What Causes Down Syndrome?

One of the foremost questions in my mind when I first found out my baby’s diagnosis was, “How did this happen? Was it something I did?"

I know my boyfriend was thinking similar thoughts, and blaming himself since he has a cousin with Down syndrome. In fact, when the doctor was initially telling us about all the screening tests offered, I wasn’t quite sure I wanted any performed. My boyfriend insisted, however, since my insurance covered the tests and he didn’t have much faith in his genetic line. This concern was despite the doctor’s opinion that his cousin was a distant enough relation that it was highly unlikely the Down syndrome would be inherited.

 

Three Types of Down Syndrome 

 

What I didn’t know at the time, and what wasn’t explained until after I learned the diagnosis, was that there are actually three types of Down syndrome, or Trisomy 21: Nondisjunction, which accounts for approximately 95% of all cases; Mosaicism, which accounts for 2-3% of cases; and Translocation, which accounts for the remaining cases and is the only inheritable type. My little girl, like the majority of those with Down syndrome, has Nondisjunction Trisomy 21. The genetic counselor briefly explained to me that this is due to the failure of chromosome 21 to separate which results in 3 copies in the affected individual.

 

It wasn’t until I got back home and fired up Google (or maybe it was Bing), that I started to truly understand how this occurred. I needed to have answers, because I couldn’t help but blame myself for causing my daughter’s Down syndrome. After all, I had done quite a bit of drinking between my sister’s bachelorette party and wedding before I realized I was pregnant. I had convinced myself that this is what caused my baby girl’s extra 21st chromosome. It may sound strange, but somehow it was easier to take the blame instead of just admitting that things beyond my control will just happen. What I learned made me realize that nothing I did caused the Down syndrome; it was then I began to truly accept the diagnosis.

  

Cause of Nondisjunction Trisomy 21

 

(This is the part of the post that seriously starts to nerd-out, so bear with me).

 

Rather than try to narrate the entire process which results in Down syndrome, I created a few diagrams based on my research. I tried to keep it as simple as possible, because most of us took biology a loooooong time ago (and probably don’t remember much about the following processes). Anyway, the following 3 diagrams depict how reproductive cells (sperm and ova) are formed. The first shows the normal division of the cells, and the next two show division of cells with nondisjunction (which causes Down syndrome).

 

You will see that the determination of Trisomy 21 occurs before fertilization. Researchers have yet been able to determine why this happens, although there is a link with maternal age. Oh, and just in case you forgot, a human should have 46 chromosomes total, 23 from each parent.

Here is how sperm/egg cells are normally produced (colored circles are the cells, and the number inside represents the total number of chromosomes):



It isn't really important for the purposes of this explanation, but notice that in the normal production of sperm cells, 4 gametes (sperm) are produced from the initial parent cell. This is in contrast to ova production, in which only 1 gamete (ovum) and 3 polar bodies (basically junk material) are produced from the parent cell.

These next two diagrams show the production of sperm/egg cells which will result in Down syndrome:



In the above representation, all of the resulting gametes are affected. However, only the ones with the extra chromosomes (24) are likely to produce a viable pregnancy. The child will be affected with Down syndrome.




In the above representation, half of the resulting gametes are affected. Again, only the ones with the extra chromosomes (24) are likely to produce a viable pregnancy and the child will be affected with Down syndrome.



Understand now?

A couple notes I would like to add.... Nondisjunction occurs 85-90% of the time during oogenesis, which means that the majority of Trisomy 21 cases are due to an extra chromosome from the mother. Also, I mentioned below the pictures that the lack of a chromosome would not likely produce a sustainable pregnancy. This is true in regard to the 21st chromosome. However, a pregnancy can be carried full term if the nondisjunction occurs to the 18th chromosome and the gamete with the missing chromosome is fertilized. This is called Turner's syndrome.

So what about the other types of Down syndrome?

Mosaicism occurs after fertilization when the cells begin to divide and multiply. Some of the cell divide normally, and some of them don’t. This results in an individual having some cells with the normal 46 chromosomes, and some with an extra copy of the 21st chromosome.

Translocation, as I mentioned earlier, was the only inheritable type of Down syndrome (although it can occur sporadically as well). When it is inherited, a parent carries a translocated chromosome; in the case of Down syndrome this means one of the chromosomes from the 21st pair is attached to another chromosome, usually the 14th. Even though the chromosome is in the wrong spot, the parent still has the correct number of chromosomes and therefore does not have Down syndrome. However, during meiosis this translocated 21st chromosome is copied along with the 14th into the gamete, which results in Down syndrome. The individual will have a normal pair of the 21st chromosome, and third copy attached to chromosome 14.

I also will point out that all types of Down syndrome affect an individual the same way, and only a genetic test can positively identify which type an individual has.

Phew…. I hope all that makes sense! I apologize for the technical nature of this post, but I wanted to share with those that were curious how Down syndrome actually occurs. Also, if you know someone with Down syndrome or who is about to become a parent of a child with Down syndrome, you will now have some knowledge of the causes.