Klinefelter syndrome

Overview

Klinefelter syndrome is a genetic condition that results when a boy is born with an extra copy of the X chromosome. Klinefelter syndrome is a genetic condition affecting males, and it often isn't diagnosed until adulthood.

Klinefelter syndrome may adversely affect testicular growth, resulting in smaller than normal testicles, which can lead to lower production of testosterone. The syndrome may also cause reduced muscle mass, reduced body and facial hair, and enlarged breast tissue. The effects of Klinefelter syndrome vary, and not everyone has the same signs and symptoms.

Most men with Klinefelter syndrome produce little or no sperm, but assisted reproductive procedures may make it possible for some men with Klinefelter syndrome to father children.

Symptoms

Signs and symptoms of Klinefelter syndrome vary widely among males with the disorder. Many boys with Klinefelter syndrome show few or only mild signs. The condition may go undiagnosed until adulthood or it may never be diagnosed. For others, the condition has a noticeable effect on growth or appearance.

Signs and symptoms of Klinefelter syndrome also vary by age.

Babies

Signs and symptoms may include:

• Weak muscles
• Slow motor development — taking longer than average to sit up, crawl and walk
• Delay in speaking
• Problems at birth, such as testicles that haven't descended into the scrotum

Boys and teenagers

Signs and symptoms may include:

• Taller than average stature
• Longer legs, shorter torso and broader hips compared with other boys
• Absent, delayed or incomplete puberty
• After puberty, less muscle and less facial and body hair compared with other teens
• Small, firm testicles
• Small penis
• Enlarged breast tissue (gynecomastia)
• Weak bones
• Low energy levels
• Tendency to be shy and sensitive
• Difficulty expressing thoughts and feelings or socializing
• Problems with reading, writing, spelling or math

Men

Signs and symptoms may include:

• Low sperm count or no sperm
• Small testicles and penis
• Low sex drive
• Taller than average height
• Weak bones
• Decreased facial and body hair
• Less muscular compared with other men
• Enlarged breast tissue
• Increased belly fat

When to see a doctor

See a doctor if you or your son has:

• Slow development during infancy or boyhood. Delays in growth and development can be the first sign of a number of conditions that need treatment — including Klinefelter syndrome. Though some variation in physical and mental development is normal, it's best to check with a doctor if you have any concerns.
• Male infertility. Many men with Klinefelter syndrome aren't diagnosed with infertility until they realize they're unable to father a child.

Causes

Klinefelter syndrome occurs as a result of a random error that causes a male to be born with an extra sex chromosome. It isn't an inherited condition.

Humans have 46 chromosomes, including two sex chromosomes that determine a person's sex. Females have two X sex chromosomes (XX). Males have an X and a Y sex chromosome (XY).

Klinefelter syndrome can be caused by:

• One extra copy of the X chromosome in each cell (XXY), the most common cause
• An extra X chromosome in some of the cells (mosaic Klinefelter syndrome), with fewer symptoms
• More than one extra copy of the X chromosome, which is rare and results in a severe form

Extra copies of genes on the X chromosome can interfere with male sexual development and fertility.

Risk factors

Klinefelter syndrome stems from a random genetic event. The risk of Klinefelter syndrome isn't increased by anything a parent does or doesn't do. For older mothers, the risk is higher but only slightly.

Complications

Klinefelter syndrome may increase the risk of:

• Anxiety and depression
• Social, emotional and behavioral problems, such as low self-esteem, emotional immaturity and impulsiveness
• Infertility and problems with sexual function
• Weak bones (osteoporosis)
• Heart and blood vessel disease
• Breast cancer and certain other cancers
• Lung disease
• Metabolic syndrome, which includes type 2 diabetes, high blood pressure (hypertension), and high cholesterol and triglycerides (hyperlipidemia)
• Autoimmune disorders such as lupus and rheumatoid arthritis
• Tooth and oral problems that make dental cavities more likely
• Autism spectrum disorder

A number of complications caused by Klinefelter syndrome are related to low testosterone (hypogonadism). Testosterone replacement therapy reduces the risk of certain health problems, especially when therapy is started at the beginning of puberty.

Diagnosis

Your doctor will likely do a thorough physical exam and ask detailed questions about symptoms and health. This may include examining the genital area and chest, performing tests to check reflexes, and assessing development and functioning.

The main tests used to diagnose Klinefelter syndrome are:

• Hormone testing. Blood or urine samples can reveal abnormal hormone levels that are a sign of Klinefelter syndrome.
• Chromosome analysis. Also called karyotype analysis, this test is used to confirm a diagnosis of Klinefelter syndrome. A blood sample is sent to the lab to check the shape and number of chromosomes.

A small percentage of males with Klinefelter syndrome are diagnosed before birth. The syndrome might be identified in pregnancy during a procedure to examine fetal cells drawn from the amniotic fluid (amniocentesis) or placenta for another reason — such as being older than age 35 or having a family history of genetic conditions.

Klinefelter syndrome may be suspected during a noninvasive prenatal screening blood test. To confirm the diagnosis, further invasive prenatal testing such as amniocentesis is required.

Treatment

If you or your son is diagnosed with Klinefelter syndrome, your health care team may include a doctor who specializes in diagnosing and treating disorders involving the body's glands and hormones (endocrinologist), a speech therapist, a pediatrician, a physical therapist, a genetic counselor, a reproductive medicine or infertility specialist, and a counselor or psychologist.

Although there's no way to repair the sex chromosome changes due to Klinefelter syndrome, treatments can help minimize its effects. The earlier a diagnosis is made and treatment is started, the greater the benefits. But it's never too late to get help.

Treatment for Klinefelter syndrome is based on signs and symptoms and may include:

• Testosterone replacement therapy. Starting at the time of the usual onset of puberty, testosterone replacement therapy can be given to help stimulate changes that normally occur at puberty, such as developing a deeper voice, growing facial and body hair, and increasing muscle mass and sexual desire (libido). Testosterone replacement therapy can also improve bone density and reduce the risk of fractures, and it may improve mood and behavior. It will not improve infertility.
• Breast tissue removal. In males who develop enlarged breasts, excess breast tissue can be removed by a plastic surgeon, leaving a more typical-looking chest.
• Speech and physical therapy. These treatments can help boys with Klinefelter syndrome who have problems with speech, language and muscle weakness.
• Educational evaluation and support. Some boys with Klinefelter syndrome have trouble learning and socializing and can benefit from extra assistance. Talk to your child's teacher, school counselor or school nurse about what kind of support might help.
• Fertility treatment. Most men with Klinefelter syndrome are typically unable to father children because few or no sperm are produced in the testicles. For some men with minimal sperm production, a procedure called intracytoplasmic sperm injection (ICSI) may help. During ICSI, sperm is removed from the testicle with a biopsy needle and injected directly into the egg.
• Psychological counseling. Having Klinefelter syndrome can be a challenge, especially during puberty and young adulthood. For men with the condition, coping with infertility can be difficult. A family therapist, counselor or psychologist can help work through the emotional issues.

Coping and support

Treatment, health education and social support can greatly benefit individuals with Klinefelter syndrome.

Boys with Klinefelter syndrome

If you have a son with Klinefelter syndrome, you can help promote healthy mental, physical, emotional and social development.

• Learn about Klinefelter syndrome. Then you can provide accurate information, support and encouragement.
• Monitor your son's development carefully. Seek help for problems you notice, such as trouble with speech or language.
• Keep regular follow-up appointments with medical professionals. This may help prevent future problems.
• Encourage participation in sports and physical activities. These activities will help build muscle strength and motor skills.
• Encourage social opportunities and participation in group activities. These activities can help develop social skills.
• Work closely with your son's school. Teachers, school counselors and administrators who understand your son's needs can make a big difference.
• Learn what support is available. For example, ask about special education services, if needed.
• Connect with other parents. Klinefelter syndrome is a common condition, and you — and your son — aren't alone. Ask your doctor about internet resources and support groups that may help answer questions and ease concerns.

Men with Klinefelter syndrome

If you have Klinefelter syndrome, you may benefit from these self-care measures:

• Work closely with your doctor. Appropriate treatment can help you maintain your physical and mental health and prevent problems later in life, such as osteoporosis.
• Investigate your options for planning a family. You and your partner may want to talk to a doctor or other health professional about your options.
• Talk with others who have the condition. There are a number of resources that provide information about Klinefelter syndrome and can offer the perspectives of other men and their partners who cope with the condition. Many men also find it helpful to join a support group.

Preparing for an appointment

If you notice symptoms of Klinefelter syndrome in yourself or your son, talk to your health care professional. You may be referred to a specialist for testing and diagnosis.

Here's some information to help you get ready for your appointment. If possible, bring a family member or friend with you. A trusted companion can help you remember information and provide emotional support.

What you can do

Before the appointment, make a list of:

• Signs or symptoms that concern you
• Medications, including over-the-counter medications, vitamins, herbs or other supplements, and the dosages
• Ages when you or your son reached certain puberty milestones, such as the development of pubic and armpit hair, growth of the penis, and increased testicle size
• Questions to ask the doctor to make the most of your appointment

Questions to ask might include:

• Do the symptoms indicate Klinefelter syndrome?
• What tests are needed to confirm the diagnosis?
• What are other possible causes for the symptoms?
• Is a specialist needed?
• What treatments are necessary?
• What are the side effects and expected results of treatment?
• What kind of special therapies do you recommend?
• What kind of support is available?
• How can I learn more about this disorder?

Don't hesitate to ask other questions during the appointment.

What to expect from your doctor

Your doctor may ask questions such as:

• When did you first notice that something may be wrong?
• What signs and symptoms have you noticed?
• When did you (or your child) meet growth and developmental milestones?
• Do you have problems with fertility?
• Have you had any previous tests or treatments?