XXY or Klinefelter Syndrome?

This resource was originally compiled in 1999 by Vaughn Hambley (RIP) Carol Wilson and Ed Jensen, all three were at one-time board members of Klinefelter’s Support & Action (KS&A, aka AXYS). It was maintained by Vaughn as his personal website 47XXY.org, later known as 47XXY.ca and over the proceeding years underwent several revisions the last recorded was in 2016, from there on it was maintained in caretaker mode. Post-2016, there’s been a lot of advances in understanding 47XXY some good and some not so, the ‘not so’ is how the goalpost has shifted from a treatment model focused on genetic differences to one primarily centred on pathology namely Klinefelter’s Syndrome, described by Dr Harry Klinefelter as a rare disease of the testes.

Anyone who has ever been to a doctor will know their core business is in the treatment of diseases and because 47XXY is not a disease it then becomes easier to understand such a shift. This doesn’t necessarily mean you have to agree with what the doctor tells you, after all, they are just people like you and I, albeit people who could afford the tertiary education so they could tell you and me what to do. No, our advice is to read, absorb what you can and use the information herein to form your own opinions, maybe even educate doctors whose limited experience of Klinefelter’s Syndrome was learned from a paragraph in medical school.


47, XXY refers to the presence of an additional X chromosome in a person’s body cells. Some individuals who are 47, XXY do not appear any different from non-XXY individuals, and they may have mild symptoms or no apparent symptoms. During the first few years of life, most 47, XXY individuals do not show any obvious differences from typical infants. Children may have slightly weaker muscles, delayed development of motor skills, and learning and/or language problems. In later adolescence and adulthood, XXY individuals can develop features of Klinefelter syndrome, which can include primary hypogonadism (decreased testosterone production), small testes, enlarged breast tissue, tall stature, and/or other features. Although a large percentage of XXY individuals identify as males, some develop atypical gender identities. There have been reports of XXY individuals having a female physical appearance, but in most cases this was attributed to changes in specific genes related to sexual development. Most XXY’s are infertile, but some (mainly mosaic) produce sperm and may be able to conceive with assisted reproduction. Treatment varies among individuals and may include testosterone therapy for male identifying XXY’s or Estrogen for Female and those who identify as Non-Binary however, this therapy may not be appropriate for all individuals.

Under the Hood

There are 23 pairs of chromosomes found in each cell of the body, and each contain genes that determine our colouring, our features, and our sex. Women inherit two X chromosomes — one from each parent, written 46,XX.  Men inherit an X chromosome from their mothers and a Y chromosome from their fathers, written 46,XY.  Some individuals, however, have an additional X chromosome in their chromosomal arrangement, referred to as 47,XXY, or more commonly, just XXY.  The cause is unknown, yet XXY occurs in approximately 1 in every 650 live births, making it one of the most common chromosome variations. A small percentage of XXY’s are mosaic (47XXY/46 XY or 47XXY/46XX). XXY is identified in an individual in several ways, before birth via the process of Amniocentesis and thereafter either via Karyotype, Fluorescence In Situ Hybridisation (FISH) or Buccal Smear

How Did This Happen

XXY is caused by the presence of an extra copy of the X chromosome in the nucleus of every cell of the body resulting in 47XXY in place of 46XY. The extra chromosome is present in either the sperm or the egg that forms the individual (24 XY or XX instead of 23 X or Y. The presence of the extra chromosome is due to an error called nondisjunction

What Causes Non-disjunction

No one knows, its a natural occurring process present among all living things. It can occur in either the sperm or the egg in either the first or second meiotic division. For reasons that are not yet understood risk increases with advancing maternal age (greater than forty at time of conception) What they know is that non-disjunction is not caused by anything the parent does or doesn’t do either before or after conception occurs.

History

Your physician may have referred to this genetic variation as either XXY or Klinefelter syndrome.  Though these terms are often used interchangeably, they actually refer to two quite different, though related, things.  In 1942, Dr. Harry Klinefelter while working at the Massachusetts General Hospital in Boston published with fellow researchers a report about nine individuals who had similar features:

By the late 1950’s researchers discovered individuals with these features, had an extra X sex chromosome, and were XXY instead of a typical XY male arrangement. Subsequent research studies expanded and revised the original features to include the following as possible associated conditions

Some researchers list all of these as being Klinefelter syndrome.  However, there is a trend among modern practitioners to distinguish chromosomal variations from any possible resulting syndromes, diseases, and conditions.  It is important to remember that not all XXYs will develop any or all of these conditions.  Since your extra X is just one out of 47, you have a lot of other genetic material that affects you in a variety of ways, and the extra X can differ in genetic coding from individual to individual.

Further, “Klinefelter syndrome defines characteristics that are only unusual if found in a male. Common symptoms, such as low testosterone and breast development, are not unexpected features (or symptoms) if identified in a female. Therefore, for an individual with an XXY karyotype who does not identify as male, Klinefleter syndrome may not be a suitable diagnosis. In essence the only consistent commonality shared by all XXY’s is the diagnosis.

Medical issues not associated with XXY or Klinefelter Syndrome

  • Genito-Urinary Tract Issues: 
    Kidney Stones, Bladder Infections, Erectile Dysfunction, Premature Ejaculation
  • Ear, Eyes, Nose and Throat Issues: 
    Tinnitus (ringing of the ears) Hearing Loss, Wax Build Up, Balance Problems, Vision Problems
  • Endocrinology: 
    Hypothyroidism
  • Neurological:
    Dizziness, Memory Loss
  • Kallmann Syndrome
  • Chimerism 46,XX/46,XY
  • 48,XXYY syndrome
  • 47,XYY

Treatment

Due in part to the lack of research and in part to the large variability of symptoms and characteristics, there is no single formula or treatment regime that is correct for every XXY.  As a consequence, each individual must assume responsibility for their own health care and advocate to be treated as an individual until the appropriate formula and treatment regime is ascertained. Finding that proper care begins with identifying the health care professionals who will work with you toward that goal.  XXY’s will most likely be treated by an endocrinologist, a medical specialist who treats the endocrine (hormone producing) glands.

Conclusion

If you, or a member of your family, have been recently diagnosed it is important to remember that while there may be challenges, the situation is far from being hopeless.  With good information, support, and a knowledgeable medical provider who is willing to work with you or your child, any medical issue that may be associated with the presence of an additional X chromosome can be addressed.  Accordingly, take responsibility for your own healthcare and learn all you can about how being an XXY might affect you or your child.  Begin now to seek out the medical and psychological treatment and support network that may be needed.


Original compilation by Vaughn Hambley (RIP) Carol Wilson and Ed Jensen. Updated April 2020 by Candice Cody, Administrator @The XXY Project