INHERITANCE

The cause of Kabuki is still unknown. It seems to be a sporadic mutation, in the genetic makeup of the individual. It's not suspected that Kabuki Syndrome is linked to any external or environmental conditions or circumstances. There are a few rare cases of children and one parent having Kabuki. This leads geneticists to believe that it's an autosomal dominant syndrome. This means that an individual with Kabuki has a 50% chance of passing the syndrome on to their child.

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:

1)characteristic facies

2)skeletal anomalies

3)dermatoglyphic anomalies

4)mental retardation (intellectual disability)

5)short stature

The characteristic facies is imperative.

Associated features, which are also looked at but which, are not cardinal manifestations:

1)neonatal hypotonia and feeding difficulties

2)recurrent infections

3)congenital heart defects

4)reno-urinary malformations

5)small mouth, micrognathia (smallness of the jaws), cleft/high arched palate, hypodontia (missing teeth)

6)obesity

7)early breast development

8)deafness

For some syndromes, chromosomal studies will confirm a diagnosis. Chromosomal studies will show if there are any irregularities with the 23 pairs of chromosomes we all should have in every one of our cells. Is there a section of a chromosome missing? (too little information). Is there an extra part of a chromosome? (too much information). These kinds of irregularities will show themselves with certain syndromes - Down syndrome being one of them. However, many conditions or syndromes do not show any irregularities in the chromosomal studies - that is, all 23 pairs appear normal. For some syndromes, this is because the deletion or irregularity lies in the gene (remember, each chromosome consists of thousands of genes!) So, suddenly we need much more sophisticated equipment to detect such micro (small) deletions. It's only very recently that scientists are beginning to be able to see such deletions. But in the case of Kabuki we do not know where the defect is. Where do they begin to look?

The Human Genome Project is now complete in that they have isolated and identified all 30,000 genes. That is the beginning - being able to identify and name each gene. But it's still a long ways from knowing what each gene is responsible for. Keep in mind that it's only been about 30 years that we've even been able to see chromosomes, let alone genes!

Again, just because the chromosomes don't show an abnormality, the genes may. And these micro deletions on the genes likely cause varied abnormalities to appear or show themselves in the body. It is widely believed by geneticists that all humans have 6 or 7 defective genes. However only certain ones and/or certain quantities will manifest into a syndrome or condition. Therefore many conditions such as being prone to headaches, obesity, depression, etc, have a genetic basis - we just don't know where the defect lies.

And so, because Kabuki (and many other syndromes) must still be diagnosed based on the physical characteristics, listed above, diagnosis is difficult. Often the characteristics of Kabuki syndrome become more obvious as the child becomes older.

Another informative read about chromosomes and genes.......

http://home.wxs.nl/~avbetuw/raveneng.htm

Occurrence of Kabuki in Japan vs. non-Asians

It's reported on several home pages of Kabuki and in older genetic articles that Kabuki is far more common in Japan than anywhere else. This is NOT true.

The reason there were so many children diagnosed with Kabuki, initially, in Japan was two-fold:

First, it was initially described there. Therefore the primary search for other children with similar characteristics occurred there.

Second, many (most?) children in Japan who have special needs go to separate schools. The search for other children with Kabuki was therefore simplified and many were diagnosed in a relatively short period of time.

Gradually, as genetic articles are written on this newly described syndrome, more and more geneticists learn of it. This takes time. The typical presenting characteristics are gradually being better understood. There are still many questions, such as: When a child presents with, say, hypoglycemia - is that typical for the syndrome or is it completely unrelated? This is one of the reasons all the characteristics discovered are reported in the published articles. Gradually, the geneticists (and other professionals) get a better understanding of what Kabuki entails.

Recurrence Risk

Parents often wonder what the chances are that they could have another affected child. If neither of the parents are affected (the majority of the time), then this most likely represents a new/sporadic mutation in this child only (in the one egg or sperm that conceived him/her) and the recurrence risk is very low.