Klinefelter Syndrome Latest Facts: Symptoms, Diagnosis and Treatment

What is Klinefelter Syndrome?

Klinefelter Syndrome is a genetic disorder resulting from an extra X chromosome in males; therefore this condition is also called 47, XXY. This condition is characterized by infertility and the presence of feminine features in affected males. The condition was named Klinefelter Syndrome in honor of Americal endocrinologist Harry Klinefelter, who was the first to describe this condition in 1942.

Male With Klinefelter Syndrome

Male With Klinefelter Syndrome. Image courtesy of Malcolm Gin.

The severity of Klinefelter Syndrome increases with the number of extra X chromosomes i.e., 48XXXY syndrome or 49XXXXY syndrome. More than half of Klinefelter syndrome embryos eventually undergo a miscarriage and never get born.

The frequency of this condition is one in every 1000 live male births, but this number may be higher as it is believed that up to 75% of Klinefelter syndrome cases go undiagnosed throughout their life. In fact, about 3% of all infertility cases in males are due to Klinefelter Syndrome, and it is also the most common cause of hypogonadism in males.

What Causes Klinefelter Syndrome?

Advanced maternal age, i.e. becoming a mother at an age older than 40 is the only proven risk factor for Klinefelter Syndrome. Women who give birth to a child when they are above 40 have four times more likelihood of having a child with Klinefelter syndrome than women who give birth at age 24.

During cell division, homologous chromosomes separate and form daughter chromosomes. But if they fail to separate during meiosis or mitosis, this can result in nondisjunction disorders such as monosomy or trisomy. Trisomy disorders are the most common chromosomal disorders including Down syndrome and Klinefelter syndrome.

Normally, the sperm and egg only contain one sex chromosome, which then conjugates with each other to form XX or XY. In Klinefelter syndrome, there is a failure of separation in either the two X chromosomes or the X and Y chromosome, which results in either a sperm or an egg with two sex chromosomes, XX or XY. Thus, if fertilization occurs in an egg or sperm with two sex chromosomes, the embryo will contain an extra X chromosome.

Symptoms and Signs

Klinefelter Syndrome predominantly affects the reproductive system in males, causing hypogonadism, infertility, and low libido. A child with Klinefelter syndrome presents with muscular weakness, but as the child nears adulthood they tend to have a tall stature. Children with this condition may present with difficulties in learning languages, and performing executive functions but these cognitive issues can often be managed with timely cognitive and behavioral therapy.

In many cases, symptoms are often mild and can go unnoticed throughout the patient’s life. Although this occurs less often, there can be severe forms of Klinefelter Syndrome, in which case the patient presents with obvious symptoms such as gynecomastia, female pattern pubic hair, less body hair, decreased libido, tall stature, and weak muscles.

Hypogonadism is a common presentation and results in decreased serum levels of testosterone, but in contrast, there are higher levels of follicle-stimulating hormone and luteinizing hormone. Affected males have a smaller than average testicular size, and are often less than 2 cm in size.

The extra X chromosome also predisposes affected males to certain pathological conditions such as breast cancer, deep venous thrombosis, autoimmune diseases, and pathological fractures due to osteoporosis.

Klinefelter Syndrome

Klinefelter Syndrome


In patients with a high degree of suspicion due to the presence of characteristic physical features of Klinefelter syndrome such as tall height, gynecomastia, microorchidism, and low body hair, a confirmatory diagnostic test is essential. Apart from the physical features, lower than normal levels of testosterone with elevated levels of luteinizing hormone and follicle-stimulating hormone are also indicators of Klinefelter syndrome.

Due to the variable nature of clinical presentation in patients with Klinefelter syndrome, any patient suspected of having this condition should undergo a diagnostic test. As with other chromosomal disorders, karyotyping is the standard diagnostic method for Klinefelter Syndrome. To confirm the diagnosis in children, a blood sample is obtained to karyotype the chromosomes on lymphocytes.

Treatment of Klinefelter Syndrome

Klinefelter Syndrome is a genetic mutation, and hence it has no cure but certain pharmacological therapies can be used to treat the clinical manifestations of this disorder.

A major concern in patients with Klinefelter syndrome is infertility in men, and although there are no methods available to reverse this, reproduction can still be achieved by directly extracting the sperm from the testis. The extracted sperm can then be inoculated into an egg to induce fertilization. There are documented reports of hundreds of successful reproduction from males with Klinefelter syndrome using IVF.

The prognosis for Klinefelter Syndrome

Life expectancy in patients with Klinefelter syndrome is near to the average life expectancy and therefore has an overall good prognosis. Males with Klinefelter Syndrome who wish to reproduce can often successfully do so using In-vitro Fertilization techniques. Other more serious conditions associated with Klinefelter Syndrome such as breast cancer and deep venous thrombosis can be managed with regular screening and early intervention.





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    • Sony Sherpa MD Sony Sherpa MD


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