In four of nine EHMT1 mutation-negative patients with core features of Kleefstra syndrome-1 (OMIM #610253) but otherwise heterogeneous phenotypes, Kleefstra et al. [41] identified variants in four functionally related genes, such as KMT2C, methyl-CpG-binding domain protein 5 (MBD5), SWI/SNF Related BAF Chromatin Remodeling Complex Subunit B1 (SMARCB1), and nuclear receptor subfamily 1 group 1 member 3 (NR1I3). This evidence concerns the gene MBD5 and Kleefstra syndrome.