The first step to understanding MECP2 duplication syndrome

Just this year, after seven years of not knowing what was going on with our daughter, we were told that she most likely has a very rare genetic disease called MECP2 Duplication Syndrome, a recently discovered neurodevelopmental disorder with severe effects. They gave us test results and articles full of explanations with a lot of medical terminology. If you are not a medical professional, you will not understand a word of these results and reports. So, I did some research and now I have a basic understanding of genetic diseases like MECP2 duplication syndrome. As the title suggests, this is only the first step in understanding this disease and will only cover a basic genetic aspect. Stay tuned for future articles that I plan to delve further into with MECP2 and its specific effects.

To have any kind of understanding about any genetic disease, we must understand basic genetics, so let’s jump right in. A lot of this was covered in seventh grade biology, but stick with me, I’m going somewhere with this. We know that our bodies are made up of cells. Inside those cells there are many things, but the most important thing is the “control center” called the nucleus. It is very important because it acts as the “brain” of our cells. Now inside the nucleus is our DNA, or more specifically our hereditary material. DNA can be broken down into thread-like structures known as chromosomes. Just as the cell has a nucleus, each chromosome has something called a centromere, but instead of its “brain,” it is a constriction point. The centromere divides the cell into two sections and gives each chromosome its unique shape (such as x or y). The sections of a chromosome are called “arms.” There is a shorter arm on each chromosome called the “p” arm and a longer arm on each chromosome called the “q” arm.

There are 23 pairs of chromosomes in each person’s cells, and one of those pairs determines whether we are male or female. Females have two “x” chromosomes and males have one “x” and one “y”. Because females have two “x” chromosomes, during fetal development one of these x’s will randomly inactivate (stop working). Since it is random as to which x is inactive in each cell, you could have many cells with the x that your mother gave you active, and many cells with the x that your father gave you active.

Our genes are hereditary material found on our chromosomes. They act as instructions for making molecules called protiens. In addition to the “p” arm and the “q” arm, these genes can be located at various points on the chromosome. The MECP2 gene is located on the x chromosome in the long “q” arm at point 28. So if your doctor tells you something about an xq28 chromosome, they are talking about the MECP2 gene. What happens in genetic disorders is that genes are found to have mutations (which just means a change in the genetic makeup of a normal gene). There may be deletion mutations in which parts of the gene are missing, or there may be duplication or even triplication mutations in which exact small copies of part of the gene are found.

As for the MECP2 gene, if there is a deletion mutation in that gene, most of the time it results in Rett syndrome. If there is a duplication or triplication mutation, it usually results in MECP2 duplication syndrome. Rett syndrome mainly affects girls, because male fetuses with a deletion mutation in this gene generally do not reach term. MECP2 duplication syndrome mainly affects boys, because girls who have a duplication mutation in this gene generally show no symptoms because that is the x that is inactivated during the x inactivation period during fetal development. We found that sometimes the duplication of this gene can be moved to another chromosome, so inactivation of x is not helpful for these girls. MECP2 duplication is very difficult for children. The reason is that they only have one x, so the duplication is present in every cell in their bodies. Most boys with MECP2 have much more severe symptoms than girls (although not always, we know that some girls have the same severe symptoms as men, this is due to the aforementioned translocation). Symptoms include hypotonia (floppy baby syndrome), severe mental retardation, poor speech development, progressive spasticity, recurrent respiratory infections, seizures, autistic behaviors, and gastrointestinal disorders. It can also cause neurological deterioration that can quickly lead to premature death.

As you can see, this is a very serious disease and we all need to raise awareness. This has been only the first step in understanding what this disease is, but there is much more to learn and discover. Support research on MECP2 and Rett syndrome, and tell people you know about this debilitating disorder so that we can all fight for a cure.