Gettysburg Medical News
The Clinical View
by P.E. Hoffsten, MD
2 August 2006

WHAT IS A CHIMERA?

            This week’s column is a change of pace from my usual preventive medicine urgings regarding high blood pressure, smoking, and diabetes.  Unlike those problems, there are certain medical situations that are thrust upon us over which we have no control.  Chimerism is one of those.

            A college student recently came to me requesting information about his brother who had been diagnosed with something called Klinefelter’s syndrome.  This is a condition that the person is born with.  It results from a genetic abnormality in which the person has two X chromosomes and one Y chromosome instead of the normal one X chromosome and one Y chromosome.  Normally, a male gets a Y chromosome from his father and an X chromosome from his mother.  Very rarely when a mother ovulates, she will release two eggs instead of one.  Even more rarely, the embryo that would result from the union of a sperm and an egg is then fused to an extra egg from the mother meaning that there is a population of cells in the embryo that has two X chromosomes and one Y chromosome.  These individuals are male but they are sterile.  They are usually very tall and do not develop the usual male secondary sexual characteristics such as hair around the armpits and around the pubic area.  They do not develop male muscular builds.  There maybe a slight speech impediment but intelligence is usually normal. Because of the lack of normal male secondary sexual characteristics and relative muscular under-development, these individuals are often the subject of derision and discrimination in high school when other young men are developing the usual male secondary sexual characteristics.  The brother of the individual with Klinefelter’s syndrome came to me saying that he had heard that Klinefelter’s syndrome was an example of chimerism.  He hadn’t been able to find good information about this and wanted to discuss what chimerism was and how his brother might be helped.

            From Greek mythology, a chimera was described as a creature with a lion’s head, a goat’s body, and a serpent’s tail.  It is said to have been a form of fire breathing dragon.  Unfortunately, somehow the name got applied to human beings who resulted from an accident of conception.

            I explained to him that chimerism was the name applied to an individual with an accident of conception.  The most illustrative example that I can think of is what happens with twins.  Identical twins result when the fertilized ovum called a zygote begins to divide.  On that first division when two cells are formed the two cells split apart making two human beings instead of one.  This will result in identical twins.  But much more common are what are called fraternal twins.  Fraternal twins result when a mother produces two eggs instead of one and both eggs are fertilized and implant in the uterus.  Both embryos can grow into babies that are twins but not identical.  They are two different individuals, not the same as identical twins.

            Chimerism results from an opposite event.  What would happen if two separate ova from the mother were fertilized by two separate sperm from the father?  If somehow those two zygotes were to meet together at one time and become one embryo instead of two, the result would be a chimera.  The chimera would be a single individual but with two different tissue types.  There might be no recognizable abnormality at all in the individual as the person grows up and reaches adulthood.  The only way such a person can be identified is with genetic testing.  Originally, such individuals were found accidently by recognizing that they had two different blood types.  Further studies demonstrated that sometimes a chimera will grow their liver from the cells of one of the contributing zygote while they may grow their kidney or their blood or their brain from the other fertilized egg (zygote) that is growing in the same body.  Everything works but they just have two different tissue types.

            Recently, this resulted in a legal case of disputed maternity in which a lady’s children were identified as having a tissue type that seemed different from her own.  As it turned out, she was a chimera and her ova had developed from one of her two zygotes while her blood had developed from the other zygote she was born from.  The result was that when they tested her blood, it was nothing close to that of her children and the courts were stating that she was not the mother of her own children.  Fortunately, additional tissue typing of her liver showed that indeed she was the mother of her children as she already knew (New England Journal of Medicine, 346, pages 1545-1552) and the case got settled.

            Cattle farmers are aware of something called a “freemartin”.   This is what occurs when cattle have twin calves.  Almost always, the calves are chimeras in which there is ambiguous sexual development.  Freemartins are not able to conceive and therefore don’t make breeding stock even though they might make tender beef.

            To return to the case of Klinefelter’s syndrome mentioned above, it is useful to make the diagnosis early.  In human’s, hormone shots can be administered to a person with Klinefelter’s syndrome and they can develop normal male secondary sexual characteristics and muscular strength.  This is a significant benefit to these individuals to avoid the derision and teasing that results in the locker room because of their perceived immaturity.  The person that came to me originally to ask the question about Klinefelter’s syndrome was advised that his brother could be benefitted by male hormone shots.

            When one thinks about all the possibilities that can occur at conception, I marvel that we ever come out normal.  Chimeras can come with an extra X chromosome to create Klinefelter’s syndrome (XXY) or Turner’s Syndrome (XXX).  Alternatively a chimera can have an extra Y chromosome (XYY) and be a “super male”. Fortunately, chimeras with sexual abnormalities are relatively rare accounting for less than 1% of the population.  But for the individual chimera with a problem, it is a 100% occurrence.