College of American Pathologists
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Understanding the disorder and the markers

December 2001
Anne Paxton

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Of all the chromosome disorders, Down syndrome is the least likely to be fatal to the fetus. "All chromosomes have the potential to have an extra copy in the embryo through non-disjunction, which is the failure of a chromosome pair to separate during meiosis," explains Dr. Jacob Canick, director of prenatal and special testing for Women and Infants Hospital of Rhode Island and professor in the Department of Pathology and Laboratory Medicine at Brown University.

Dr. Canick notes that trisomy for almost every chromosome is lethal in embryonic development. The reason fetuses with trisomy 21 tend to live is because that chromosome, compared with the others, provides the smallest amount of genetic information. (The 22 autosomal [or non-sex] chromosomes are numbered in decreasing order by size, except that 21 and not 22 is the smallest.)

Trisomy 21 is the most common chromosomal abnormality with which the fetus can survive until birth; with trisomy 18 and 13, for unknown reasons, the fetus often lives to birth but not too much longer. All the other trisomies are not compatible with embryonic development and result in early spontaneous abortions, usually not even a proper implantation.

Although it is the most common genetic cause of moderate mental retardation, Down syndrome, caused by an error in cell division, is for the most part not inherited. A patient’s family history usually has no bearing on her risk of having a Down pregnancy. Maternal age, however, does have a bearing.

The cause of the association between the screening markers and Down syndrome is relatively unknown compared with our knowledge of how to use the markers in screening, says Dr. Andrew MacRae, director and CEO of The Research Institute at Lakeridge Health, Oshawa, Ontario, Canada. "Generally, in Down syndrome, substances produced by the placenta tend to be higher in maternal circulation, possibly to support a poorly functioning fetus, whereas substances produced by the fetus tend to be lower. So estriol is lower and AFP is lower, as both are produced primarily by the fetus. In the case of estriol, it’s the fetus and mother combined."