What is Klinefelter syndrome?

Klinefelter syndrome is a genetic condition, resulting in an extra copy of the X chromosome.  Biologically male individuals have one X and one Y chromosome, and biologically female individuals have 2 X chromosomes.  A chromosome is a DNA molecule consisting of part or all of the genetic information of an organism.  This condition is also known as XXY aneuploidy.

Klinefelter syndrome is the most common human sex chromosome disorder and affects 1 in every 500-600 males in the United States.  Mentally challenged males are 5-20 times more at risk developing this condition than the general population.  This condition affects only males and is often detected in adulthood.  The main signs and symptoms which are going to raise the suspicion of Klinefelter syndrome are due to a reduce functionality of the testes (gonads) and include infertility, erectile dysfunction (inability to get or maintain an erection firm enough to have sexual intercourse) and a decrease in body or facial hair growth.

What causes Klinefelter syndrome?

Klinefelter syndrome is a genetic condition that occurs when there is a random error, causing a male to be born with an extra X chromosome.  The human body normally have 46 chromosome or 23 pairs of chromosomes, including 2 sex chromosomes which determines the person’s sex.  Males have an X and a Y sex chromosome (XY) and females have 2 X sex chromosomes (XX).

The most common cause of Klinefelter syndrome is when there is an extra copy of the X chromosome (XXY).  In addition, in certain cases, the extra X chromosome are only in some cells and this variation is called mosaic Klinefelter syndrome.  In rare cases, more than one extra copy of the X chromosome is acquired which results in a more severe form of the condition.

What are the signs and symptoms of Klinefelter syndrome?

The signs and symptoms of Klinefelter syndrome varies with age and may not present the same way in every males.  In many cases, it remains undiagnosed until adulthood or may never be diagnosed.

In babies, the signs and symptoms of Klinefelter syndrome include:

·         A delay in speaking.

·         Undescended testes at birth.

·         Delay to sit up, crawl and walk (slow motor development).

·         Weak muscles

In children under the age of 20, the signs and symptoms of Klinefelter syndrome include:

·         Enlargement of the breast tissues (Gynaecomastia).

·         Weak bones.

·         Taller than peers.

·         Broader hips, shorter torso and longer legs compared to other males.

·         Delayed, incomplete or absent puberty.

·         Small penis.

·         Small and firm testes.

·         Less muscle mass than peers.

·         Less facial and body hair compared to other boys.

·         Shy and sensitive.

·         Problems with math, writing, spelling or reading.

·         Difficulty to express themselves

·         Difficulty to make friends and socialize.

In men, the signs and symptoms of Klinefelter syndrome include:

·         Low libido (sex drive).

·         Small penis and testes.

·         Weak bones.

·         Low sperm count or no sperm.

·         Decreased body or facial hair.

·         Enlargement of the breast tissue.

·         Taller than most men.

·         Less muscular mass than other men.

Making a diagnosis

To make a diagnosis, your doctor will first take a detailed history from you to know more about your symptoms.  This condition is often diagnosed when the person reports having trouble to have children.  After the history taking, your doctor will perform a thorough physical examination to look for signs of Klinefelter syndrome.  To confirm the diagnosis, your order will order some tests and these include:

·         Androgen receptor gene quantitative real-time polymerase chain reaction (AR-qPCR) technique: This test is a simple and reliable screening tool for the diagnosis of Klinefelter syndrome.

·         Gonadal function: Klinefelter syndrome is associated with hypogonadism (impaired function of the gonads) due to an impaired response of the gonads to follicle-stimulating hormone (FSH) and luteinizing hormone (LH).  This will in turn result in a lack of sex steroid production.

·         Hormonal testing: The hormone levels measured for the diagnosis of Klinefelter syndrome include FSH, LH, testosterone, prolactin, estradiol and insulin-like growth factor (IGF-1)

·         Routine bone density scanning: The density of the bones are assessed as a deficiency in androgens (an example include testosterone) increases the risk of osteoporosis (a condition where the body loses too much bone, produces too little bone or both.

·         Measurement of the blood clotting factors: These tests are done as people with Klinefelter syndrome are at an increased risk of developing deep vein thrombosis (DVT is the formation of a blood clot within the deep veins of the legs) and pulmonary embolism (this condition occurs when a blood clot formed elsewhere gets lodged into the lungs which could be deadly) due to a hypercoagulability state (a state favourable for excessive blood clot formation).

What are the treatments of Klinefelter syndrome?

The treatments of klinefelter syndrome include:

·         Testosterone replacement therapy: This therapy is usually given at the time of puberty to help stimulate changes that usually happens during puberty such as developing a deeper voice, increasing sexual desire (libido) and muscle mass, and growing facial and body hair. This therapy is also useful in improving your bone density to reduce the risk of fractures.  However, it will not cure infertility.

·         Fertility treatment: Unfortunately, most men with this condition are typically unable to father children due to few or no sperm production in the testes. However, men who have little sperm production, intracytoplasmic sperm injection (ICSI) can be perform which involves your doctor removing the sperm directly from the testicle using a needle, into the egg.

·         Breast tissue removal: Excess breast tissue can be removed by a plastic surgeon in people with gynaecomastia.

·         Physical and speech therapy: These therapies can help people with Klinefelter syndrome who have trouble with speech or muscle weakness.

·         Psychological counselling:  The emotional issues associated with Klinefelter syndrome can be quiet challenging and therefore psychological counselling can help to teach you how to cope with them.

What are the complications of Klinefelter syndrome?

The complications of Klinefelter syndrome include:

·         Infertility.

·         Depression.

·         Anxiety.

·         Erectile dysfunction.

·         Emotional immaturity and impulsiveness.

·         Osteoporosis (weak bones).

·         Heart disease.

·         Lung disease.

·         Breast cancer.

·         Hypertension.

·         High cholesterol level.

Expectations (prognosis)

Klinefelter syndrome is a condition that affects only.  It causes many signs and symptoms that may affect your morale, self-esteem and health.  However, seeking medical advice early can help you to develop your body during puberty and live a normal life.  However, the treatment may not treat the infertility problem.

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Matsumoto, A., 2021. Clinical features, diagnosis, and management of Klinefelter syndrome.