Mosaic comes from the Greek word mouseios which means of the muses, artistic.

With mosaicism there is a chromosomal anomaly, but not in every cell. Some cells have the "normal" complement and arrangement of chromosomes and some cells have the chromosomal anomaly.

So for example in the case of Trisomy 18 there are three complete 18^th chromosomes. With Trisomy 18 mosaic some cells have the three complete 18th chromosomes, but some cells have the normal complement of two complete 18th chromosomes.

Mosaicism can happen with any chromosomal anomaly, not just "full" trisomy. For example, with Trisomy 18q all the cells have the additional q arm of the 18th chromosome. With Trisomy 18q mosaic, some cells have the additional q arm, and some have the "normal" complement of two complete 18 chromosomes.

Children with a mosaic diagnosis have just as much risk of early death as those with a "full" diagnosis. It is not the chromosomal anomaly itself which causes the early death of our children but how the changes in the genetic material effects the developing baby. Children with a mosaic diagnosis are just as likely to have life threatening cardiac problems, apneas, feeding problems and other potentially life threatening or life shortening congenital problems.

In some ways a mosaic diagnosis is very unpredictable and challenging for both the parents and the effected person.

Unfortunately the true effect of mosaicism depends not only on how many cells are effected (percentage), but where those cells are (distribution).

When doctors test for chromosomal anomalies, they generally take a sample of cells using a minimally invasive method. Most often, after birth this is via blood, or more correctly they look at "peripheral lymphocytes". While blood is a good sample to test it does not reveal what is happening in other body systems, eg skin, brain, heart, kidneys etc. Depending on when during embryonic development the mosaicism occurred, different body systems may have vastly different percentages of the chromosomal anomaly. Some may not have any evidence of cells with the chromosomal anomaly at all.

To test every organ and body system would be unethical and very invasive. However no-one can tell, without doing biopsies of every organ system, just what an individuals distribution of cells with a chromosomal anomaly is. As a result it is almost impossible to predict how an individual will be effected.

So if "more effected" means cognitive ability, then someone who has 85% of their peripheral lymphocyte cells with the chromosomal anomaly may actually be "less" effected than someone who has 10% if the effected cells do not happen to lie within the brain.

As a result the "numbers" are not there for studies to be done and reports in the medical literature tend to be skewed towards the more "unusual" cases of mosaicism. For example in Trisomy 18 mosaic the cases reported in the medical literature tend to be single case studies of individuals with high percentages of trisomic cells but with high cognitive functioning and few physical anomalies.

How does mosaicism occur?

The distribution of the cells with the chromosomal anomaly depends on when exactly the original error occurred. If it occurred before the second week after conception, which is approximately when the fertilised egg begins to differentiate into body systems then the distribution is likely to be more "even" across the all the body systems. If it occurs after this then the distribution is more likely to be "uneven" with some body systems having a higher percentage of cells with the chromosomal anomaly than others. In fact some body systems may have no sign of the chromosomal anomaly.

Again distribution of the effected cells is variable, depending on when and where the correction happened.

Testing for Mosaicism.

To confirm the laboratory may repeat the study and or look at more cells than they would have with routine testing. The percentage is then calculated based on the number of cells with a chromosomal anomaly and those without.

How many cells?

I have mentioned previously that some doctors believe all surviving children with a trisomy are in fact mosaic. Many ask how they can say that when there are no "normal" cells seen in the chromosome analysis?

When a chromosome analysis is done anywhere between 5 and 100 cells are usually looked at. This is only a small number of the many billions of cells in our body, and the cells examined are simply a random sample of cells that happened to be there at that particular time. Obviously the more cells that are looked at, the greater the level of accuracy. And similarly the more body systems looked at the greater the chances of detecting any mosaicism that may be present.

So for example if 5 cells are examined and one cell shows the chromosome anomaly then the percentage would be 20%. It would then be expected that if 100 cells were looked at that there would be 20 cells showing the chromosomal anomaly. However if 100 cells were looked at only 2 cells showed the anomaly the percentage would be 2% and it is very possible that if a smaller number of cells were looked at that it would not have been seen.

Most often routine karyotyping is the test initially performed. This is costly and labour intensive. It involves culturing the cells until they reach a certain stage of cell division, they are then stained and looked at manually to determine the arrangement. This takes time and the results of this type of chromosomal analysis may take up to 2 weeks, sometimes more if the test needs to be repeated or checked at any stage. Depending on the laboratory protocol anywhere between 5 and 100 cells are looked at, but most often it is a smaller number around 20 unless mosaicism is suspected because it is more cost effective.

Recently a newer type of chromosomal testing has become more widely used, especially in the determination of mosaicism. It is called a FISH test (Fluorescence In Situ Hybridisation). The benefits of a FISH test are that it is possible to look at much larger numbers of cells at one time, for example 500 cells as opposed to 20 and the results are available very quickly as culturing is not necessary.

Similarly a FISH test may show three signals for the 18th chromosome but it does not tell the technician if that signal comes from a whole extra chromosome or part of an extra chromosome. For this reason all results from a FISH test are considered preliminary until a cultured karyotype is performed to confirm the results.

As FISH testing becomes more widely used and laboratories develop better probes the more accurate the results will be. For example a single FISH test has been developed for the rapid detection of the most common trisomies, trisomy 13, trisomy 18, trisomy 21 and triple X syndrome. While its is less specific than a test for trisomy 18 alone it will still not detect a trisomy of other chromosomes eg trisomy 9. This can only be done at this stage using a probe specific for trisomy 9 or by a cultured karyotype.

Margins of Error

There is no way that I can possibly cover all the possible sources of error here, and the incidence is really quite small. The most common question that I am asked is if a mistake was made when percentages of effected cells changes over time. In general the answer to this is no, it is simply an artifact of the random nature of the cells taken for chromosome analysis. It is possible that as a person grows "cell rescue" may occur (see above for the theory of cell rescue) but there is no strong evidence that this is in fact the case.

If you have any concerns about the reliability of the chromosome testing done, please discuss these with your geneticist or genetic counsellor. This information is simply provided as a guide.

Not enough cells looked at to determine a low level of mosaicism, that is a small number of "normal" cells or a small number of cells that have a chromosome anomaly.

In a cultured karyotype it is possible that only the normal cells "grow" or vice versa.

The level of skill of the person or laboratory in doing and examining a cultured karyotype, though in general cultured karyotypes are normally checked by more than one person.

Simply by the laws of averages every person alive probably has some random trisomy cells but that they do not indicate a trisomy disorder. It may just be "luck" that this cell turns up in the actual test, hence low levels of "abnormal" cells should be viewed cautiously.

Placental mosaicism. Sometimes only the placenta has some cells with an abnormal chromosome arrangement. This does not mean that the baby has a trisomy disorder or that the baby will be effected by the arrangement. Placental mosaicism is most commonly seen in CVS testing and generally an amniocentesis will confirm whether this si the case.

Even though FISH testing is considered "more" accurate errors may still occur. For example signals from a FISH test may fade before they are seen and counted.

Finally, chromosome testing is becoming more accurate. Consequently results that were obtained 20 years ago may differ to results obtained today. This is not because anything has changed necessarily, in fact that is highly unlikely. However tests have become refined and knowledge more advanced. As a result your geneticist may suggest further testing.

A final personal comment. No matter what the test results reveal about chromosomal arrangements in an individual these results will not change anything about them. They will always be the same unique individual that we love. It is very easy to become lost in the scientific explanations and forget to see the person behind the test results.

What is a translocation?

What is a karyotype?

 What is a chromosome?

 The human egg & sperm cell

 How does a trisomy happen?

 What is "full" trisomy?

 What is a partial trisomy?

 What is a translocation?

  What is mosaicism?

 What is a karyotype?

 What is a Phenotype?

 What is prenatal testing?

 How is a diagnosis made?

 Will my baby die?

 Why did this happen to me?

 What are the risks of it happening again?

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