Klinefelter Syndrome in Cats

What is Klinefelter syndrome?

Also known as XXY syndrome, Klinefelter syndrome (KS) is a sex chromosome condition that occurs when a male kitten is born with an extra X chromosome. Klinefelter syndrome is a type of trisomy, which is a chromosomal condition characterised by an additional chromosome. Down syndrome is the most well-known trisomy in humans that is caused by a third copy of chromosome 21.

Klinefelter syndrome was first described by Dr Harry Klinefelter in 1941, who examined an 18-year-old male who had gynecomastia (breast tissue),  small testicles, and no facial hair. His penis size and voice were normal for a male. Hormone therapy failed to produce any notable results either way. Eight additional patients with similar symptoms were encountered, with a range of clinical signs including low intelligence, high-pitched voices, gynecomastia and sterility.

Dr Klinefelter and his boss, Dr Albright published a paper in the Journal of Clinical Endocrinology in 1942, which describes the following.

This is actually another of Dr Albright’s diseases. He unselfishly allowed my name to come first in the list of authors; because of the length of the title [“Syndrome characterized by gynecomastia, spermatogenesis without a-leydigism and increased excretion of follicle-stimulating hormone’] and the convenience of the eponym, it became known as Klinefelter’s syndrome.

Counting chromosomes

Advances in cytological techniques enabled Joe Hin Tjio and Albert Levan to determine the correct human chromosome count was 46, and not 48 as previously believed. This enabled chromosome maps to be made, and by 1959 it was possible to see that 80% of those termed as Klinefelters had three sex chromosomes instead of two. The remaining 20% was made up of extra X and Y chromosomes in various abnormal combinations.

XXXY, XXXXY, XXYY, XX/XXY, XY/XXY, XY/XXXY, XXXY/XXXXY, XXXYY, XXY/XX, XXY/XYY, XXY/XXXY, XXX/XXXY etc.

Sex chromosomes with a slash, denote mosaics, which means the human (or animal) has a mix of two distinct cell types.

What causes Klinefelter syndrome?

Klinefelter syndrome is the result of a random nondisjunction error in cell division that happens during meiosis, the division of parent cells to produce gametes (sex cells) in the parent (male or female cat). The cells destined to be sperm or an egg undergo meiosis, in which the 38 chromosomes in the cell separate, and produce two new cells with 19 chromosomes each. Why 19 and not 38? Gametes only contain 19 chromosomes so that when during fertilisation, the two cells combine to make the correct 38 chromosomes.

Normally, the egg will receive one copy of the X chromosome and the sperm will receive one copy of the X or one copy of the Y chromosome. However, if nondisjunction occurs, the egg or sperm will receive an extra copy of the X chromosome. If the egg or sperm carrying the extra X chromosome results in fertilisation, the kitten will have Klinefelter syndrome.

Possible outcomes

How does Klinefelter syndrome affect cats?

Chromosomes carry genes, which are made up of DNA. The cat has two copies of each gene (one copy from each parent)  which contains instructions that determine the kitten’s features, such as fur colour and pattern, eye colour, height etc. The addition of the extra X chromosome means extra proteins that can affect the function of multiple systems within the kitten.

In the case of cats with Klinefelter syndrome, the extra X chromosome is commonly associated with a failure of the testes to function properly, which explains why male calicos and tortoiseshell cats are usually sterile. Examination of testicular tissue from one tortoiseshell cat found degeneration of the tubules, hyperplasia of the interstitial tissue, and complete loss of germ cells.

Humans with Klinefelter syndrome can have cognitive dysfunction, small testicles and penis, low sex drive, enlarged breast tissue, reduced muscle mass, decreased facial and body hair, increased belly fat and reduced bone mineral content. Unfortunately, there is scant data on the effects of Klinefelter syndrome in cats and most of the information available is from human studies.

How to diagnose Klinefelter syndrome in cats

Most veterinarians and pet owners won’t be aware a cat has Klinefelter syndrome. Signs a male has Klinefelter syndrome can include:

• Small testicles
• Calico or tortoiseshell coat pattern in a male cat
• Inability to sire a litter
• Cognitive defects
• Insulin resistance

Confirmation of Klinefelter syndrome in humans is made by chromosomal analysis (karyotyping). However, there is generally no reason to test for Klinefelter syndrome in male cats.

Frequently asked questions

How rare are calico and tortoiseshell cats?

The incidence of calico or tortoiseshell in male cats is said to be 1 – 3,000. However, I have been unable to find a viable source for where this statistic came from. On a personal note, I have met one male tortoiseshell cat at a  cat show, and came across a male calico named Toby whose owner had reported him missing. She was unaware he was unusual until a number of followers commented.

If cats with Klinefelter syndrome are sterile, why neuter them?

While cats with Klinefelter syndrome may be sterile, they are still at risk of testicular cancer.

Are male calico and tortoiseshell cats expensive?

Male calico and tortoiseshell cats generally cost the same as cats with other coat colours and patterns.

What is the karyotype of Klinefelter syndrome in cats?

The karyotype (size, shape and number of chromosomes) is 47, XXY.

Does Klinefelter syndrome affect other animals?

Not only does Klinefelter occur in humans and cats, but it also occurs in dogs, pigs, sheep, horses, goats, mice, and Chinese hamsters. [1]

How common is Klinefelter syndrome in people?

The incidence is reported to be between 1 in 500 to 1 in 1000 males.

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