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.
What are the symptoms?
Symptoms change over time. Generally, low muscle tone is noted at birth, and developmental milestones are severely delayed. Most affected children get frequent and severe respiratory infections and have problems with congestion that may be diagnosed as asthma. Seizures may begin in early childhood or early in adolescence. Seizures are often difficult to control with medication, frequently include atonic drop seizures, and change over time. Feeding difficulties and constipation or pseudo bowel obstruction are also common. Severe intellectual disability is typical, with some features of autism present. For more information see About the MECP2 Duplication Syndrome
My 21-year old son diagnosed with MECP2 duplication syndrome started to have atonic drop seizures about 10-months ago. A 3-day EEG video study revealed seisure activty which was labeled Lenox Gaustaut Syndrome. In addition to drop seizures, about 8-times in a 24-hour period he will scream, stiffen up and shake for up to 20 seconds. It takes him about a 90 seconds to recover, catch his breath and relax. How do we know if these bouts are deep brain seizures or if the screaming is him in pain. Should we get a MRI? I can’t get the neurologist to call us back. My son does not tell us how he feels. Thank you,
Hi Dakota’s Mom, I am not a doctor and can’t give you medical advice, but our son Dave who has MECP2 Duplication Syndrome also has similar seizures. Many individuals with MECP2 Duplication Syndrome have atonic seizures and an overall pattern that some neurologists call Lennox-Gastaut and others say is different in some ways from Lennox-Gastaut… Whether this Lennox-Gastaut label is used is more a difference in terminology and doesn’t really matter to much beyond that. The other episodes that you describe are more difficult to interpret. Did Dakota have any of these during his 3-day EEG? If so, that might help to sort out whether this is seizure activity or something else, especially if they did video with the EEG. Beyond that, all I can say is that what you describe is similar to several things that have been described in other MECP2 Duplication boys and girls. Some, including our son, have had seizures that fit this general description. Some also seem to grab their chest and look distressed or hurt at times and the exact nature of it has been hard to track down. Some of these episodes may be GERD. Some people experience sudden sharp pain from resulting from stomach acid coming up into sensitive areas of the esophagus. If Dakota really stiffens for a an extended period, it may be a tonic seizure. As far as doing an MRI goes, it may be helpful in general but it is unlikely to give a clear answer to what the episodes you describe really are. Has Dakota had an MRI before? If he has, having one now may indicate the amount of changes occurring. If not, it will probably show some atypical findings but in most cases of which I am aware that involve individuals with MECP2 duplication, it has not indicated a specific focal area for the seizures. In any case, I would recommend discussing the episodes you describe with your son’s neurologist when you can and also with his general physician who may have some other ideas about what could be causing these episodes.