Klinefelter’s Syndrome

Klinefelter’s syndrome is a common genetic condition affecting males who are born with at least one extra X chromosome, leading to a wide range of physical and developmental differences that many may not even realize they have.

Table of contents

• What is Klinefelter’s Syndrome?
• What causes this condition?
• How common is Klinefelter’s syndrome?
• Signs and symptoms
• Associated health problems
• How is it diagnosed?
• Treatment options
• Living with Klinefelter’s syndrome

What is Klinefelter’s Syndrome?

Klinefelter’s syndrome is a genetic condition that affects males and results from having at least one extra X chromosome in their cells^[1]. Most males have 46 chromosomes (packages of genetic material found in every cell) in each cell, which includes one X and one Y chromosome, written as 46,XY. Males with Klinefelter’s syndrome have a total of 47 chromosomes, with two X chromosomes and one Y chromosome, written as 47,XXY^[3].

The condition is also commonly known as XXY syndrome. The X chromosome is not a “female” chromosome and is present in everyone. The presence of a Y chromosome determines male sex, so boys and men with Klinefelter’s syndrome are still genetically male^[2].

XXY syndrome, 47,XXY

What causes this condition?

Klinefelter’s syndrome occurs when there is an extra X chromosome in a male’s genetic code. This change happens before birth and can happen in a few different ways^[3]. The extra X chromosome can come from either the mother’s egg or the father’s sperm carrying an extra X chromosome. About half the time the error occurs during sperm formation, and the remainder occurs during egg development^[9].

In some cases, cells divide incorrectly during early development before birth. Healthcare providers call this mosaic Klinefelter syndrome, which occurs when some cells in the body have an extra X chromosome while others have the typical XY pattern^[3]. Boys and men with mosaic Klinefelter syndrome often have milder symptoms than others with the condition^[2].

Klinefelter syndrome is not caused by anything the parents did or did not do. The disorder is a random error in cell division that happens when reproductive cells are being formed^[6]. If you have a son with the condition, the chances of this happening again are very small. However, women who have pregnancies after age 35 have a slightly increased chance of having a boy with this syndrome^[9].

Klinefelter syndrome is not directly inherited. The additional X chromosome occurs randomly, and after conception, the chromosome pattern becomes XXY rather than XY^[2].

How common is Klinefelter’s syndrome?

Klinefelter’s syndrome is fairly common, occurring in about 1 in 500 to 1 in 650 males^[4]. However, many people with this condition may never be diagnosed. Researchers believe that up to 65 percent of people with Klinefelter syndrome are never diagnosed^[4]. Some experts estimate that 70% to 80% of males with the condition likely don’t know they have it^[3].

It is the most common sex chromosome disorder, which is a group of conditions caused by changes in the number of sex chromosomes^[4].

Signs and symptoms

The symptoms of Klinefelter’s syndrome vary widely. Many children with Klinefelter syndrome show few or only mild symptoms. Most often the condition isn’t diagnosed until puberty or adulthood, or it may never be diagnosed^[1]. Some males have no symptoms or very mild symptoms, so they might not know that they have the condition and lead normal lives^[2].

In babies and toddlers

Babies with Klinefelter syndrome typically have weak muscles, reduced strength, and quiet personalities. They also can take longer to do things like sit up, crawl, walk, and speak^[6]. Other possible features include:

• Problems at birth, such as testicles that haven’t dropped into the scrotum
• A smaller penis
• Undescended testicles
• Learning to sit up, crawl, walk and talk later than usual
• Being quieter and more passive than usual^[2]

In childhood

Children with Klinefelter’s syndrome may have difficulties that are not immediately obvious. Possible features include:

• Shyness and low self-confidence
• Problems with reading, writing, spelling and paying attention
• Mild dyslexia or dyspraxia
• Low energy levels
• Difficulty socializing or expressing feelings^[2]
• Learning and language problems, such as trouble with reading, writing, spelling or math
• Speaking later than other children of the same age^[1]

In teenagers

During puberty, the symptoms of Klinefelter’s syndrome may become more noticeable. Teenagers may experience:

• Growing taller than expected for the family (with long arms and legs)
• Broad hips
• Longer legs, shorter body, narrower shoulders compared with other children
• Poor muscle tone and slower than usual muscle growth
• Reduced facial and body hair that starts growing later than usual
• Small, firm testes
• Enlarged breasts, called gynecomastia (breast tissue growth in males)
• Delayed or incomplete puberty^[2]

In adults

Adults with Klinefelter’s syndrome may have:

• Small, firm testes
• Inability to have children naturally (infertility)
• Low sex drive
• Erection problems
• Less facial and body hair
• Extra breast tissue^[2]

Most males with Klinefelter syndrome produce little or no sperm, but assisted reproductive procedures may make it possible for some people with Klinefelter syndrome to have biological children^[1].

Neurological and developmental symptoms

Beyond physical symptoms, Klinefelter’s syndrome can affect behavior, learning, and mental health. These symptoms may include:

• Depression and anxiety
• Social, emotional or behavioral issues
• Impulsive behaviors
• Learning differences like reading and language challenges
• Attention-deficit/hyperactivity disorder (ADHD)
• Speech delays
• Autism spectrum disorder^[3]

Children with Klinefelter syndrome may have low muscle tone, difficulty coordinating movements, and mild delays of certain developmental skills. People with Klinefelter syndrome tend to have better receptive language skills (the ability to understand speech) than expressive language skills (vocabulary and the production of speech)^[4].

Associated health problems

Many boys and men with Klinefelter syndrome will not be significantly affected and can live normal, healthy lives. Infertility tends to be the main problem, although there are treatments that can help^[2].

However, men with Klinefelter syndrome are at a slightly increased risk of developing other health problems. People with Klinefelter syndrome have a higher risk of developing certain metabolic syndromes, including:

• Obesity (body mass index greater than 30)
• Hypertension (high blood pressure)
• Type 2 diabetes
• High cholesterol
• High triglycerides (a type of fat in your blood)^[3]

Additionally, people with Klinefelter syndrome are more likely to develop:

• Weak and fragile bones (osteoporosis)
• Cardiovascular disease and blood clots
• Autoimmune disorders (where the immune system mistakenly attacks the body), such as lupus or rheumatoid arthritis
• An underactive thyroid gland (hypothyroidism)
• Anxiety, learning difficulties and depression
• Male breast cancer – although this is very rare^[2]
• Involuntary trembling (tremors) in their arms or hands^[4]

These problems can usually be treated if they do occur, and testosterone replacement therapy may help reduce the risk of some of them^[2].

How is it diagnosed?

To diagnose Klinefelter syndrome, a healthcare professional does a physical exam and asks questions about symptoms and health. This may include looking at the genital area and chest and talking about development and functioning^[10].

The main tests used to diagnose Klinefelter syndrome are:

• Hormone testing: Blood tests can show hormone level changes that are a sign of Klinefelter syndrome. These tests measure reproductive hormone levels^[10].
• Chromosome analysis (karyotype): This test can confirm a diagnosis of Klinefelter syndrome. A blood sample is sent to the lab to check the shape and number of chromosomes^[10].

In many cases, Klinefelter syndrome is only detected if a man with the condition undergoes fertility tests^[2].

Diagnosis before birth

Healthcare professionals sometimes diagnose Klinefelter syndrome before birth when testing is done for another reason. The syndrome can be found during pregnancy during a procedure to look at fetal cells taken from the fluid around the baby or from the placenta. These tests may be done for pregnant people who are older than age 35 or have a family history of genetic conditions^[10].

Klinefelter syndrome may be suspected during a noninvasive prenatal screening blood test. This test looks at cell-free DNA in the pregnant person’s blood sample. To confirm the diagnosis, more-invasive prenatal testing is needed^[10].

Treatment options

There is no cure for Klinefelter syndrome, but treatments can help lessen its effects. The earlier treatment is started, the better. If treatment is started by early puberty, it will likely help in reducing the symptoms^[1].

If you or your child is diagnosed with Klinefelter syndrome, your healthcare team may include several specialists. Your team may include a doctor called an endocrinologist (a specialist in conditions involving the body’s glands and hormones), a speech therapist, a pediatrician, a physical therapist, a genetic counselor, a reproductive medicine or infertility specialist, and a counselor or psychologist^[10].

Testosterone replacement therapy

Males with Klinefelter syndrome can be given testosterone, a hormone needed for sexual development. If treatment is started around the age of puberty, it can help boys with the sexual development of their bodies. Testosterone is given by injection or through a skin patch or gel^[13].

Testosterone replacement therapy corrects testosterone deficiency. The treatment promotes normalization of body proportions and development of normal male secondary sex characteristics. Regularly scheduled testosterone treatment promotes strength and facial hair growth, builds a more muscular body type, increases sexual desire, enlarges the testes, improves mood, self-image, and behavior, and protects against early osteoporosis^[14].

The treatment usually continues throughout a person’s life but does not help infertility^[13]. However, testosterone therapy may help reduce the risk of some of the associated health problems^[2].

Fertility treatment

People with Klinefelter syndrome commonly experience infertility. If you receive a Klinefelter diagnosis, you should see a fertility specialist (preferably before starting testosterone). If your provider finds sperm, they may be able to collect and freeze it in case you want to have biological children later in life^[3].

In some cases, fertility treatments may help men with Klinefelter syndrome father children. Up to half of people with Klinefelter syndrome may be able to have children using assisted reproductive technologies^[4].

Surgery

Surgery may be recommended to remove or reduce enlarged breast tissue (gynecomastia) if it causes discomfort or embarrassment^[12].

Therapy and support services

Possible treatments to address developmental and learning challenges include:

• Speech and language therapy
• Physical therapy
• Behavioral therapy
• Occupational therapy
• Educational support^[12]

Speech therapy and educational support can help children who have language or learning problems^[13].

Living with Klinefelter’s syndrome

Even without treatment, most boys with Klinefelter syndrome grow up to live productive, healthy lives^[6]. Many people with an extra X chromosome are not aware that they have it, and they lead normal lives^[9].

If your child has been diagnosed with Klinefelter syndrome, there are several ways you can help:

• Recognize your feelings: It is natural for parents to feel concerned. Allow yourself time to deal with your feelings, and talk with your child’s doctor about your concerns.
• Educate yourself about the condition: Learning about Klinefelter syndrome will help you understand how to help your child.
• Support your child: Provide age-appropriate education about Klinefelter syndrome and give them the emotional support and encouragement they need. Remind them that most people who have Klinefelter syndrome go through life with few problems.
• Be actively involved in your child’s care: Talk with your doctor about the treatment. If counseling for behavioral problems is needed, or if your child has difficulty reading or has poor verbal skills, get help from qualified professionals.
• Encourage physical activity: Encourage your child to take part in activities to improve physical motor skills, such as karate, soccer, basketball, baseball, or swimming.
• Work with teachers: Contact teachers on a regular basis to compare how your child is doing at home and at school. When appropriate, let your child be present for talks with teachers.
• Encourage independence: Although it is important to be supportive, realize that watching over your child too much can send the message that you think they are not able to do things on their own^[27].

Early diagnosis and treatment can help prevent health problems in the future. Treatment can help reduce some of the symptoms if necessary^[2].