Kabuki Syndrome Network in Japan Newsletter歌舞伎ジャーナル 第３１号
There has been some discussion again on the topic of how Kabuki is diagnosed and whether or not there is a 'blood test' to confirm diagnosis.
I'd like to clarify:
There is no definitive test for diagnosing Kabuki - yet. Geneticists must rely strictly on presenting characteristics. The criterium for diagnosis is usually that the child must have four of the following five cardinal manifestations:
4)mental retardation (intellectual disability)
The characteristic facies is imperative.
Associated features, which are also looked at but which are not cardinal manifestations:
1)neonatal hypotonia and feeding difficulties
3)congenital heart defects
5)small mouth, micrognathia (smallness of the jaws), cleft/high arched palate, hypodontia (missing teeth)
7)early breast development
Dr. Milunsky has presented a study in which 6 children all had a duplication on chromosome 8p22-8p23.1 and an inversion at 8p23.1. All mothers of these 6 children also had the inversion at 8p23.1.
Please go to http://www.kabukisyndrome.com/files.html to read further.
In speaking to him recently, there are now 13 families on which the studies have been completed on - all showing the same results. There are now about 80 families which are participating in his study - from Australia, Japan, France, Belgium, Canada, and the USA, just to name a few. Dr. Milunsky was very appreciative of the many families who are participating and is always looking for more.
They have found that all the children have the same area affected (8p22-23.1). To further add to the excitement of their findings, they're discovering some have a greater proportion of this area duplicated than others. So to better understand, if the 8th chromosome were divided into A-Z areas and all children in his studies have the C-G area duplicated....some may have only C-E duplicated, others may have D-G duplicated....but ALL remain in the same C-G zone. I asked him if it's true that the greater the area (say the entire C-G zone), the greater the disabilities? He said no, that's not the case because some genes can be duplicated and not have an effect on the person, others do.
He said that they continue to look with greater detail at the genes in this duplicated area to better understand the syndrome.
Dr. Milunsky said that his findings must be consistent with many more families before it is ready to go to the clinical setting. In other words, they, along with other researchers, need to consistently get similar results before it can become a diagnostic tool for Kabuki. I think we can all imagine how traumatic it would be to diagnose children based on genetic testing of blood samples, only to find out later that the testing was not accurate.
I asked Dr. Milunsky if they knew what percentage of the general female population has an 8p23.1 inversion that do not have children with Kabuki? This is important to know to calculate the percentage of chance a person with an 8p23.1 inversion has of having a child with Kabuki. Because, of course, if my other girls also have the same 8p23.1 inversion I have, it would be very helpful if they could get relatively accurate genetic counselling. Unfortunately, though, he said this is not yet known. But he said these are all questions that future studies will answer.
In regards to whether Dr. Ming is exclusively studying the exact same region of the chromosome as Dr. Milunsky, I don't know. I do know that he is also studying the etiology of Kabuki and it is therefore important for us to participate in his study also. I certainly like the idea that a handful of scientists are looking for the cause of Kabuki.
It's important we don't participate in these studies looking for a diagnosis for our child, but instead to give the researchers an opportunity to understand this syndrome at a genetic level. Here is an opportunity for all of us to make a difference!
Hope this helps to clarify!