Klinefelter syndrome: What you need to know

Klinefelter syndrome: Symptoms, diagnosis, and treatment

By Kanna Ingleson   

Reviewed by Karen Gill, MD
Klinefelter syndrome is a
genetic disorder that affects the development of the testes and, as a result,
testosterone production. It is also known as XXY syndrome and was previously
sometimes called XXY trisomy.

The most common symptom of
Klinefelter syndrome (KS) in adult males is infertility. KS is also sometimes
associated with language processing problems and learning disabilities.

 In this article, we look at the causes,
symptoms, diagnosis, and treatment of KS.

Typically, females have two X
chromosomes, and males have one X and one Y chromosome.
KS occurs when a male child is
born with at least one extra X chromosome. This imbalance happens due to an error
during egg or sperm development and results in a male having an extra X
chromosome in all of his body’s cells. KS is also called XXY syndrome.
Although KS is a genetic
disorder, the inclusion of the extra X chromosome is a random genetic event and
is not directly inherited. KS is found in about 1 in 500 to 1,000 newborn
Current knowledge of KS
symptoms comes from people who need treatment, and they usually have the most
severe symptoms. However, a relatively small number of people have KS, which is
one of the reasons why diagnosis of the disorder is sometimes missed.

Small testes are the main sign
of KS and are present in all cases. Symptoms do not all occur at the same time
but at different times during the lifetime of the person with KS. Symptoms
appear to worsen over time.
Boys with KS tend to be quiet,
sensitive, and unassertive. When they get older, they may be taller than other
boys and have more belly fat than their peers.
People with KS might be slow
to learn to talk, read, and write, and they might have difficulty processing
what they hear.
Also, males with KS may have:

  • low testosterone levels
  • low sex drive
  • infertility
  • breast development
  • reduced muscle mass
  • broad hips
  • reduced body hair

Although infertility is the
most common outcome of KS, males can also be at greater risk of developing the
following complications:

  • heart disease
  • diabetes
  • osteoporosis
  • autoimmune disorders
    (including lupus)
  • cancer (including breast
  • lung disease
  • varicose veins
  • dental cavities
  • anxiety and depression

Only a genetic test can
conclusively diagnose KS. The test is called a karyotype. A small skin or blood
sample is sent to a laboratory to find out if there is an extra X chromosome.
Learning difficulties may be
the first indication that a child has KS. In adult males, infertility is often
the first sign that KS may be present.
Once puberty has started, a
physical examination of the chest and testes can reveal the physical symptoms
of KS, such as small testes and enlarged breasts.
Further investigation may
include a sperm count for reduced fertility and a hormone test for reduced
KS may be severely
under-diagnosed because doctors overlook some of its symptoms, which are
similar to the symptoms of other disorders.
Only 10 percent of cases are
diagnosed in childhood, and it is thought that only about 25 percent of all
males with KS are ever diagnosed. On average, males with KS are not diagnosed
until their mid-30s.

Chromosomal abnormalities due
to KS cannot be corrected, and there is no cure. However, treatment can be
effective in reducing symptoms.
While early diagnosis will
help manage some of the chronic aspects of KS, it is never too late to start
treatment for KS. Treatment can bring benefits at any age and may include the
Testosterone replacement
Treatment is usually in the
form of an injection, pills, gel, or a patch. Testosterone replacement therapy
improves, strength, body hair growth, energy, and concentration.
Starting treatment early,
usually at the onset of puberty, can prevent the long-term effects of reduced
testosterone production.
Testosterone therapy does not
improve testicle size or fertility.
Fertility treatment
Between 95 and 99 percent of
males with KS are infertile because they do not produce enough sperm to
fertilize an egg. However, more than 50 percent of males with KS do have sperm.
For men with minimal sperm
production, an intracytoplasmic sperm injection (ICSI) can be effective. During
an ICSI, sperm is removed from the testicle and injected directly into the egg.
If diagnosed early enough,
semen or testicular tissue can be preserved before the testicular damage
starts, probably at puberty. This method is called cryopreservation, and it
uses very low temperatures to preserve living cells and tissues for later use.
Breast reduction surgery
There is no approved drug
treatment for overdeveloped breast tissue in males. Removal of the breast
tissue by a plastic surgeon is effective but comes with the risks associated
with any surgery.
The result of breast reduction
surgery is a chest that appears typically more masculine. It reduces the
chances of developing breast cancer and can help alleviate the social stress
associated with enlarged breasts in males.
Psychological counseling
Dealing with the symptoms of
KS can be embarrassing and challenging for males, especially during puberty and
early adulthood.
Coping with infertility can
also be difficult, and a counselor or psychologist can help people to process
and reduce emotional issues associated with KS.
A male counsellor with a male
Psychological counseling and
speech therapy may be helpful to those living with KS.
Therapeutic support
The right support at the right
time can help prevent difficulties with language, schooling, and social
interaction. Additional therapeutic support may include:

  • speech and physical therapy
  • educational evaluation and
  • occupational therapy
  • behavioral therapy

Most people with KS will live
a normal, productive life. Symptoms can be mild enough to go unnoticed.
In cases where symptoms are
clear and sometimes distressing, the right treatment at the right time can go a
long way towards reducing or even preventing the effects of KS.
More work is needed to improve
the rate of diagnosis and to provide better evidence for the timing and
application of testosterone replacement therapy.
Treatment of KS can also
benefit from the input of healthcare providers with different areas of
expertise. Ideally, treatment will include pediatricians, speech therapists,
general practitioners, psychologists, infertility specialists, urologists, and
Researchers at Columbia
University Medical Center in New York, NY, are currently developing a new
assessment tool to help doctors spot the physical traits of KS and to start
treatment early.
Kayode Ojo
Kayode Emmanuel Ojo is the Co-Founder and Managing Director at SHEFFA Limited. He is presently studying Computer Science at the National Open University, Victoria Island, Lagos.