Cause of Kabuki

It is presently known that MLL2  (also known as the KMT2D) genei mutation is responsible for approximately 75% of individuals with Kabuki Syndrome.  More recently, mutations of the KDM6A gene have been discovered in 9% of individuals who tested negative for MLL2 gene mutation. Interestingly, the functions of KDM6A and MLL2 are related to each other.  They function by either adding (in the case of MLL2) an activating methylgroup or removing (in the case of KDM6A) repressive methyl groupsi to specific amino acids in a protein called Histonei H3. The H3 protein can either be modified by repressive (H3K27me3) or active (H3K4me3) methyl groups.  Since the MLL2 and KDM6A genesi have mutations, the MLL2 is not adding the active methyl-groups or KDM6A is not removing the repressive groups.  In essence, although they are doing the opposite activity, the result is the same – repressing (closed chromatini) the open chromatin state of the H3 protein. As a result, the cells in the body that require gene activation through H3 protein, must  now do without. 

To help families better understand the basics of the discovery please see Understanding the Genetics of Kabuki and Epigenetics and How it Relates to Kabuki SyndromeIt is speculated that Kabuki is a heterogeneous syndrome, meaning that multiple genes could potentially be involved. It is hoped that with continued analysis, other genes will be discovered.


It had been initially suggested that Kabuki has a prevalence of 1 in 32,000 live births. However, a number of succeeding studies have thrown some question on this number. It is speculated that Kabuki could be as common as 1 in 10,000 live births.
Kabuki is found equally in males and females.


Present data on Kabuki syndrome does not point to a shortened life span. Many of the medical issues arise early in the child's life and can often be resolved with medical intervention. However, since the syndrome was only formally discovered in 1981, more longitudinal follow-up of individuals will be necessary before we can fully understand typical lifespan for someone with Kabuki Syndrome.