Course:MEDG550/Student Activities/Kleinfelter Syndrome

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Klinefelter syndrome is a genetic condition in which a male is born with an extra copy of the X chromosome, resulting in 3 copies of the sex chromosomes (XXY) instead of the typical 2 copies that are seen (XY). This extra X chromosome results in decreased testicular function and decreased testosterone production - the sex hormone that promotes male sexual development before birth and during puberty. Klinefelter syndrome is characterized by reduced muscle mass, increased breast tissue, small testicles, infertility and reduced body/facial hair. A relatively common condition affecting 1 in 500 to 1 in 1,000,[1] it often goes undiagnosed as the symptoms are mild and vary from person to person – not every man with Klinefelter syndrome will present with the same features.

Clinical Features

Cartoon representation of the clinical symptoms of Klinefelter syndrome.

Men with Klinefelter syndrome vary in their features, and may have any or all of the following:

  • Small testes
  • Decreased testosterone, resulting in:
    • Delayed puberty
    • Breast enlargement (gynecomastia)
    • Infertility
  • Genital differences
    • Undescended testicles (cryptorchidism)
    • Opening of the urethra on the underside of the penis (hypospadias)
    • Unusually small penis (micropenis)
  • Children and adults taller than peers
  • Increased risk of breast cancer compared to XY males


Can be detected through a karyotype - simple blood test.

Klinefelter syndrome variants

Something about how there is XXXY, XXXXY - additional X chromosomes that intensify & give a more severe phenotype.


Mild, many men do not know until later on by fluke. If you know before puberty, can supplement with testosterone - virility?

Resources and Support


Human DNA is condensed and packaged into structures called chromosomes; along each chromosome are smaller segments called genes that give our body instructions for making different proteins essential for everyday life. Normally, every cell in our body contains 23 pairs of each chromosome - one of each pair coming from mom, the other from dad. 22 of these chromosomes pairs are shared between men and women, but the fundamental difference between men and women lies in the 23rd pair of chromosomes, termed the sex chromosomes. Male sex is defined by the presence of one X and one Y chromosome, while females have two X's. Men affected with Klinefelter syndrome have a an extra copy of the X chromosome, which is responsible for their clinical features.

An artistic depiction of a karyotype of a man with Klinefelter syndrome. There are 22 pairs of autosomes present, but 3 sex chromosomes (XXY, circled)

The presence of the extra X chromosome occurs by chance through a process called non-disjunction. During maturation and development, sperm and egg cells (gametes) undergo a series of divisions (meiosis) that ends with each gamete having only one copy of each chromosome (23 total chromosomes). Thus, upon the union of one egg and one sperm, the resulting embryo will have 2 copies of each chromosome - a complete set. However, random errors during these divisions (non-disjunction) can cause unequal distribution of chromosomes to sperm and egg cells. Klinefelter syndrome is caused by an extra sex chromosome in a parent's egg or sperm (XX or XY) which then gains another sex chromosome (Y or X, respectively) during fertilization, resulting in an embryo that is XXY.

Genetic Counselling


Non-disjunction is a sporadic, random event that causes Klinefelter syndrome and is therefore not inherited; if you have one child with Klinefelter syndrome, your risk for having another child with the condition is not increased above the baseline population risk. Men with Klinefelter syndrome who wish to father children through assisted reproductive technology are not at increased risk of producing sperm with extra copies of the sex chromosomes[2].

Infertility and Assisted Reproductive Technology

Achieving a pregnancy was previously not thought possible in many men with Klinefelter syndrome, as these men do not have sperm in their semen (azoospermia). However, through assisted reproductive technology, doctors can find sperm by means of microsurgical testicular sperm extraction (TESE). This involves taking a microscopic testicular biopsy near the site of sperm production; if a man's sperm can be extracted from this biopsy, the sperm can be used to fertilize his partner's eggs in a procedure called in vitro fertilization with intracytoplasmic sperm injection (IVF with ICSI). Because the sperm have not yet fully matured, they do not move efficiently (immotile) and are incapable of fertilizing an egg on their own. ICSI therefore allows for the direct injection of a sperm into an egg extracted from the mother, which can then grow, mature and ultimately be implanted into the mother.


  1. Genetics Home Reference, 2013
  2. Bergère M, Wainer R, Nataf V, et al. Biopsied testis cells of four 47,XXY patients: fluorescence in‐situ hybridization and ICSI results. Hum Reprod. 2002;17:32‐37