What is Congenital Chimerism

A chimera is an organism containing genetically distinct cells that originated from different zygotes, (union of an egg cell and a sperm cell), during sexual reproduction. Congenital chimerism is inherited or acquired and occurs rarely in humans. In vitro fertilization (IVF) increases the chances of congenital chimerism. Generally the condition goes unnoticed, unless there are physical abnormalities, such as ambiguous genitalia or uneven skin pigmentation.

One form of congenital chimerisn is Mosaicism, possibly a mutation of a single zygote which produces cells with different chromosomal makeup in one individual. Mosaicism may cause certain diseases, such as Down Mosaic Syndrome. Down syndrome mosaicism is the most common chromosomal mosaicism. These patients have combinations of cells with the typical number of chromosomes (46) and some cells with an extra chromosome 21, for a total of 47 chromosomes.

Patients with a low percentage of abnormal cells may not realize they have the condition because they do not show signs of one of the mosaicism diseases. It may only be discovered when an individual gives birth to a child that has the disease. For individuals who develop symptoms of one of the diseases, the outlook will depend on how much the mosaicism has affected organs and tissues in the body.

A less common form or congenital chimerism is tetragametic chimerism which occurs when two separate eggs are fertilized by two sperm and produce two zygotes which fuse, forming two distinct cell lines in the individual. The fusion of the two zygotes is as if two fraternal twins merged at a very early phase of development. The tetragametic chimera may be male, female or hermaphroditic. This can occur with IVF because two or more embryos are placed in the uterus to assure better chances of pregnancy. Women who have IVF have more twin pregnancies than usual, increasing the chances of the fraternal twins fusing, creating chimeric fetuses. These individuals have groups of cells in their bodies whereby one set of DNA may appear in the liver and another set may appear in the lung. Even with different sets of DNA in human chimeras, physical abnormalities may not be apparent.

Two important legal cases of Karen Keegan and Linda Fairchild forced the system to grapple with chimerism as it relates to proving parenthood. These women’s DNA did not match their children. The cases proved that a complete reliance on DNA testing for maternity and paternity testing can be fallible.

One type of acquired chimerism is microchimerism, which occurs during pregnancy. The fetus and the mother are able to pass on undifferentiated stem cells to each other through the placenta. Only a small portion of the body has a distinct cell line from the rest of the body in microchimerism. Another type is congenital blood chimerism – non-identical twins who share a blood supply in the placenta can have blood stem cells pass from one twin and settle in the bone marrow of the other twin. Blood chimerism occurs in about 8 percent of non-identical twins.

There are similar cases for triplets. In one instance, a set of fraternal triplets (two boys, one girl) revealed chimerism of the red blood cells. There were Y chromosomes in 84% of the girls red blood cells and in 89/92% of the two boys’ cells, demonstrating there had been a reciprocal intra-uterine transfusion of blood stem cells.

Chimeras are of major interest to stem cell and organ transplant researchers. Chimeras can receive organ transplants from two sets of individuals that match either sets of their DNA, as opposed to most people who must find an identical match to their one set of DNA. Studying chimeras may assist the medical field in lowering the risk of organ transplant rejection and in better understanding immunological tolerance, since chimeras have to at two different cell lines in their bodies.