Which chromosome is affected by Klinefelter syndrome

Klinefelter Syndrome

Men with Klinefelter syndrome have at least one extra chromosome. Chromosomes are the carriers of our genes - they contain, so to speak, the blueprint for our organism.

The usual set of chromosomes in humans consists of 46 chromosomes, or more precisely, 23 pairs of chromosomes. In each pair, one chromosome comes from the father and one from the mother. Two of these chromosomes (X and Y) determine a person's sex. Usually a man has chromosome set 46 XY, a woman has chromosome set 46 XX.

However, due to a specific disorder in cell division, a child can receive two sex chromosomes from one parent instead of just one. This creates a set of chromosomes with more than 46 chromosomes - in boys mostly 47 XXY (see graphic above). This particular set of chromosomes can be found either in all or only in part of the body's cells.

The genetic pattern 47 XXY occurs in one to two out of 1,000 male newborns. In Germany, around 80,000 boys and men are affected. Many probably don't even know.

What are the consequences of the extra X chromosome?

The affected men have small, firm testicles that can produce very few or no fertile sperm (azoospermia). The result is usually infertility.

The testes also produce little testosterone (male sex hormone). The hormone deficiency has various effects. Puberty can be delayed. Beard growth and pubic hair are often only slightly developed. Because the male sex hormone slows down growth, those affected are often very tall, but their body proportions are normal.

The changed hormone situation can lead to breast formation in men (gynecomastia). The sexual excitability can decrease, erection disorders occur.

Certain health problems are much more common in men with Klinefelter syndrome: for example, the so-called metabolic syndrome. This is what doctors call a combination of overweight, high blood pressure, and increased blood sugar and blood lipid levels. The risk of bone loss (osteoporosis), anemia and blood clots (thrombosis and embolism) is also increased.

Children and adolescents with Klinefelter syndrome sometimes have problems with motor skills and language development and may need targeted support in these areas.

How does the doctor diagnose Klinefelter syndrome?

A Klinefelter syndrome can be noticed during prenatal diagnostics, for example during an amniotic fluid test. Delayed puberty in childhood can indicate the syndrome. In adults, the diagnosis is often made when the extra X chromosome causes discomfort that leads them to see a doctor. These include, for example, an unfulfilled desire to have children, erectile dysfunction or osteoporosis.

The doctor examines the patient in detail. The size of the testicles and the degree of secondary body hair may already provide clues. To confirm the diagnosis, the doctor arranges a so-called karyogram - an examination of the chromosome set. For this purpose, cells (for example lymphocytes) are removed and treated in such a way that they remain in the phase of cell division. In this phase, the genetic information is packaged in the form of chromosomes. This is how they can be analyzed.

Further examinations serve to identify possible consequences of the chromosome change. This includes - depending on the case - an examination of the semen (the ejaculate), a blood count to determine an anemia, the measurement of certain hormones (LH, FSH and testosterone) in the blood, a bone density measurement and the search for diabetes, e.g. due to glucose - Stress tests.

The appearance of Klinefelter syndrome can vary widely. Specialists therefore suspect that the diagnosis remains undetected for life in around three quarters of those affected.

Treatment with testosterone

In adult men with Klinefelter syndrome, the hormonal balance can be balanced with testosterone supplements. They replace the missing endogenous hormone (so-called substitution therapy). This often increases the quality of life of those affected and has measurable positive effects on muscle mass, muscle strength and bone density. The blood count and sugar metabolism normalize, sexual excitability increases, and erectile dysfunction improves. It is important that the doctor closely monitors the therapy and adjusts it precisely to the individual needs of the patient.

The question of when to start testosterone treatment is not entirely clear. Individual observations show beneficial effects with early therapy, i.e. from around puberty. Caution is advised, however, because the hormone replacement can suppress the self-production of testosterone and the formation of semen. Without treatment, symptoms of testosterone deficiency usually appear in the third decade of life. At this point at the latest, treatment with testosterone preparations is indicated.

A testosterone depot syringe has been available for this therapy for several years. At the beginning of the treatment it has to be repeated after six weeks, after that only every three months. Another option is testosterone-containing gels that are applied daily to the skin of the abdomen and upper arms.

Which therapy is most suitable in each individual case should be discussed with the doctor on an individual basis.

Without treatment, the life expectancy of Klinefelter syndrome can be reduced - especially due to possible side effects such as diabetes or vascular diseases. In addition, men with Klinefelter syndrome have a slightly higher risk of developing breast cancer and certain germ cell tumors. Those affected are best advised by a doctor about which preventive measures make sense in each individual case.

Although the possible effects of chromosome changes cannot be explained by a testosterone deficiency alone, a carefully adjusted testosterone substitution can increase life expectancy.

Are there any further measures required?

In addition to substitution therapy, symptomatic treatment may be necessary - i.e. therapy that alleviates or remedies symptoms without eliminating their cause.

Before puberty, this often includes treatments such as speech therapy, exercise therapy, or physiotherapy.

Breast formation in men (gynecomastia) can hardly be influenced by hormone treatment. Your treatment consists in the removal of excess glandular tissue (mastectomy) by a surgeon who is experienced in this field.

Can I become a father with Klinefelter Syndrome?

Spontaneous fatherhood in men with Klinefelter syndrome cannot be ruled out, but it is extremely rare. If there is an unfulfilled desire to have children, a method of artificial insemination can help: the doctor may be able to obtain sperm from the ejaculate or, with a higher success rate, directly from the testicles in a small operation. He injects these sperm into the egg (so-called intracytoplasmic sperm injection, or ICSI for short). About half of the couples treated in this way lead to pregnancy and childbirth. Most of the children have a normal set of chromosomes. However, there is an increased risk of other chromosome changes (for example with an additional chromosome 18 or 21). Couples can best seek advice from the treating doctor.

In the case of adolescents with Klinefelter syndrome, sperm cells may also be obtained and frozen (cryopreserved) if they later wish to have children.

Consulting expert: Professor Dr. med. Dr. h.c. Eberhard Nieschlag

Professor Eberhard Nieschlag is a specialist in internal medicine, endocrinology and andrology. He was director of the Institute for Reproductive Medicine at the Münster University Hospital. His clinical and scientific focuses include the diagnosis and treatment of unwanted childlessness, hypogonadism in men (underactive testicles), delayed puberty development and hormonal complaints in aging men. Another focus is the development of methods of contraception for men.


Nieschlag E: Klinefelter syndrome: Most common form of hypogonadism, but often overlooked and untreated. In: Dtsch. Arztebl Int 2013, 110 (20): 347-53. Online: hwww.aerzteblatt.de/archiv/138479 (accessed on October 30, 2013)

Nachtigall M, Margenreiter M, Linshalm C: Guideline Klinefelter Syndrome in Journal für Urologie und Urogynäkologie 2008, 15: 22-23. Online: www.kup.at/kup/pdf/7434.pdf (accessed on October 30, 2013)

Guideline Klinefelter Syndrome and Cancer, as of December 2011. Online: www.dgho-onkopedia.de/de/onkopedia/leitlinien/klinefelter-syndrom-und-krebs (accessed on October 30, 2013)

Important NOTE:

This article contains general information only and should not be used for self-diagnosis or self-treatment. He can not substitute a visit at the doctor. Unfortunately, our experts cannot answer individual questions.