Klinefelter Syndrome is a genetic disorder that affects males, characterized by the presence of an extra X chromosome in their cells. This genetic defect can affect the development of the testicles, resulting in less production of the male hormone testosterone. Men with this syndrome also have fertility problems, and it can sometimes be associated with language problems and learning difficulties. In this article, we willDalili Medical discuss Klinefelter Syndrome and its impact on fertility.

What is Klinefelter Syndrome (XXY Syndrome)?

 

Klinefelter Syndrome is a genetic disorder that affects males, characterized by the presence of an extra X chromosome in the body’s cells. This affects the normal physical structure of males and their hormonal activity. This syndrome is one of the main causes of male infertility and difficulty in conceiving naturally, and it can also affect social life and the nature of relationships that an individual builds. Klinefelter syndrome results from the presence of an extra copy of the X chromosome, and is often not diagnosed until adulthood. This syndrome can negatively affect the development of the testicles, causing them to be smaller than normal and decreased production of testosterone. The condition can also lead to increased breast tissue, decreased body and facial hair, and decreased muscle mass. It is worth noting that symptoms and consequences vary from person to person. While most men with Klinefelter syndrome produce little or no sperm, some may be able to father children with the help of assisted reproductive technologies.

**At what age is Klinefelter syndrome diagnosed?**

 

Klinefelter syndrome is usually diagnosed during adulthood, when some symptoms appear, such as abnormal testicle development. However, this syndrome can also be diagnosed through prenatal genetic testing.

**Can a person with Klinefelter syndrome have children?**

 

People with Klinefelter syndrome have difficulty conceiving, with most cases being infertile due to low or no sperm production. However, there are several methods of reproduction that can be used to overcome this problem.

**How ​​long does a person with Klinefelter syndrome live?**

 

Men with Klinefelter syndrome live a normal lifespan, but their health may be affected by potential diseases. Research suggests that people with the condition live an average of one to two years less than men without the condition.

**XXY syndrome occurs in three different forms in men:**

- The most common form of XXY syndrome involves an extra X chromosome in all of the body's cells.

- Mosaic Klinefelter syndrome.

How is this condition studied in men?

 

This syndrome is usually diagnosed in adolescence or adulthood, or when trying to conceive, unless the child has problems early on that require genetic karyotyping testing.

The karyotyping test is a method that allows us to diagnose a patient as a carrier of the 46+XXY chromosome disorder.

Furthermore, a comprehensive assessment by a male specialist requires a complete study of the hormonal composition and a physical examination, in order to assess the ability to reproduce and the general health status.

Can Klinefelter syndrome be prevented?

 

Unfortunately, Klinefelter syndrome is a condition that is difficult to prevent, as it occurs in the genetic code before birth. This condition is not hereditary, and parents cannot take any measures to prevent it for their child.

What are the solutions available for Klinefelter syndrome?

 

Klinefelter syndrome, characterized by the karyotype 47+XXY, was previously associated with complete infertility in men. However, we are constantly working in our group to develop treatment paths aimed at enabling biological reproduction for males suffering from this syndrome, in addition to providing medical consultations to treat any other abnormalities or disorders they may encounter.

There are cases in which pure cells carrying genetic changes are present alongside normal cells, a condition known as genetic mosaicism. In these patients, isolated sperm can be found either in the semen or in the tissues. Therefore, after a detailed study of the urinary tract, it is necessary to search directly in the testicle by taking a biopsy.

If the probability of finding sperm is low, the couple can choose to use sperm from an anonymous donor bank as an available alternative, provided that this is within their options.

**Klinefelter Syndrome and ICSI**

People with Klinefelter Syndrome suffer from infertility, due to the weakness of the testicles in producing testosterone and sperm. Therefore, doctors resort to using modern techniques, the most prominent of which is the ICSI technique. The ICSI technique helps couples who are facing difficulties in conceiving, as the process involves withdrawing eggs from the woman and injecting them with sperm from the man, and this process is done in the laboratory outside the mother's womb. After the egg is fertilized, it is transferred to the lining of the uterus for implantation. Some symptoms may appear on the woman indicating the success of the IVF process and the occurrence of pregnancy, the most prominent of which are:

- Pelvic cramps.

- Breast pain.

- Vaginal bleeding.

- Nausea.

- Feeling tired and exhausted.

**Risks and health problems of Klinefelter syndrome**

The majority of men with Klinefelter syndrome do not suffer from life-threatening health problems, but they may have some potential health risks.

**Infertility and infertility:** This problem is considered the main one in patients, and is due to several factors, including low levels of testosterone, in addition to abnormalities in sperm that affect their ability to fertilize. However, there are some treatments available that can help overcome this problem, such as artificial insemination or injectionSperm directly into the eggs.

**Type 2 diabetes:** Patients suffer from a mild degree of disturbances in the level of fasting blood glucose (high blood sugar before eating), which increases their risk of developing type 2 diabetes, known as non-insulin-dependent diabetes.

**Bone density loss and osteoporosis:** This occurs as a result of low levels of testosterone, which plays an important role in protecting bones from fragility, making them weaker and more susceptible to fracture.

**Cardiovascular disease and thrombosis:** The incidence of cardiovascular disease is slightly higher compared to healthy people, due to the increased tendency of the blood to clot.

**Autoimmune diseases:** This group of diseases includes conditions in which immune cells recognize the components of the body as foreign bodies and attack them. Examples of these diseases include systemic lupus erythematosus (SLE).

Hypothyroidism: refers to the weakness of the thyroid gland and the low levels of thyroid hormones produced, which leads to a feeling of lethargy, fatigue, general weakness, and slow heart rate, in addition to other problems resulting from the decrease in the body's metabolic rate.

Psychological problems: include disorders such as anxiety and depression.

Breast cancer in males: The likelihood of developing breast cancer is higher in males with Klinefelter syndrome compared to other males, but this condition remains rare compared to females.

In general, these disorders can be treated when they appear, and replacing testosterone deficiency may help reduce the likelihood of developing them.

** Symptoms of Klinefelter syndrome according to their site of effect **

 

The symptoms of Klinefelter syndrome can be classified according to their site of effect and nature as follows:

** Physical symptoms ** The nature and severity of these symptoms vary based on the level of testosterone in the body, which may vary in the patient himself with age. Among these symptoms are:

- Smaller size of the testicles, and they may sometimes shrink after puberty.

- Gynecomastia, which may accompany the patient throughout his life and sometimes requires surgical intervention to treat it, due to a lack of testosterone and increased production of estrogen from the testicles in some patients.

- Lack of facial and body hair in patients who do not receive testosterone treatment to compensate for its deficiency, while some patients with Klinefelter syndrome may suffer from an increase in body hair without using testosterone.

- Feeling tired and generally fatigued, especially with decreased muscle mass and bone density.

- Lack of coordination of movements while walking or running.

- Lack of body shape, characterized by long arms and legs and a short trunk, in addition to a wide pelvis with a narrow distance between the shoulders.

**Cognitive symptoms and learning problems**Klinefelter syndrome does not lead to a decrease in patients' intelligence quotient (IQ), as they achieve good results in schools and universities. However, they face challenges in the areas of cognition, emotional intelligence and creativity, and these challenges appear as follows:

- Delayed speech during childhood, difficulty in distinguishing between phonetically similar words, in addition to difficulty in pronouncing words clearly.

- Difficulty in expressing feelings, needs and ideas through speech, and forgetting some words associated with the names of things or people.

- Difficulty in analyzing what the patient hears from others, which requires some time to understand what is being said or to absorb the feelings of the speaker.

- Dyslexia, which requires the patient to take more time to understand the texts he reads.

- Weakness in communicating with others, which leads to difficulties in social relationships due to challenges related to speech, self-expression and feelings.

- Difficulty in performing executive tasks, which include organizing, planning, following up on achievement and setting goals.

- Easily distracted by the simplest sounds and movements, even the texture of some clothes may be an obstacle to the patient's concentration.

**Causes**

A person's body cells have 46 chromosomes, or 23 pairs, at birth, including the X and Y sex chromosomes.

People born female have two X chromosomes, forming the XX combination, giving them sex characteristics such as breasts and a uterus.

People born male have one X chromosome and one Y chromosome, forming the XY combination, giving them sex characteristics such as a penis and testicles.

People with Klinefelter syndrome are born with an extra X chromosome, resulting in an XXY combination in their cells. This happens randomly during pregnancy, with the extra chromosome usually starting in the mother's egg in about 50% of cases, and originating from the father's sperm in about 50% of cases.

Some people with the condition may have several extra X chromosomes, and their chromosome combinations may include the following: XXXXY. Others have chromosomal abnormalities in different cells, where some cells may be XY and others XXY, which is known as mosaicism.

**Diagnosis of Klinefelter Syndrome**

A thorough physical examination is performed on individuals with Klinefelter Syndrome. Diagnostic procedures include using a karyotype or cheek swab test to confirm the presence of the extra X chromosome. Diagnostic tests are necessary to verify the clinical analysis. Both a buccal smear test and a karyotype analysis can confirm a diagnosis of Klinefelter Syndrome.

**Hormonal Testing**: This aims to measure the abnormal hormone levels associated with XXY syndrome, and is done through a blood sample. The hormones tested include estradiol, follicle-stimulating hormone, luteinizing hormone, and testosterone.

**Chromosome Analysis/Karitotype**: Also known as karyotyping, XXY status is determined by measuring the number of chromosomes using specific techniques on a blood sample or buccal smear.

**Semen analysis**: Used to evaluate fertility and measure the quantity of sperm.The quality of the patient's semen. Also known as sperm count, this test is performed by a fertility specialist.

**Prenatal Diagnosis:** As part of the prenatal diagnosis, women who are over 35 years of age or who have a family history of genetic conditions may be at a higher risk of developing Klinefelter Syndrome (KS).

**Chorionic Villus Sampling:** A diagnostic test is performed on pregnant women between 11 and 13 weeks of pregnancy to detect any genetic disorders. This procedure involves inserting a small needle into the woman's abdomen and uterus to collect a sample of chorionic villi, which can be analyzed to detect any chromosomal abnormalities.

**Amniocentesis:** Amniocentesis is performed between 15 and 18 weeks of pregnancy. This procedure involves extracting amniotic fluid from the amniotic sac using a small needle. The amniotic fluid protects the fetus and contains fetal cells that can be used to examine the chromosomes.

**Fertility tests**: Klinefelter syndrome often goes undetected until a person undergoes fertility tests and analyses, as infertility is one of the most common complaints that prompt men with this syndrome to visit a doctor.

**Sex hormone levels test**: If the doctor suspects the presence of this syndrome, the patient may be asked to undergo a blood test to measure the level of testosterone, or sometimes the levels of these hormones may be measured in a urine sample.

**Karyotype test**: This test is used to confirm the diagnosis, as the patient's cells are examined under a light microscope to study the shape and number of chromosomes, and the diagnosis is confirmed when an extra X chromosome is observed.

**Amniotic fluid cell analysis**: Sometimes, Klinefelter syndrome can be diagnosed before the baby is born, by taking a sample of the amniotic fluid surrounding the fetus in the uterus, and studying its cells, where the extra X chromosome appears.

**Treatment**

Klinefelter syndrome causes abnormalities in the sex chromosomes, and there is no specific treatment for it yet. However, treatments can help reduce the consequences, especially if started early. Here are some possible treatments.

**Drug therapy**Klinefelter patients suffer from a deficiency in testosterone, an essential male hormone that contributes to maturation and activation of the testicles to produce sperm, which affects reproductive capacity. Drug therapy using certain medications can contribute to increasing testosterone levels, which improves the patient's health condition by:

- Enhancing muscle mass.

- Increasing voice roughness.

- Increasing sexual desire.

- Improving focus and attention.

- Maturing the reproductive organs.

- Strengthening bones and preventing fractures.

- Promoting the growth of facial hair and other body parts.

- Giving the person a masculine appearance, which reduces his feelings of anxiety and stress.

It is important to note that hormonal therapy does not increase the size of the testicles, nor does it treat gynecomastia, nor is it a final solution to the infertility that Klinefelter patients suffer from. There are other ways to treat infertility that we will learn about later.

**Cognitive behavioral therapy** Patients with Klinefelter syndrome may need to consult a psychologist to improve their social relationships and overcome the psychological problems they may face. This can help them achieve a normal life free from anxiety and low self-confidence. However, not all patients need this type of treatment.

**Infertility treatment:** Most men with Klinefelter syndrome have difficulty conceiving, due to the inability of the testicles to produce semen or a low sperm count. Therefore, the chances of conceiving naturally from a man with this syndrome are slim. However, assisted reproductive technology, such as in vitro fertilization, may provide solutions for some cases of infertility, where sperm are extracted from the testicles and injected into the cytoplasm of the egg.

**Testosterone replacement therapy:**Because men with Klinefelter syndrome do not produce enough testosterone, starting testosterone replacement therapy early in puberty can help boys achieve the physical changes associated with puberty, such as deepening of the voice, development of facial and body hair, and increased muscle mass and penis size. Although testosterone replacement medications do not treat infertility, they may help increase bone density and reduce the risk of fractures. Testosterone can be given by injection or by using a gel or skin patch.

**Fertility treatments**: Men with low sperm production may benefit from intracytoplasmic sperm injection (ICSI), which involves extracting sperm from the testicle and injecting them directly into a woman’s egg.

**Breast tissue removal**: For men with enlarged breasts, cosmetic surgery may be performed to remove excess tissue.

**Educational support**: Teachers, school counselors, or nurses can help provide additional educational support.

**Speech therapy and physical therapy**: can help overcome physical weakness, speech and language problems.

**Psychological counseling**: Counseling, whether from a family therapist, psychologist or counselor, can help people with Klinefelter syndrome deal with the emotional problems associated with puberty, adolescence and infertility.

How can infertility be treated in Klinefelter syndrome?

 

The relationship between Klinefelter syndrome and marriage is clear, as patients with this syndrome suffer from a lack of sperm in the semen due to a deficiency in testicular activity. In this case, infertility treatment begins with testicular activation and increasing the level of testosterone through drug therapy, which helps improve sperm production relatively.

AfterAfter completing the testicular activation stage, a microscopic examination of the testicle is performed to extract sperm, followed by the ICSI procedure. Here are the details of these steps:

**Pharmacological testicular activation**Pharmacological or hormonal activation of the testicle is the first step followed by the male doctor with Klinefelter cases, with the aim of increasing the secretion of testosterone and stimulating sperm production. Among the medications used in this context:

- Human chorionic gonadotropin (hCG).

- Estrogen receptor modulators, such as: Tamoxifen.

- Aromatase inhibitors, such as: Anastrazole.

In addition to antioxidants that contribute to improving the quality of sperm produced inside the testicle, this enhances the chances of success of the ICSI procedure in the future. However, testicular activation must be done under the supervision of a male specialist, while adhering to the drug doses he specifies and conducting the necessary tests to assess the extent of improvement. It is also recommended to perform an anti-Mullerian hormone (AMH) test, which detects the level of activity of the seminiferous tubules inside the testicle, which is important to determine the likelihood of success of the microscopic examination and the chances of finding sperm.

**Micro-TESE** Micro-TESE is a very effective method for sperm extraction, as it has fewer complications compared to other extraction methods, and it also achieves higher success rates. This procedure is performed using a high-magnification surgical microscope, which ensures reduced surgical intervention.

Using German technology and the Carl Zeiss microscope, a comprehensive examination of the testicle can be performed, which increases the chances of success compared to traditional techniques.

**ICSI in Klinefelter Syndrome** After extracting sperm from the testicle, ICSI is considered the final stage in treating Klinefelter infertility. The sperm are prepared in the laboratory, the best quality is selected, and then the sperm is injected into the egg after extracting it from the wife's ovary. After that, the fertilized egg grows to a certain stage, then is implanted in the lining of the uterus to complete its development into a full-fledged fetus. It is important to note that the success rate of infertility treatment for Klinefelter patients has gradually increased with the advancement of medical technologies, as the rates of successful pregnancy in these cases have reached about 43% according to the latest medical studies, provided that the treatment procedures, starting with testicular activation, are carried out under the medical supervision of a highly experienced andrologist.

**Coping with the disease and support** If you suffer from Klinefelter syndrome, you may find it useful to follow some of the following care methods: Maintain continuous communication with your doctor, as appropriate treatment can help maintain your physical and psychological health, as well as prevent future problems such as osteoporosis. Discuss with your doctor your plans for you and your partner to start a family. It is also advisable to communicate with other people who face the same challenges, which helps you learn how to deal with your condition better.