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Down Syndrome Abstract
of the Month: July 2003

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Down syndrome: a study of chromosomal mosaicism.

Modi D, Berde P, Bhartiya D.
Reprod Biomed Online. 2003 Jun;6(4):499-503.

Cell Biology Department, Research Society, Bai Jerba Wadia Hospital for Children, Acharya Donde Marg, Parel, Mumbai, India.

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Recent data suggest that chromosome mosaicism is a possible mechanism for intrauterine and postnatal survival in cases of trisomy 18 and Turner syndrome (45X). The aim of this study was to evaluate if chromosomal mosaicism is a possible mechanism of survival in Down syndrome (DS) (trisomy 21) individuals. Mosaicism was studied by interphase fluorescence in-situ hybridization (FISH), using a specific probe for chromosome 21 (21q22.13-21q22.2) in 78 cases suspected of DS. To rule out tissue specific mosaicism, buccal cells or amniocytes were analysed in addition to blood in 20 DS cases. Thirty-three per cent of the cases studied by FISH in only peripheral blood were mosaics. In 20 cases of trisomy 21, two tissues were studied and mosaicism was not detected in either of the two tissues in 15 cases. The remaining five cases were mosaics in both the tissues analysed. Clinical comparisons in 17 DS mosaics showed a direct relationship between the percentage of trisomic cells and the degree of phenotypic manifestations. These results suggest that mechanism(s) other than mosaicism may exist for the intrauterine and postnatal survival of DS cases.

My comments:

First, some background.

At least 25% of conceptions are lost before the fertilized egg implants in the uterine lining, and approximately 15% of recognized pregnancies miscarry. The presence of an extra chromosome is responsible for more than half of these losses. An extra chromosome (trisomy) has been documented as possibly occurring with every chromosome, and is usually considered lethal to the embryo. Notable exceptions include trisomy 21, in which 20 to 25% of conceptions make it to birth, and trisomies 13 and 18, in which 5% make it to birth.

Researchers have been curious as to why these trisomies have a higher survival rate than trisomies of the rest of the chromosomes. In the last three years, it has been shown that all live babies with trisomy 18 are mosaic; that is, some cell lines are normal and other cell lines have an extra 18th chromosome. The current thinking is that embryos with mosaic trisomy 18 are better equipped to survive than babies with full trisomy 18. Similarly, a study of patients with Turner syndrome (loss of one sex chromosome) showed a rate of 75% mosaicism. So, do we see the same thing with trisomy 21?

While previous studies have shown less than 5% of people with trisomy 21 have a form of mosaicism, most of these studies have only looked at simple blood tests of chromosomes. In this study, the researchers decided to try to get a better idea of how many people with Down syndrome might have mosaicism by using a more detailed test of blood cells and also looking at other body tissues.

The researchers took 78 children with known or suspected DS, ages 2 days to 6 years. 70 of the 78 children had trisomy 21 blood cells. 23 of these 70 children showed mosaicism in the blood cells when examined by a special test called a FISH probe (more detailed than the typical chromsome examination). This works out to 33% mosaicism rate, which while higher than previously thought, is nowhere near the high numbers seen in trisomy 18 and Turner syndrome. Incidentally, the researchers also looked at physical features and could find no feature or combination of features (or lack thereof) that were more likely seen with mosaicism.

Is it possible that in the children with non-mosaic DS there could be other tissues beside blood that showed mosiacism? 20 children were chosen randomly to test both blood and a scraping from the inside of the mouth or blood and amniocytic fluid cells. Of these 20, 5 were mosaic in both cell lines; the other 15 had no mosaicism in either cell line.

The conclusion here is that while mosaicism is more common in people with Down syndrome than previously thought, it is not common enough to be the reason for survival of a large percentage of fetuses with Down syndrome.

I know that a lot of parents reading this will now wonder if they need to have their child tested for mosaicism. The answer is no, since the diagnosis of mosaicism doesn't change anything. While the popular conception of mosaic Down syndrome is that these children are less affected physically or mentally, there is no proof that this is the case.

For more information on Mosaic DS, see this page on my website.

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