Tetrasomy 18p - What is it? [Continued]

How does this syndrome manifest itself? [Continued]

Was the preceeding clear? I know it's complicated but this was the simple stuff! Well, let me throw a bit of a curve ball at you. Because this stuff can get complicated pretty fast.

The first twist is mosaicism. Most genetic syndromes affect all the cells in the body. Which makes sense. But it is possible for a person to have a genetic syndrome that only impacts a percentage of their cells. This is called mosaicism, and it means that the syndrome impacts less than 100% of the body's cells. A genetics test can provide an estimate on the range of affected cells, and which cells are likely impacted.

Mosaicism is important because it means that the impacts of the syndrome are ammeliorated because it is not present in every cell. But it is currently impossible to tell just how impacted a child with tetrasomy 18p mosiac will be. And it means that it's probable that every child with mosaic tetrasomy 18p will unique. But it is also quite likely that the impacts will be less severe than a person who is not mosaic.

The other is the make up of that third chromosome (the isochromosome). I said on the other page that the isochromosome is made of of 2 copies of the p arm which become active. But just what is the make up of this extra chromosome? Are the 2 P arms that make this up identical? Are they both copies of the P arm from the same chromosome? Is the isochromosome made up of a copy of each of the p arms from the pair? Or, are each of the P arms of the isochromosome different, perhaps even from each other? For example, the "top" P arm may have microdeletions (pieces missing) that the "bottom" arm doesn't have. And the bottom "arm" could have microdeletions that the "top" arm doesn't have. It could get complicated, and it may be complicated but probably isn't.

Recent work by the Chromsome 18 Registry indicates that the usual makeup of the 4 P arms are that they are indeed 4 identical copies of each other, with no additional genetic material from the q arm being included. Meaning that at the molecular level the affected individual will usually have an extra set of the chromosomes found on the P arm of chromosome 18. Or put another way, they have 4 copies of the genes on the P arm instead of just the normal 2. And no one knows (yet) just what it means to have multiple copies of these genes. Look at the picture to the right; the science currently seems to say that P1 and P3 are identical and P2 and P4 are identical.

Based on the study, it's reasonable to lay out this likely scenario: Let's say that P arms 1 and 2 contain 50 genes each. So most people would go through life with 50 pairs of these 18p genes. If P arms 3 and 4 are exact copies of P arms 1 and 2, then the child, instead of having 50 pairs of 18p genes has 100 pairs of 18p genes, with each pair being doubled. They have twice the amount of 18 p genetic material that they should have.

This is just a hint of how complex it can get! Thinking about it gets so confusing. It is possible for there to be minor deletions in the P arm (maybe only 35 genes instead of 50) that gets duplicated across all 4 P arms or for material from other chromosomes (called a translocation) being present.

I hope that made some sense!

So what does this mean to the affected individual? Well, it's hard to get specific because until we know what the genes on the P arm do, it's impossible to predict what having twice as much means to the child's development and future. And the reason for going though all this explanations is that it is vital to understand that each child could have subtle but important distinctions about which genes are duplicated and that will govern the degree and kinds of impacts they may have. While the syndrome has a number of impacts, some appear only in 1 or 2 kids, while others appear more often. And some are mild and some are severe. And it is this genetic variation that probably explains why.

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