy men with XXY can live long lives. Parents can find more information about XXY health issues by contacting the nearest specialty clinic. (Davis, 2016)

For more information, please see the following:
Healthy Children: Klinefelter Syndrome: A Guide for Families
Genetic Home Reference: Klinefelter Syndrome
Klinefelter Syndrome Clinic Directory » genetic.org/clinics
47,XXY Klinefelter syndrome: Clinical characteristics and age-specific recommendations for medical management

References:
Groth, K. A., Skakkebæk, A., Høst, C., Gravholt, C. H., & Bojesen, A. (2013). Klinefelter syndrome—a clinical update. The Journal of Clinical Endocrinology & Metabolism, 98(1), 20-30.
Davis, S., Howell, S., Wilson, R., Tanda, T., Ross, J., Zeitler, P., & Tartaglia, N. (2016). Advances in the interdisciplinary care of children with Klinefelter syndrome. Advances in Pediatrics, 63(1), 15.

Growth and Development

Many males with XXY syndrome tend to be tall and may have slightly longer arms and legs. They may begin to grow faster than their peers at around 5 years of age (Aksglaede, 2013). Boys with XXY typically start puberty on time and have normal male sexual development. However, their testicles as adults are usually smaller than average. During adolescence, their testicles do not continue to make enough testosterone (male sex hormone). This condition is called hypogonadism. The lower levels of testosterone can cause a man with XXY to have less facial and body hair. Some young men with XXY also develop breast tissue (gynecomastia) starting during puberty. (Davis, 2016).

Experts recommend visiting an endocrinologist (a hormone specialist) when a boy with XXY is around 10 years of age or at the first sign of puberty, whichever comes first. Endocrinologists can explain the changes during puberty and can discuss options for testosterone supplements. This hormone supplement can help boys with XXY progress through puberty and maintain healthy bones and muscles. Sometimes men with XXY have less interest in sex, and hormone treatment can also help increase their desire (Davis, 2016).

Almost all grown men with XXY have fertility issues because of the lack of sperm in their semen. Fortunately, men with XXY still have many options to father children. Almost half of men with XXY can have a biological child using assisted reproductive technology (ART) (Davis et al., 2016). In these cases, urologists (urinary tract doctors) use surgery to retrieve sperm from the testicles of individuals with XXY. The sperm can later be injected into an egg for pregnancy. Other men with XXY may choose to start a family through adoption or use of donor sperm (Groth, 2013).

References:
Aksglaede, L., Link, K., Giwercman, A., Jørgensen, N., Skakkebæk, N. E., & Juul, A. (2013, February). 47, XXY Klinefelter syndrome: Clinical characteristics and age-specific recommendations for medical management. In American Journal of Medical Genetics Part C: Seminars in Medical Genetics (Vol. 163, No. 1, pp. 55-63). Hoboken: Wiley Subscription Services, Inc., A Wiley Company.
Groth, K. A., Skakkebæk, A., Høst, C., Gravholt, C. H., & Bojesen, A. (2013). Klinefelter syndrome—a clinical update. The Journal of Clinical Endocrinology & Metabolism, 98(1), 20-30.
Davis, S., Howell, S., Wilson, R., Tanda, T., Ross, J., Zeitler, P., & Tartaglia, N. (2016). Advances in the interdisciplinary care of children with Klinefelter syndrome. Advances in Pediatrics, 63(1), 15.

Healthcare and Developmental Services

Boys with XXY syndrome may need extra medical care. Therefore, insurance coverage under regular group health plans or state programs, such as Medicaid or the Children’s Health Insurance Program (CHIP), is very important. Good medical and dental care can help prevent some of the adult medical conditions that can occur in men with XXY, such as diabetes, metabolic syndrome, blood clots, and dental issues.

Early Intervention, a program found in all states, can evaluate children from birth to age three for any delays. EI can also provide therapies as needed. These services are usually provided at no cost or for a “sliding-scale” fee. Therapists can work with families in their homes to help children meet developmental milestones, like learning to walk or speak if the child is delayed. Nearly all boys with XXY reach these milestones, but some may be delayed and need extra help.

Boys with XXY may have a range of mild to moderate developmental delays. Studies show that 75% of boys with XXY have mild speech-language delays, and 50% have motor delays for skills like walking. Boys with XXY often need Early Intervention or private therapies to achieve those milestones. However, between 25% and 50% of boys with XXY meet those milestones without extra help (Davis, 2016).

For more information, please also refer to the following resources:
Center for Parent Information and Resources (CPIR) » parentcenterhub.org

Resources:
Davis, S., Howell, S., Wilson, R., Tanda, T., Ross, J., Zeitler, P., & Tartaglia, N. (2016). Advances in the interdisciplinary care of children with Klinefelter syndrome. Advances in Pediatrics, 63(1), 15.

Education and Behavior Support

Most men and boys with XXY syndrome are of average intelligence (IQ) and graduate high school. Many attend college or trade schools. Some may need extra support to successfully complete these programs or maintain jobs later on. Most live independently and can enjoy meaningful jobs. However, boys with XXY syndrome also have higher chances for learning disabilities, such as dyslexia and challenges with verbal and language-based learning (Boada, 2011). Therefore, boys with XXY syndrome may benefit from ongoing developmental and academic assessments starting in early childhood. These assessments can determine if students need extra help in some areas such as speech, reading, or attention. If any issues need to be addressed, boys with XXY can be treated with different kinds of proven therapies. They may also benefit from special education supports and services in school. About 80% of boys with XXY need extra support at school with language and reading.

Boys with XXY also have higher chances for attention deficit hyperactivity disorder (ADHD). This often means they have a hard time paying attention even though they usually are not hyperactive. While ADHD has no impact on their intellectual ability, school supports may help their learning in the classroom. Studies show that some boys with XXY and ADHD respond well to the medication and treatment often used for ADHD (Davis, 2016). Individuals with XXY may also have Auditory Processing Disorder (APD) and receive treatment if needed. APD is an issue with how the brain interprets sounds and speech; it can be diagnosed by an audiologist (hearing specialist). Boys with XXY also have higher chances for mild autism spectrum disorders (ASD), depression, emotional immaturity, and anxiety. Families, doctors, and schools can watch for the signs. They can make sure boys with XXY get the assessments and supports they may need. For example, speech-language therapy and social skills groups at school can help boys who may need help with speech or social skills. Further, behavioral counseling and/or medication can help boys deal with depression or anxiety. Boys with XXY often need to receive multi-specialist evaluations and recommendations to make sure they are getting full support.

As with any child, experts recommend helping boys with XXY to find their strengths and talents to build positive self-esteem (Turriff, 2015). They can also build a positive self-image through friendships, clubs and activities, and interests that they enjoy. Yet, boys with XXY may need extra support in areas. For example, some tend to be shy and need more help with social cues. In addition, boys with XXY who have coordination and muscle issues may feel frustration with team sports (Visootsak and Graham, 2008). Therefore, some may value more individual activities (such as playing music instruments, tennis, fencing, martial arts, etc.). While these are points to consider, a boy with XXY should be supported in pursuing whatever interests him the most.

For more information about non-verbal learning disabilities, see the following:
Understood » understood.org
Pediatric Evaluation and Treatment Recommendations for XXY/Klinefelter syndrome

References:
Davis, S., Howell, S., Wilson, R., Tanda, T., Ross, J., Zeitler, P., & Tartaglia, N. (2016). Advances in the interdisciplinary care of children with Klinefelter syndrome. Advances in Pediatrics, 63(1), 15.
Turriff, A., Levy, H. P., & Biesecker, B. (2015). Factors associated with adaptation to Klinefelter syndrome: The experience of adolescents and adults. Patient Education and Counseling, 98(1), 90-95.
Boada, R., Janusz, J., Hutaff‐Lee, C., & Tartaglia, N. (2009). The cognitive phenotype in Klinefelter syndrome: a review of the literature including genetic and hormonal factors. Developmental disabilities research reviews, 15(4), 284-294.
Visootsak, J., & Graham Jr, J. M. (2009). Social function in multiple X and Y chromosome disorders: XXY, XYY, XXYY, XXXY. Developmental disabilities research reviews, 15(4), 328-332.

Families

Families are an important source of nurturing, support, and strength for a boy with XXY. This is true for any child. Parents can help their son understand his diagnosis by talking about growth, puberty, and fertility issues as he becomes ready.

Parents often worry about how and when to approach these discussions with their son. These are not one-time discussions. These talks involve providing information over time. For example, parents may want to talk to their son about his diagnosis if he is going to therapies or medical visits. Parents need to present this information based on what is most important for their son to know at the time. They also need to use language their son can understand at his age and developmental level. Information should be explained in a way that builds trust and positive support between parents and their child.

Parents may seek guidance from professional supports, such as physicians or genetic counselors. These professionals can help parents address their own emotions about the diagnosis. They can also help parents prepare, inform, and better understand their son and any possible challenges. This guidance can help parents look out for any concerns their son might have about body image or bullying. Then families can seek support for their son on how to manage teasing or bullying if it should happen. When given the proper support, men with XXY report that their condition has given them increased empathy for others and a broader worldview (Turriff, 2016).

Some boys with XXY are often shy and may have a hard time understanding social cues (like how to join a conversation). Therefore, parents may need to get extra help for them to develop and grow their social skills. Getting boys involved with clubs and activities among peers can also help them make friends and develop their talents. With support as needed, men and boys with XXY can make friends and enjoy meaningful relationships just like anyone else (Davis, 2016).

Families may also need to reframe outdated perspectives about XXY. Early research on XXY was performed only on people in prison even though XXY is a common condition among all men. Some of the early studies claimed that men with XXY have higher chances for becoming criminals. However, this has been proven untrue and was biased based on the study setting. This is a false stereotype that parents might need to address at times (Davis, 2016).

Parents also need to help their son plan for an independent future, recognizing his individual strengths and weaknesses. Parents can take steps toward developing his skills, just as they would do for any of their children. Men with XXY have built successful careers in many different fields.

For more stories from parents and individuals with XXY, please see the following:
Living with Klinefelter Syndrome, Trisomy X (47,XXX) and 47,XYY: A guide for families and individuals affected by X and Y chromosome variations by Virginia Isaacs Cover.

References:
Davis, S., Howell, S., Wilson, R., Tanda, T., Ross, J., Zeitler, P., & Tartaglia, N. (2016). Advances in the interdisciplinary care of children with Klinefelter syndrome. Advances in Pediatrics, 63(1), 15.
Turriff, A., Levy, H. P., & Biesecker, B. (2015). Factors associated with adaptation to Klinefelter syndrome: The experience of adolescents and adults. Patient Education and Counseling, 98(1), 90-95.

47,XXY Resources

For more information about XXY and to find local, national, and online support groups, please see the following:
AXYS » genetic.org
Klinefelter Syndrome: A Guide for Families
TeensHealth: Klinefelter Syndrome

For more information about a XXY diagnosis, please see the following:
Living with Klinefelter Syndrome (47,XXY), Trisomy X (47,XXX), and 47,XYY: A Guide for Families and Individuals Affected by X and Y Chromosome Variations by Virginia Isaacs Cover.

Conclusion

Parents learning about XXY should receive accurate and up-to-date resources. This information should include common life outcomes and development, possible medical issues and treatments, and helpful services. Expectant parents should also be offered clear information about testing and pregnancy management. Together, health professionals and support groups can provide a range of information to give parents a well-rounded understanding of XXY.