What is a Gene duplication?
By analogy, we can imagine a set of chromosomes as a complete set of instructions for constructing an individual. Each chromosome is like one volume in a 46 volume set. In order to keep our place we designate specific areas of each chromosome. So Xq 28 identifies a chapter near the end of the long arm of the X chromosome and genes are like words made up of bases that are sort of like the letters that make up the words. (it may help to point out that following this analogy, genetic words are quite long- the MeCP2 gene would have about 75,000 letters if it were a word). Now imagine that you are trying to follow a recipe in this book exactly and exactly and there is a misprint:
Add one egg, an eighth of a teaspoon of salt, exactly one level teaspoon of MeCP2, shake vigorously, add one egg, an eighth of a teaspoon of salt, exactly one level teaspoon of MeCP2.
Somehow part of the instructions were duplicated and if we follow the recipe exactly, this could cause a problem. In most cases of MECP2 Duplication syndrome the duplication is on the X Chromosome. In some cases a small part of extra genetic material from the X chromosome is attached to one of the other chromosomes. The effects appear to be the same.
Do longer duplications present more severe symptoms?
This doesn’t seem to be the case. Individuals with long duplications of 20 or more genes seem to have relatively similar effects to individuals with shorter duplications of just a few genes. The critical thing seems to be the duplication of the MECP2 gene, hence the name of the syndrome.
Can there be more than one duplicate copy of the MECP2 gene?
Some individuals actually have triplication or three copies of the gene on the same X chromosome. Although these cases are rare and it is hard to form general conclusions, triplications appear to be associated with particularly severe symptoms.
Is MEPC2 Duplication syndrome a male version of Rett syndrome?
Sort of… but not really. The MEPC2 gene is involved in both Rett syndrome and MePC2 Duplication syndrome, but it is involved in a different way. Some of the features associated with Rett syndrome are also seen in MeCP2 Duplication syndrome, but some are different. So it’s fair to say there are similarities and connections, but they are actually separate and unique conditions.
Is MECP2 Duplication syndrome a rare condition?
Currently, diagnosed cases remain rare, but its rarity seems to be due mostly to the fact that the vast majority of cases go undiagnosed. That will no doubt change drastically in the next 5 or 10 years. With more testing many more cases will be diagnosed. As of June 2011, there are probably more than 1,000 cases diagnosed worldwide. The exact number is unknown because diagnostic testing has become available at many different sites and no central data collection counting diagnosed cases. It is hard to estimate how common it will become as diagnostic testing becomes more frequent. It will probably remain a lot less common than Fragile-X or Down syndrome. Based on available information my very rough guess is that it will be found in about 1 out of every 10,000 or 20,000 live births of boys. Of course, this only a semi-educated guess and the actual numbers could turn out to be a lot higher or a lot lower.
Can girls have MECP2 Duplication syndrome?
Yes, but it is much rarer in girls than in boys. Since females have two X chromosomes, they can normally “turn-off” or “inactivate” the one that is creating a problem and use the other one. When that happens, the girl is a carrier who has no obvious signs of the condition. Since boys have only one X and females have two, females normally inactivate on X in each pair. We might expect that one of each pair of Xs is randomly chosen, but the X with the duplication is normally selected for shutdown. In rare cases the extra copy of the MECP2 gene is not on the X but becomes attached to another chromosome. This can happen to boys or girls. Since it is not on the X chromosome, X inactivation does not help with this problem and both girls and boys experience the problems associated with MECP2 duplication.
When was MECP2 Duplication Syndrome first discovered?
MECP2 Duplication Syndrome is a relatively recent discovery. In 1999, Lubs and colleagues identified an X-linked syndrome with hypotonia (low muscle tone), progressive central nervous system deterioration, sever intellectual disability, an other features now associated with MECP2 Duplication Syndrome. The syndrome was more completely described in 2005 by in articles by Meins and colleagues and by Van Esch and Colleagues.
What is the life expectancy of children with MECP2 Duplication syndrome?
This question is more complicated than it appears to be. The syndrome has only recently been discovered and it is usually diagnosed in young children. Clearly, infectious disease is a major threat for these children. Based on about 120 cases that have been described in the literature, about half survived beyond the age of 12. However, a significant number reach adulthood and at least one individual in his 40s has been described. More time and more information will be required to develop better estimates. Hopefully, as more is learned about the health care needs of these individuals, the prospects for a long life will improve.