47, XXY

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 noticeable differences from typical infants. Children may have slightly weaker muscles, delayed development of motor skills, learning and language problems. In later adolescence and adulthood, XXY individuals can develop Klinefelter syndrome features, including primary hypogonadism (decreased testosterone production), small testes, enlarged breast tissue, tall stature, or other features. Although a large percentage of XXY individuals identify as male, some develop atypical gender identities. There have been reports of XXY individuals having a female physical appearance, but in most cases, this is related to changes in specific genes around sexual development. Most XXY’s are infertile, but some (mainly mosaic) produce sperm and may conceive with assisted reproduction. Treatment varies among individuals and may include testosterone for those who identify as male, Estrogen for females and those who identify as Non-Binary; however, hormonal interventions may not be appropriate for everyone.

Under the Hood

There are 23 pairs of chromosomes found in each cell of the body, and each contains 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 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 after that either via Karyotype, Fluorescence In Situ Hybridisation (FISH) or Buccal Smear

How Did This Happen

XXY relates to an extra copy of the X chromosome in the nucleus of every body cell, indicating 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. It is a naturally 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 unknown, risk increases with advancing maternal age (greater than forty at time of conception). Non-disjunction is not the result of anything the parent does or doesn’t do either before or after conception occurs.

History

In 1942, a young doctor named Harry Klinefelter was assigned to work with Dr Fuller Albright, commonly considered 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 become the lead author of the study, published in the November 1942 issue of The Journal of Clinical Endocrinology. The combination of symptoms Dr Klinefelter described has since become known as “Klinefelter Syndrome”.

In 1956, some fourteen years after the publication of the case study, Drs. Joe Hin Tjio and Albert Lavan confirmed there were twenty-three pairs of chromosomes in humans. Up until then, researchers believed there was twenty-four. By using a more advanced experimental methodology, Tjio and Lavan confirmed 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 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 (one more than commonly found in humans) with Klinefelter Syndrome. Because the extra chromosome Dr Jacobs 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 associations.

Some researchers associate all with 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 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 various 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 Klinefelter’s during more than 40 years since he 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. While all males born with an extra X chromosome are at risk of developing Klinefelter Syndrome, there is broad phenotypic variability for currently unexplained reasons. 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 an appropriate diagnosis. The only consistent commonality shared by all XXY’s is the diagnosis.

Medical issues not directly related to XXY or Klinefelter Syndrome

  • Genito-Urinary Tract Issues: 
    Kidney Stones, Bladder Infections, Erectile Dysfunction, Premature Ejaculation
  • Ear, Nose and Throat Issues: 
    Tinnitus (ringing of the ears) Hearing Loss, Wax Build Up, Balance Problems
  • Neurological:
    Dizziness, Memory Loss

Treatment

Due partly to the lack of research and 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 health care and advocate to be treated as an individual until the appropriate formula and treatment regime is forthcoming. Finding that care begins with identifying the health care professionals who will work with you toward this goal. An Endocrinologist undertakes treatment for XXY’s, 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 essential to remember that while there may be challenges, the situation is far from 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 healthcare and learn all you can about how being an XXY might affect you or your child. Begin now to seek out the appropriate medical or psychological services that are right for you.


Related: Comprehensive Study of KS/47XXY

Original compilation: Carol Wilson, Ed Jensen & Vaughn Hambley (RIP)
Updated by Candice Cody, Administrator
@The XXY Project