Klinefelter’s syndrome

Klinefelter syndrome: description

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

Klinefelter syndrome is referred to as a syndrome because there are several signs of the disease that occur simultaneously and are related. It is also called a symptom complex. The Klinefelter syndrome features were first introduced in 1942 by the US physician Dr. Harry Klinefelter described.

Klinefelter syndrome: occurrence

Klinefelter patients are always male. About one boy in 500 to 1000 live births is statistically affected by Klinefelter syndrome. Statistical calculations suggest that approximately 80,000 men throughout Germany suffer from Klinefelter syndrome. With only about 5,000 confirmed cases, one suspects a high number of unreported cases.

Klinefelter syndrome is the most common male chromosome aberration and the most common genetic cause of male infertility.

Klinefelter syndrome: symptoms

The Klinefelter syndrome is individually very differently pronounced and can affect many different organ systems. Most of the childhood of the affected runs inconspicuous. During this time, symptoms may show up like:

• delayed linguistic and motor development
• Learning difficulties with often normal intelligence
• Tall growth with long legs

Frequently, the Klinefelter syndrome is noticeable only in puberty. This usually occurs delayed or not at all:

• The beard and the secondary hair stay out or are sparse.
• The voice break is missing: the patients keep a high voice.
• The sex drive (libido) is diminished
• The testicle volume (the testicle size) remains low
• The men are not capable of reproduction
• Body fat distribution is more female

In addition, further problems can occur:

• Anemia
• Osteoporosis (bone loss)
• muscle weakness
• Diabetes mellitus (diabetes)
• Thrombosis (closure of vessels)
• Tiredness, listlessness
• Gynecomastia (enlargement of the mammary glands)

Klinefelter syndrome: causes and risk factors

To better understand the Klinefelter syndrome, here are some explanations. Klinefelter syndrome is based on chromosome aberration. This is understood by physicians that the number or structure of the chromosomes is disturbed. On the chromosomes are stored our genetic information. Normally there are 46 chromosomes in each cell. These include two sex chromosomes. In the female karyotype (chromosome set), they are referred to as XX, in the male as XY. A normal karyotype is accordingly described as 46, XX and 46, XY, respectively. Klinefelter syndrome has more than 46 chromosomes.

Klinefelter Syndrome: Different types of karyotypes

Different karyotypes can lead to Klinefelter syndrome:

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

How does Klinefelter syndrome develop?

The cause of Klinefelter syndrome is the maturation of the father’s sperm or the maturing of the mother’s eggs. In so-called 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 Klinefelter syndrome develops.

Due to the double X chromosome, the formation of testosterone in the testes is disturbed. Since the male sex hormone testosterone is not only important for the development of the sexual organs and characteristics, but takes over various tasks in the metabolism of humans, the Klinefelter syndrome symptoms are so diverse. In addition, the rest of the X chromosome is partially suppressed. This mechanism varies in severity from patient to patient and ensures a different degree of symptom severity.

Klinefelter syndrome: examinations and diagnosis

Due to mild childhood symptoms, Klinefelter syndrome is often diagnosed only during adolescence and sometimes even as early as unwanted childlessness in adulthood.

At times of compulsory military service affected men in the so-called muster by a small testicle volume. Nowadays, the Klinefelter syndrome is mainly diagnosed at the check-up of adolescents with the pediatrician, the J1. Depending on the age, there is treatment by the pediatrician, endocrinologist or andrologist – sometimes also by several specialties together.

Klinefelter syndrome: diagnostics

In order to diagnose Klinefelter’s syndrome, the doctor first of all asks the patient in detail about his medical history (anamnesis). Among other things, he probably asks you the following questions:

• Did you have difficulties in coming to school?
• Do you often feel tired?
• When did your puberty begin?
• Are you and your partner trying to have a child for a long time without success?

Klinefelter Syndrome: Physical Examination

The doctor then examines the patient physically. He pays attention to the external appearance, especially the body proportions. Is the patient tall? Does he have above average legs? In addition, the doctor examines the body hair and the mammary gland. In addition, the testicle size is measured. It is usually significantly reduced in Klinefelter patients.

Klinefelter syndrome: blood test

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

In addition, the blood cells taken can be viewed under a microscope and the number and structure of the chromosomes can be analyzed. Thus, the XXY syndrome can be easily recognized, as there are at least three sex chromosomes (at least).

Klinefelter syndrome: prenatal examinations

The so-called prenatal diagnosis offers the opportunity to diagnose a Klinefelter syndrome even before birth. Such an early diagnosis offers the chance to optimally care for the child from birth and to promote it in a targeted way.

Count on prenatal diagnosis invasive examinations like the amniocentesis (amniocentesis): The doctor takes the pregnant woman a small sample of the amniotic fluid. This contains children’s cells whose genetic material (DNA) can be analyzed for a wide variety of chromosome changes (anomalies) such as Klinefelter syndrome. The disadvantage of invasive prenatal examinations such as amniocentesis is that they can cause a miscarriage.

Have this disadvantage non-invasive prenatal blood tests like the Harmony test, PraenaTest and Panorama test not. You only need one maternal blood sample: it contains traces of childhood genetic material that can be checked for chromosomal abnormalities. The prenatal blood tests provide quite reliable results, but cost (depending on the test and analysis scope) several hundred euros. These costs usually have to be borne by pregnant women – in addition to the costs of the necessary medical services (genetic counseling, blood collection, education). Only in some cases, some health insurance companies take the costs if there is an increased risk for a chromosome anomaly in an unborn baby.

Note: If the unborn child is actually diagnosed with Klinefelter syndrome by means of prenatal diagnosis, this is no reason for a termination of pregnancy! The symptoms of those affected are usually mild and not life-threatening.

Klinefelter syndrome: treatment

Klinefelter syndrome is not curable because it is caused by chromosome aberration. This can not be influenced. So it’s important to treat the symptoms of Klinefelter syndrome. The most important starting point is the low testosterone levels in the blood of those affected. Therefore, patients receive artificial testosterone for life. This is also called testosterone substitution. There are gels, patches and syringes available. Tablets are not used as the hormone in the gastrointestinal tract breaks down quickly and can lead to intolerance.

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

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

Klinefelter syndrome: therapy control

The effectiveness of the testosterone treatment should be checked regularly by taking a blood sample. It will monitor the levels of testosterone and other hormones such as LH, FSH and estradiol.

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

Successful testosterone therapy is associated with increased performance and reduced fatigue, prevention of osteoporosis, diabetes mellitus and muscle weakness.

Klinefelter syndrome: disease course and prognosis

Klinefelter syndrome usually has mild symptoms. Through consistent testosterone therapy and targeted support in school, patients lead a balanced and self-determined life. Nevertheless, especially the infertility put a strain on those affected. Klinefelter syndrome life expectancy is limited in that patients are 20 times more likely to develop breast cancer.

Patients with Klinefelter syndrome have average intelligence. Nevertheless, they often need more time to learn new things. Linguistic and motor development should be promoted early through speech therapy and occupational therapy.

Klinefelter syndrome: desire for children

In order to give Klinefelter syndrome patients the opportunity to produce children, sperm can be taken from the testes in early adolescence. At the time and before testosterone therapy, the chance of finding functioning sperm is highest. The material obtained by means of testicular biopsy is analyzed, processed and frozen (cryopreservation). So it is preserved for a long time and is available at a later desire to have children. Then the woman is taken an egg and fertilized with the sperm cells artificially.

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