Klinefelter Syndrome

Klinefelter characteristics

What is Klinefelter Syndrome?

Klinefelter Syndrome is a common genetic disorder, caused by chromosome aneuploidy, which solely affects males. Klinefelter’s  is the product of chromosomes not separating correctly during meiosis in either the testes or the ovaries. The product of nondisjunction leaves the Klinefelter male with a genotype of 47:XXY. Men who have Klinefelter’s typically have male external features despite having two X chromosomes. This is due to the Y chromosome being present and the SRY gene will be activated, which triggers the release of the Testes Determining Factor hormone (TDF).

How does Klinefelter Syndrome occur?

Nondisjunction producing Klinefelter Syndrome

Klinefelter’s is the result of nondisjunction, the failure of homologous chromosomes to separate, during meiosis. Due to this error a male will inherit at least one extra X-chromosome. Typically, males who have Klinefelter’s are 47:XXY, but there have been cases of 48:XXXY, 49:XXXXY, or 48:XXYY.

The more the genotype deviates from the standard 46:XY, the severity of the condition increases. The cause of Klinefelter Syndrome is presently unknown. Scientists have discovered the likelihood of being born with Klinefelter’s is not correlated with old age like Trisomy 21, and the extra chromosome is inherited from both males and females with equal frequency.

Common Traits

There are multiple traits common to Klinefelter’s

Male with Klinefelters Syndrome

  • Small external genitalia and testes
  • Breast development (gynecomastia)
  • Sterility (in most cases)
  • Reduced facial and pubic hair
  • Normal intelligence*
  • Above average height.
  • Presence of Barr Bodies

The severity of these conditions increases the more the standard 46:XY genotype deviates.

*It should be noted that most males who have Klinefelter’s are intelligent by society’s standards, but most suffer from: cognitive deficiencies, difficulty speaking, and memory loss.

And at a rate of 1/600 males born with this condition, it is one of the more common sexual, genetic disorders.

Sexual Development

When the SRY gene is activated, it will trigger Testes Determing Factor, TDF, which will develop seminiferous tubules, Sertoli cells, and Leydig cells. The Sertoli cells will release Müllerian-inhibiting Substance, MIS, which inhibits the development of a cervix, uterus, and vagina.

While the Klinefelter male will exhibit masculine traits, his serum testosterone level will be low. This produces femnizing effects such as gynecomastia (male breast development), hypogonadism, and a lack of both pubic and body hair.

Strangely, despite the low levels of serum testosterone, the Klinefelter male will have high levels of FSH and LH despite the low level of serum testosterone. Consequently, he will fail to fully develop secondary sexual characteristics such as body hair, pubic hair and external genitalia.

Fetal Testing

Picture of a CVS

To test for Klinefelter’s prenatally, parents can perform a Chorionic Villus Sampling (CVS) test or by Amniocentesis

Amniocentesis is a fetal scanning method that is performed around week 14 to 16. A needle is inserted into the uterine wall and an amniotic fluid puncture is performed in order to gather the amniotic fluid. These cells can also then be karyotyped and analyzed in order to determine the child’s genotype.

Chorionic cells are removed from the placenta by a catheter that is guided by an ultrasound. These cells can also then be karyotyped and analyzed in order to determine the child’s genotype. This is can be performed around week five, but it is usually done around week 8 to 10. Due to its invasive nature, it can cause miscarriage. The advantage of using CVS is that it can performed earlier than amniocentesis, but it is the more dangerous of the two prenatal tests.

The benefits of performing both tests is that they can identify as many as 40 genetic abnormalities.

Some of these abnormalities include:

  • Klinefelter Syndrome
  • Trisomy 21
  • Prader-Willi Syndrome
  • Parkinson’s Disease
  • Huntington’s Disease
  • Cystic Fibrosis

In the past, both amniocentesis and CVS weren’t performed with frequency – they were performed if there was a history of disease in the family or if the female was 40 or over. Now, both procedures are quickly becoming the norm for the health of the fetus, the liability of the doctor, and as a requirement for coverage from insurance companies.

Testing After Birth

Karyotype of a male with Klinefelter

The trouble with diagnosing Klinefelter Syndrome after birth is the symptoms are ambiguous. Diagnoses are typically made: before birth, shortly after birth, early childhood, or during in adulthood (typically when the Klinefelter is being tested for infertility). In addition to testing for infertility, a physician will likely order a test for high levels of gonadotropins, which are typically high in Klinefelter males.

During childhood and into adulthood, if one suspects he or a loved one suffers from Klinefelter Syndrome, a way to test called a karyotype can be performed.

Certain actively dividing cells, such as bone marrow or white blood cells, are displayed as a picture of chromosomes entering into metaphase – they need to be prevented from undergoing anaphase.

The cells for karyotyping are spread onto a microscopic slide, stained with special dye, and photographed.  This test is especially useful in figuring out if a male is sterile, and used as a confirmatory test for Klinefelter Syndrome.

There are incidents of men finding out they have Klinefelter by the presence of Barr bodies. Barr bodies are darkly staining, inactive X chromosomes. Barr bodies occur in order to limit the amount of gene product two X-linked genes would produce, which helps keep the protein concentration between males and females equal. Therefore, a typical male has zero Barr bodies and females have one.


Testosterone Molecule

Klinefelter Syndrome is irreversible, and its effects are permanent. The effects can be minimized; however, with testosterone therapy.

This treatment typically starts in adolescence and required the teenager to get an testosterone every two weeks; in the form of a skin patch or injection.

Increases in testosterone can produce the following

  • Increased body hair, pubic hair, and facial hair.
  • Increased muscle development
  • Increased sex drive
  • Reduction or prevention of gynecomastia (male breasts)
  • Increased self esteem

The sides effects of Testosterone therapy are uncommon but include:

  • Behavioral problems
  • Increases in acne
  • Rapid sexual development

Psychology and Behavioral Effects

Psychological treatment can benefit the Klinefelter teenager by increasing their confidence as well as helping with him with his learning disabilities.

If a Klinefelter male decides to undergo testosterone therapy, it is not clear if psychological changes are a result of the treatment or a byproduct as masculinity and confidence increase.

One study found that men 27-37 are likely to be depressed, lack energy and enthusiasm, and are prone to fits of anger. This study also showed that by the time these men reach their 40s, these problems are conquered.

A Man Describes His Life With Klinefelter Syndrome


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