Klinefelter's Syndrome

Klinefelter's syndrome only occurs in males and results from a congenital abnormality of the sex chromosomes, X and Y. Normally a male has only one X and one Y chromosome and a female has two of the X-chromosomes. In Klinefelter's syndrome, two or more X-chromosomes are present in addition to one Y chromosome. The X-chromosomes contain a large amount of genetic material that has many effects beyond those that determine sex. Klinefelter's syndrome usually is not present in other family members, but occurs as a new mutation.

Manifestations of this genetic disorder are highly variable depending on the number of extra X-chromosomes. Infertility is exceedingly common if not universal, so the diagnosis often is made in the course of investigation for this problem in adult life. Many men with Klinefelter's are unusually tall due to abnormally long limbs. The testicles may be small and the breast tissue enlarged (gynecomastia).

At present, there is no treatment available that can correct the genetic abnormality. Testosterone therapy may benefit decreased libido, if that is a problem, and also may improve secondary sexual characteristics such as beard growth. According to the NIH (www.NIH.org), the XXY chromosome arrangement appears to be one of the most common genetic abnormalities known, occurring as frequently as 1 in 500 to 1 in 1,000 male births. Although the syndrome's cause, an extra sex chromosome, is widespread, the syndrome itself-the set of symptoms and characteristics that may result from having the extra chromosome-is uncommon. Many men live out their lives without ever even suspecting that they have an additional chromosome.

Recently, the term "Klinefelter syndrome" has fallen out of favor with medical researchers. Most prefer to describe men and boys having the extra chromosome as "XXY males." In addition to occasional breast enlargement, lack of facial and body hair, and a rounded body type, XXY males are more likely than other males to be overweight, and tend to be taller than their fathers and brothers.

For the most part, these symptoms are treatable. Surgery, when necessary, can reduce breast size. Regular injections of the male hormone testosterone, beginning at puberty, can promote strength and facial hair growth-as well as bring about a more muscular body type.

A far more serious symptom, however, is one that is not always readily apparent. Although they are not mentally retarded, most XXY males have some degree of language impairment. As children, they often learn to speak much later than do other children and may have difficulty learning to read and write. And while they eventually do learn to speak and converse normally, the majority tend to have some degree of difficulty with language throughout their lives. Ideally, XXY males should begin testosterone treatment as they enter puberty. XXY males diagnosed in adulthood are also likely to benefit from the hormone. A regular schedule of testosterone injections will increase strength and muscle size, and promote the growth of facial and body hair.

The vast majority of XXY males do not produce enough sperm to allow them to become fathers without medical assistance. If these men and their wives wish to become parents, they should seek counseling from a Reproductive Endocrinologist regarding their options.

However, no XXY male should automatically assume he is infertile without further testing. In a small number of cases, XXY males have been able to father children without medical assistance. Along with having cells with the XXY chromosome count, these males may also have cells with the normal XY chromosome count. If the number of XY cells in the testes is great enough, the individual should be able to father children.

Although the missing testosterone due to disfunction in the testes can be artificially supplied, the changes in the testes that lead to infertility are not preventable. However, new studies have shown that in some cases, Klinefelter males can indeed become fathers. The first question that had to be answered before further research could be done was whether or not infertile Klinefelter men produce any functional sperm at all. This question was answered in a study done by Cozzi et. al. in which cells to form spermatozoa was confirmed. With the knowledge that viable spermatozoa may exist in these men, the next step was to try to access it.

In a study conducted by Tournaye et. al., the possibility of recovering testicular spermatozoa from XXY patients for use in intracytoplasmic sperm injection (ICSI) was investigated. If spermatozoa can be recovered from Klinefelter's males, ICSI allows their partners' eggs to be impregnated and placed in the uterus for normal development. Therefore, the Klinefelter man's sexual incapacity is overcome. This is a common infertility treatment for couples. The feat in making it work in an XXY male is the actual recovery of sperm.

In four out of nine patients, spermatozoa were recovered from testicular tissue. Although the results proved this to be a fairly successful infertility treatment, the authors consider the procedure experimental with concerns for the chromosomal normality in the embryos generated by ICSI. This complex treatment involves multiple testicular biopsies and preimplantation diagnosis of embryos, making it much more complicated than it sounds.

This is an enormous step in refining infertility treatment of Klinefelter males. Although it is still experimental, it has been proven to work and exists as an option for couples capable of enduring the emotional, physical, and financial hardships of the procedure.

Resources for further information:

K' S. and Associated
P.O. Box 119
Roseville, CA 95678
Support group for XXY males as well as males with other sex chromo-some disorders. Operated by "Melissa," mother of a 12-year-old XXY boy Provides literature on XXY males and other chromosome disorders, periodic newsletter.

Works Cited

1. Cozzi J., Chevret E., Rousseaux S., Pelletier R., Benitz V., Jalbert H., Sele B. 1994. Achievement of meiosis in XXY germ cells: study of 543 sperm karyotypes from an XY/XXY mosaic patient. Human Genetics. 93: 32-4.
2. Staessen C., Coonen E., Van Assche E., Tournaye H., Joris H., Devroey P., Van Steirteghem A., Liebaers I. 1996. Preimplantation diagnosis for X and Y normality in embryos from three Klinefelter patients. Human Reproduction. 11: 1650-53.
3. Tournaye H., Staessen C., Liebars I., Van Assche E., Devroey P., Bonduelle M., Van Steirteghem A. 1996. Testicular sperm recovery in nine 47, XXY Klinefelter patients. Human Reproduction. 11: 1644-49.