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. We were given test results and papers full of explanations with a lot of medical terminology. If you’re not a medical professional, you’re not going to understand a word of these results and reports. So, I did a little digging and now have a basic grasp on genetic diseases like MECP2 Duplication Syndrome. As the title suggests, this is just the first step to understanding this disease and will only cover a basic genetic look. Be on the lookout for future articles where I plan to go more in depth with MECP2 and it’s specific effects.
To have any kind of understanding about any genetic disease, we must understand basic genetics, so let’s jump right in. Much 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 are a lot of things, but the most important thing is the “control center” called the nucleus. It is so important because it acts like 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 like the cell has a nucleus, each chromosome has something called a centromere, but rather than the “brain” of it, it is a constriction point. The centromere divides the cell into two sections, and gives each chromosome it’s unique shape (like x or y). The sections on 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 determine 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’s random as to which x inactivates in each cell, she could have many cells with the x her mother gave her active, and many cells with the x her father gave her active.
Our genes are hereditary material that are located on our chromosomes. They act like instructions to make molecules called protiens. In addition to the “p” arm and “q” arm, these genes can be located at number points assigned to the chromosome. The MECP2 gene is located on the x chromosome on the long “q” arm at point 28. So if your doctor ever says anything to you about an xq28 chromosome, he or she is talking about the MECP2 gene. What happens in genetic disorders is that the genes are found to have mutations (which just means a change in the genetic structure from a normal gene). There can be deletion mutations where pieces of the gene are actually missing, or there can be duplication or even triplication mutations where tiny exact copies of some of the gene are found.
In regards to the MECP2 gene, if there is a deletion mutation on that gene, it most often results in Rett Syndrome. If there is a duplication or triplication mutation, it usually results in MECP2 Duplication Syndrome. Rett syndrome mostly affects girls, because male fetuses with a deletion mutation on this gene usually don’t make it to full term. MECP2 Duplication syndrome mostly affects boys, because girls who have a duplication mutation on this gene usually don’t show symptoms because that is the x that gets inactivated during the x-inactivation period during fetal development. We are finding that sometimes the duplication on this gene can translocate to another chromosome, so x inactivation is not helpful for these girls. MECP2 Duplication is really hard on boys. The reason is that they only have one x so the duplication is present in very cell of their bodies. Most boys with MECP2 have much more severe symptoms than girls (though not always, we do know some girls with the same severe symptoms the males get, this is due to the translocation mentioned above). 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 neurologic deterioration which can quickly lead to early death.
As you can see, this is a very serious disease and we all need to raise awareness. This has just been the first step in understanding what this disease is, but there is much more to learn and discover. Please support MECP2 and Rett Syndrome research, and tell people you know about this debilitating disorder so we can all fight for a cure.