Kleefstra syndrome is a rare genetic disorder (MIM #610253, Orpha:261494). The cause was found first to be a deletion in the region 9q34.2 with the main gene EHMT1, which is a histone methyltransferase and involved in epigenetics, namely histone methylation on histone H3 lysine residues. It also methylates DNA. Similar phenotypes were later found with loss of function mutations in other proteins involved in histone methylation, namely KMT2C (MLL3) located on 7q36.1, MBD5, SMARCB1, and NR1I3 (MIM #617768 Kleefstra syndrome 2).