Extra or Missing Chromosomes

How do you calculate the risks of having a child with Trisomy 21 if the mother is 44 years old, the father is 46 years old and there has already been one miscarriage due to Trisomy 21?

-A curious adult from the U.S.

June 4, 2014

Two of the three factors you’ve mentioned are important for figuring out the risk for having a child with Trisomy 21 or Down syndrome.  The one that doesn’t play a big role is the age of the dad. 

Of the other two, the one that usually matters most is mom’s age.  As you can see in the chart below, a mom’s chance of having a child with Down syndrome gets higher as she gets older.

So, in most cases, a 44-year-old woman would have around a 3% chance of having a child with Down syndrome.  The flip side of that means she has a 97% chance of not having a child with Down syndrome. 

The final risk factor is one that depends on why a couple had a child with Down syndrome in the first place.  Most cases of Down syndrome are the result of a mistake that happens when an egg or sperm gets made.  This just happens by random chance, so having one child with Down syndrome for this reason usually doesn’t really increase your chance for having a second.

There are a few cases though where Down syndrome is more common in a family for genetic reasons.  One of these is something called a translocation. 

If mom has a translocation, then the chance to have a child with Down syndrome can go up to around 10-12%. If dad has the balanced translocation, then the chance is about 3%. A family can tell if this is the issue with a blood test on mom and dad that looks at their chromosomes.

So that is how to calculate the risks in this case.  Assuming there isn’t a balanced translocation, then the only big factor is mom’s age.  At 44, there is about a 3% chance for her child to have Down syndrome.

Now I want to talk a little bit about why as a woman gets older her chances for a child with Down syndrome increase. Then we will talk about the type of Down syndrome that can “run in a family.”

The Problem with Older Eggs

We can’t talk about Down syndrome without talking about chromosomes. You might remember that chromosomes are the packages of instructions that are in every cell of our body.  They tell our bodies what to look like, how tall to grow, and how to function.

Humans usually have 23 pairs of chromosomes.  We get one of each pair passed down from mom and one of each pair from dad. 

Sometimes, there is a random mistake when the sperm or egg is being made. This causes there to be extra or missing chromosomes passed down from that parent. If this happens with an extra copy of chromosome 21, it causes Down syndrome.

This happens by random chance, but this chance goes up as a woman gets older. This is because women are born with all of the eggs they are ever going to have and as a woman gets older, her eggs get older too.

So the older the egg is when it is getting ready to package only half of the chromosomes to pass down (one of each pair), the higher chance that a chromosome pair will get stuck together. This is what happens with Down syndrome, the chromosome 21 pair gets stuck together.

There is also a higher chance as women get older of the other chromosome pairs getting stuck together when they are getting packaged into an egg, but Down syndrome we see in pregnancies and babies that are born.

A mistake in packaging of chromosomes can happen with dad too, but the chances really don’t get higher as dad gets older. That is because men are constantly producing new sperm every couple of weeks, so there isn’t a higher chance that the chromosomes will get stuck together. But as you can see here, children of older dads are at a higher risk for a different set of conditions.

So if a couple has had a previous pregnancy with Down syndrome for this reason, then the chance of having a child with Down syndrome is usually low, about 1 in 100 or if she is 40 or above, whatever her chance is due to her age.

Balanced Translocations

Now that we talked about Down syndrome that just happens by random chance, let’s talk about Down syndrome that can “run in families.” This happens if Down syndrome is caused by a translocation. What that means is that one chromosome gets stuck to another chromosome.

About 4% of cases of Down syndrome are caused by something called a Robertsonian translocation, also known as Translocation Down syndrome. This can be random or inherited from a parent. This happens when the extra copy of chromosome 21 becomes attached to another chromosome. To learn more about how this happens, click here

You can see an example where the extra copy of chromosome 21 is attached to the top of chromosome 14 in the image below:

Even though it is arranged differently, there are still three copies of chromosome 21 and this still causes Down syndrome. 

To see if it was inherited, you have to see if one of the parents has a translocation as well. This can be done by a blood test on each parent.

If Down syndrome was inherited, one parent would have chromosomes that looked something like the picture below:

Here one copy of chromosome 21 is attached to chromosome 14, but there is only one other copy of chromosome 21. This is called a balanced translocation. The parent has the typical number of chromosomes just arranged in a different way so the translocation usually does not cause any health problems for the person.

The reason it can be helpful to know if Down syndrome was caused by a translocation is because it will change your risk. If a parent has a balanced translocation, the chance of passing down an extra chromosome to a child depends of which parent has the translocation. There is about a 3% chance for Down syndrome to happen again if dad has the translocation and about a 10-12% chance if mom has the translocation. To find out more about these numbers, click here.  

So the most likely scenario is that Down syndrome in your previous pregnancy was random and not the type that is inherited. If this is true, the chance of having a child with Down syndrome would be around 3%, and a 97% chance of not having a child with Down syndrome.

By Katie Kobara, Stanford University

Mom's age is usually the biggest risk factor for having a child with Down syndrome.

The chromosomes are arranged in pairs and this is what they look like under a microscope. A has the usual 46 chromosomes while B has an extra chromosome 21 as indicated by the red circle. 

The most common way for someone to end up with Down syndrome is if mom's egg has an etra chromosome 21.