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 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 that shift in focus. It 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 a medical textbook.
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 non–disjunction
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.
In 1942, a young doctor by the name of Harry Klinefelter was assigned to work with Dr. Fuller Albright who was commonly considered to be the father of Endocrinology at Massachusetts General Hospital in Boston. During his fellowship, Dr. Klinefelter examined and subsequently prepared a case study concerning nine adult men with a common set of symptoms. Dr. Albright encouraged his young associate to be the lead author on the study, which was published in the November 1942 issue of The Journal of Clinical Endocrinology, and the combination of symptoms that Dr. Klinefelter described therein has since been referred to as “Klinefelter Syndrome”.
- Tall (around 180cm)
- Small testes or Hypogonadism
- Inability to produce sperm
- Failure to Virilise
In 1956, some fourteen years after Dr. Klinefelter published his case study, Drs. Joe Hin Tjio and Albert Lavan confirmed there were twenty-three pairs of chromosomes in humans. Up until that time, it had been thought there was twenty-four, but using a more advanced experimental methodology, Tjio and Lavan were able to confirm that there were, in fact, only twenty-three pairs. This discovery marked the beginning of modern Cytogenetics the study of chromosomes and the variations caused by either numerical and/or structural differences in them.
Three years later, in 1959, a young English researcher named Patricia Jacobs and her associate published a study correlating forty-seven chromosomes – that is one more than commonly found in humans – with Klinefelter Syndrome. Because the extra chromosome Dr. Jabobs discovered was an extra X, the Karyotype for this individual became known as 47XXY. Subsequent research expanded and revised the original features to include the following as possible associated conditions
- Autoimmune Diseases
- Brain Differences
- Metabolic Syndrome
- Cognitive Differences
- Developmental Concerns
- Risk of Pulmonary Embolism
- Essential Tremor (20 – 50%)
- Gender Dysphoria
- Motor Skills and Adaptive Functioning
- Emotional and Mental Health
- Venous Disease
Some researchers list all 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.
Are 47,XXY and Klinefelter Syndrome the same thing?
If all persons with the set of symptoms described by Dr. Klinefelter had an extra X chromosome, or if all persons born 47,XXY had the symptoms described by Dr. Klinefelter, then the two terms would be interchangeable. However, this is not the case. Consider the following two questions –
Does everyone with Klinefelter’s Syndrome have an extra X chromosome? The answer is no. In 1985, Dr. Klinefelter published an article in which he summarised what had been learned about the Klinefelter’s during the more than 40 years since his having first identified it. He wrote: “the Syndrome has been found to be a chromosomal variation, in which there is an extra X chromosome in 80% of patients.
Does everyone born with an extra X chromosome have Klinefelter syndrome? This answer is “No.” Females born with an extra X are Trisomy X; and while all males who are born with an extra X chromosome are at risk of developing Klinefelter Syndrome, for currently unexplained reasons, there is broad phenotypic variability and many of these 47,XXY individuals may not develop one or more of the distinguishing signs and symptoms.
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 females. Therefore, for an individual with an XXY karyotype who does not identify as male, Klinefelter Syndrome may not be a suitable diagnosis. 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
Dizziness, Memory Loss
- Kallmann Syndrome
- Chimerism 46,XX/46,XY
- 48,XXYY syndrome
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. Therefore, everyone 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 be treated by an Endocrinologist, a medical specialist who treats the endocrine (hormone producing) glands.
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: Vaughn Hambley (RIP) Carol Wilson and Ed Jensen. Updated April 2020 by Candice Cody, Administrator
@The XXY Project