Klinefelter Syndrome

What is Klinefelter syndrome?

Klinefelter syndrome is a chromosomal condition that describes boys and men with common features, physical traits and medical conditions that are caused by the presence of an extra X chromosome (i.e., XXY).

Both males and females generally have 46 chromosomes. In females, this includes two X chromosomes, while males have one X and one Y chromosome.

What are the types of Klinefelter syndrome?

The most common form is the classic type, but there are variations.

1. Classic Klinefelter syndrome (47,XXY)
   This is the usual type, where a male has one extra X chromosome in all or most of their cells.
2. Mosaic Klinefelter syndrome
   In this type, some cells have an extra X chromosome (47,XXY), while others are normal (46,XY). This often causes milder symptoms.
3. Other variations
   Rarely, males may have more than one extra X chromosome and may result in more severe symptoms.

How common is Klinefelter syndrome?

It is estimated that one in 500 to 1,000 males are born with KIinefelter syndrome.

What are the symptoms of Klinefelter syndrome?

Klinefelter syndrome does not usually cause any obvious symptoms early in childhood, and many boys and men often do not realise they have KIinefelter syndrome until they go through puberty.

In these instances, puberty may be late or incomplete. Sometimes, the condition may only be diagnosed in adulthood due to infertility. The features of KIinefelter syndrome can vary and it is important to note that not all the features described will be seen in your child.

The typical features of KIinefelter syndrome in an adult are:

• Growth: A tall and thin body with disproportionate long arms and legs.
• Physical features: If untreated, adult individuals with Klinefelter syndrome may have breast tissue development (gynaecomastia), female pattern of fat distribution and reduced facial and body hair.
• Small testicles:  This feature may be found in individuals with Klinefelter syndrome.

Children and adolescents with KIinefelter syndrome may experience:

• Learning difficulties  
  • Delayed motor development
  • Difficulties with speech and reading
  • Poor muscle tone
  • Lower attention span
     
• Behavioural problems

In adulthood, in addition to the main typical features, untreated adults may have:

• Hypogonadism. Individuals with Klinefelter syndrome often have reduced testosterone production.
  
  Testosterone is important for normal reproductive and sexual function, and physical changes that happen during male puberty such as development of the penis and testes, and facial and body hair. It also helps the growth of bone and muscles.
  
  Hence, men with KIinefelter syndrome have underdeveloped testes, low libido (sex drive), infertility and osteoporosis (thinning of the bones).
  
  Many men with Klinefelter syndrome will have infertility, and may require assisted reproductive technologies to conceive.
  
  
• Intelligence. Most men with  KIinefelter syndrome have normal intelligence, though some may have their intelligence affected.
  

Some individuals with Klinefelter syndrome may find it beneficial to connect with others who share similar experiences and concerns for psychosocial support.

What are other medical concerns associated with Klinefelter syndrome?

The following problems can also be seen in individuals with KIinefelter syndrome and need to be monitored for and treated if present:

• Cardiovascular diseases such as ischaemic heart disease, peripheral vascular disease and pulmonary embolism
• Metabolic syndromes such as dyslipidaemia and diabetes mellitus
• Breast cancer
• Thromboembolism (blood clots in blood vessels)
• Autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis and Sjogren’s syndrome

When should you see a doctor?

If you notice symptoms of Klinefelter syndrome in yourself or your child, please consult a healthcare professional or specialist for further testing and diagnosis.  

What causes Klinefelter syndrome?

Klinefelter syndrome is caused by a random genetic error that results in a male having an extra X chromosome. Normally, males have one X and one Y chromosome (46,XY), but individuals with Klinefelter syndrome have an additional X chromosome (47,XXY). This extra chromosome occurs due to an error during the formation of sperm or egg cells.

The condition is not inherited and happens spontaneously during the process of cell division. In some cases, the chromosomal abnormality may occur after fertilisation, leading to mosaic klinefelter syndrome, where some cells have the typical 46, XY chromosomes, and others have 47, XXY.

What are the risk factors for Klinefelter syndrome?

Women above the age of 35 when they become pregnant have a slightly higher chance of having a child with chromosomal abnormalities, including Klinefelter syndrome. However, this increased risk is small.

There are no specific lifestyle or environmental factors that increase the likelihood of Klinefelter syndrome, as it results from random errors in cell division. Since the condition is not inherited, family history does not typically play a role.

How is Klinefelter syndrome diagnosed?

The diagnosis of KIinefelter syndrome is made by looking at the complete set of chromosomes of the individual. This is called a karyotype. A karyotype shows the number and visual appearance of the chromosomes found in the cells of a person.

• Before birth
  Diagnosis can be made by taking a sample of amniotic fluid, or other foetal tissue, to look at the foetal karyotype.
• After birth
  Diagnosis is confirmed by taking a sample of blood or other tissue to obtain a karyotype.

Karyotype showing KIinefelter syndrome

Can Klinefelter syndrome be cured?

While it is not possible to cure KIinefelter syndrome, much can be done to make sure your child has the best possible outcome.

How is Klinefelter syndrome managed?

The multidisciplinary medical team will be able to address specific medical concerns and routine KIinefelter syndrome -related healthcare issues.

Below are some related medical issues and how they can be managed:

Early intervention therapies for developmental delays

Speech and occupational therapy are helpful for children and adults who experience delays in speech or challenges with motor skills.

Learning difficulties can also often be managed through tailored educational programmes and support from teachers or specialists.

Testosterone therapy

If needed, testosterone therapy is usually started from puberty and continued through adulthood.

Testosterone replacement can help to:

• Allow normal and complete pubertal development
• Promote feelings of well-being

Assisted reproductive therapy

Although most individuals with Klinefelter syndrome are infertile, some may be able to father children through assisted reproductive techniques, such as testicular sperm extraction (TESE) combined with in vitro fertilisation (IVF).

Counselling and emotional support

Therapy or counselling can help manage emotional challenges, low self-esteem and social difficulties. Support groups may also provide valuable assistance.

Regular medical check-ups

Regular medical check-ups are essential to monitor health and address potential complications, such as osteoporosis or cardiovascular issues. Early intervention and consistent care can significantly improve outcomes for individuals with Klinefelter syndrome.

Klinefelter syndrome is a lifelong condition. Should you require financial assistance or emotional support, please approach your doctor for referral to a medical social worker.

This information does not replace medical advice from your medical professional. Please consult with your doctor should you have further questions.

Download the Klinefelter Syndrome brochure.

References

47, XXY (klinefelter syndrome) - symptoms, causes, treatment. National Organization for Rare Disorders. (2024, July 15). https://rarediseases.org/rare-diseases/47-xxy-klinefelter-syndrome/

About klinefelter syndrome. Genome.gov. (n.d.). https://www.genome.gov/Genetic-Disorders/Klinefelter-Syndrome

Osunkoya, A. O. (2023). Klinefelter syndrome. Uropathology, 460–461. https://doi.org/10.1016/b978-0-323-65395-4.00216-5

Ross, J. L. (Ed.). (2021, September). Klinefelter syndrome (for parents) | nemours kidshealth. KidsHealth. https://kidshealth.org/en/parents/klinefelter-syndrome.html