Klinefelter Syndrome

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Mareike Müller is a freelance writer in the medical department and assistant doctor for neurosurgery in Düsseldorf. She studied human medicine in Magdeburg and gained a lot of practical medical experience during her stays abroad on four different continents.

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Klinefelter syndrome is a genetic disease. It only affects men. These have too many sex chromosomes in their cells. Typical symptoms are tall stature and infertility. There is no cure for Klinefelter syndrome. However, there are various medications that can be used to relieve symptoms. Read everything about Klinefelter Syndrome here!

Klinefelter syndrome: description

Klinefelter syndrome is a genetic disease that only affects men. They have at least one too many so-called sex chromosomes in their cells. The term XXY syndrome is also common.

Klinefelter syndrome is called syndrome because there are different signs of the disease that occur at the same time and are related to one another. One also speaks of a symptom complex. The characteristics of Klinefelter syndrome were first discovered in 1942 by the American doctor Dr. Harry Klinefelter described.

Klinefelter Syndrome: Occurrence

Klinefelter patients are always male. Statistically speaking, around one boy in between 500 and 1,000 live births is affected by Klinefelter syndrome. Statistical calculations suggest that around 80,000 men across Germany have Klinefelter syndrome. In only around 5000 confirmed cases, one suspects a high number of unreported cases.

Klinefelter syndrome is the most common chromosome abnormality (chromosome aberration) in men and the most common genetic cause of male infertility.

Klinefelter syndrome: symptoms

The Klinefelter syndrome varies greatly from person to person and can affect many different organ systems. Most of the time, the childhood of those affected is inconspicuous. During this time, symptoms such as:

delayed language and motor development
Learning difficulties with often normal intelligence
Tall stature with long legs

Often the Klinefelter syndrome does not become noticeable until puberty. This usually occurs with a delay or not at all:

The beard growth and secondary hair are absent or sparse.
The voice change is missing: the patients keep a high voice.
The sex drive (libido) is reduced
The testicle volume (the size of the testicles) remains small
The men are incapable of procreation
The body fat distribution is more feminine

Klinefelter syndrome: causes and risk factors

In order to better understand Klinefelter syndrome, here are some definitions of terms. Klinefelter syndrome is due to a chromosomal aberration. Doctors understand this to mean that the number or structure of the chromosomes is disrupted.

Our genetic information is stored on the chromosomes. There are normally 46 chromosomes in each cell. This also includes two sex chromosomes. In the female karyotype (set of chromosomes) they are designated as XX, in the male as XY. A normal karyotype is accordingly described as 46, XX or 46, XY.

There are more than 46 chromosomes in Klinefelter syndrome.

Klinefelter Syndrome: Different Karyotypes

Different karyotypes can lead to Klinefelter syndrome:

47, XXY: Around 80 percent of patients have an additional X chromosome in all cells of the body.
46, XY / 47, XXY: Some patients have cells with normal and changed chromosome sets in their bodies. This is called a mosaic.
48, XXXY; 48, XXYY; 49, XXXXY: There are special cases in which there is not just one additional X chromosome in the cells, but several. Additional Y chromosomes are also possible.

How does Klinefelter syndrome arise?

The cause of Klinefelter syndrome lies in the maturation of the father's sperm cells or the maturation of the mother's egg cells.

In what is known as meiosis, the chromosome pairs (XX in the egg cell, XY in the sperm cell) are separated. If this does not happen, a pair of chromosomes is completely passed on and the result is Klinefelter syndrome.

The double X chromosome disrupts the production of testosterone in the testes. Since the male sex hormone testosterone is not only important for the development of the sexual organs and characteristics, but also takes on various tasks in the human metabolism, the symptoms of Klinefelter syndrome are so diverse.

In addition, the rest of the X chromosome is partially suppressed.This mechanism is developed differently from patient to patient and ensures a different severity of symptoms.

Klinefelter Syndrome: Investigations and Diagnosis

Due to the mild symptoms in childhood, Klinefelter's syndrome is often only diagnosed during puberty and sometimes even only in adulthood when there is unwanted childlessness.

At the time of compulsory military service, affected men were noticeable in the so-called muster due to a small testicle volume. Nowadays, Klinefelter's syndrome is mainly diagnosed during the preventive medical check-up at the pediatrician, the J1.

Depending on the age, treatment is given by the pediatrician, endocrinologist or andrologist - sometimes by several disciplines together.

Klinefelter syndrome: diagnostics

In order to diagnose Klinefelter syndrome, the doctor first asks the patient in detail about their medical history (anamnesis). Here are some of the questions he'll likely ask you:

Did you have trouble keeping up at school?
Do you often feel weak?
When did your puberty begin?
Have you and your partner been trying to have a child for a long time without success?

Klinefelter Syndrome: Physical Exam

Then the doctor examines the patient physically. He first pays attention to the external appearance, especially the body proportions. Is the patient tall? Does he have longer than average legs? In addition, the doctor examines the body hair and the mammary gland.

The testicle size is also measured. It is usually significantly reduced in Klinefelter patients.

Klinefelter syndrome: blood test

After a blood sample has been taken, various hormone levels can be determined in the laboratory. Patients with Klinefelter syndrome usually have low levels of testosterone and high levels of FSH and LH in their blood. Doctors then speak of hypergonadotropic hypogonadism, i.e. an underdevelopment of the gonads despite high hormonal stimulation.

In addition, the removed blood cells can be viewed under a microscope and the number and structure of the chromosomes can be analyzed. In this way, the XXY syndrome can be easily recognized because there are (at least) three sex chromosomes instead of two.

Klinefelter syndrome: prenatal exams

The so-called prenatal diagnosis offers the possibility of diagnosing Klinefelter syndrome before birth. Such an early diagnosis offers the opportunity to optimally care for the child from birth and support it in a targeted manner.

Prenatal diagnostics include invasive examinations such as amniocentesis: the doctor takes a small sample of the amniotic fluid from the pregnant woman. This contains childish cells whose genetic material (DNA) can be analyzed for a wide variety of chromosome changes (anomalies) such as Klinefelter's syndrome. The disadvantage of invasive prenatal exams like amniocentesis is that they can trigger a miscarriage.

Non-invasive prenatal blood tests (NIPT) such as the Harmony test, PrenaTest and Panorama test do not have this disadvantage. You only need a maternal blood sample: it contains traces of the child's genome that can be checked for chromosomal abnormalities. The prenatal blood tests provide quite reliable results, but cost several hundred euros (depending on the test and the scope of the analysis).

If Klinefelter syndrome is actually found in the unborn child by means of prenatal diagnostics, this is not a reason for an abortion! The symptoms of those affected are usually mild and not life-threatening.

Klinefelter syndrome: treatment

Klinefelter syndrome is incurable because it is caused by chromosome aberration. This cannot be influenced.

So it is important to treat the symptoms of Klinefelter syndrome. The most important starting point is the low testosterone level in the blood of those affected. Therefore, the patients receive artificial testosterone for life. This is also known as testosterone substitution. Gels, plasters and syringes are available for this. Tablets are not used because the hormone breaks down quickly in the gastrointestinal tract and can lead to intolerance.

Whether a gel, patch or syringe is used also depends on the patient's preferences. Gels have the advantage of not being painful. However, they need to be applied daily. Patches should be changed every two days. Syringes are available in the form of depot syringes that only need to be administered every four weeks to three months.

Before a testosterone substitution takes place, a malignant tumor of the prostate gland (prostate carcinoma) must be excluded. Testosterone makes such tumors grow faster, so they need to be treated first.

Klinefelter syndrome: therapy control

The effectiveness of testosterone treatment should be checked regularly by taking blood samples. For this purpose, the values for testosterone and other hormones such as LH, FSH and estradiol are monitored.

The red blood cells (erythrocytes) are also examined because their formation is promoted by testosterone. In addition, the bone density should be measured every two to three years in order to detect possible osteoporosis at an early stage. In addition, the breast should be palpated regularly, as Klinefelter patients have a higher risk of breast cancer.

Successful testosterone therapy shows itself in increased performance and reduced fatigue as well as in the prevention of osteoporosis, diabetes mellitus and muscle weakness.

Klinefelter syndrome: disease course and prognosis

The symptoms of Klinefelter syndrome are usually mild. Through consistent testosterone therapy and targeted support in school, patients lead a balanced and self-determined life.

Nevertheless, it is mainly infertility that affects those affected. Klinefelter syndrome life expectancy is limited in that patients are 20 times more likely to develop breast cancer.

Patients with Klinefelter syndrome are of average intelligence. However, they often need more time to learn new things. Speech and motor development should be encouraged early on through speech therapy and occupational therapy.

Klinefelter syndrome: desire to have children

In order for Klinefelter syndrome patients to have the opportunity to father children, sperm cells can be removed from the testes in early adolescence.

At this point in time and before testosterone therapy, the chance of finding functional sperm is highest. The material obtained by testicular biopsy is analyzed, processed and frozen (cryopreservation). This makes it long-lasting and is available if you want to have children later. Then an egg cell is removed from the woman and artificially fertilized with the sperm cells.

Parents of a child with Klinefelter syndrome do not have an increased risk of another child becoming ill as well.

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