What are the genetic changes related to Kabuki syndrome ?
Kabuki syndrome is caused by mutations in the KMT2D gene (also known as MLL2) or the KDM6A gene.  Between 55 and 80 percent of cases of Kabuki syndrome are caused by mutations in the KMT2D gene. This gene provides instructions for making an enzyme called lysine-specific methyltransferase 2D that is found in many organs and tissues of the body. Lysine-specific methyltransferase 2D functions as a histone methyltransferase. Histone methyltransferases are enzymes that modify proteins called histones. Histones are structural proteins that attach (bind) to DNA and give chromosomes their shape. By adding a molecule called a methyl group to histones (a process called methylation), histone methyltransferases control (regulate) the activity of certain genes. Lysine-specific methyltransferase 2D appears to activate certain genes that are important for development.  About 6 percent of cases of Kabuki syndrome are caused by mutations in the KDM6A gene. This gene provides instructions for making an enzyme called lysine-specific demethylase 6A. This enzyme is a histone demethylase, which means that it helps to remove methyl groups from certain histones. Like lysine-specific methyltransferase 2D, lysine-specific demethylase 6A regulates the activity of certain genes, and research suggests that the two enzymes work together to control certain developmental processes.  The KMT2D and KDM6A gene mutations associated with Kabuki syndrome lead to the absence of the corresponding functional enzyme. A lack of the enzymes produced from these genes disrupts normal histone methylation and impairs proper activation of certain genes in many of the body's organs and tissues, resulting in the abnormalities of development and function characteristic of Kabuki syndrome.  Some people with Kabuki syndrome have no identified KMT2D or KDM6A gene mutation. The cause of the disorder in these individuals is unknown.