A de novo mutation was detected in an unknown protein domain of EHMT1 the causal gene in Kleefstra syndrome, compound heterozygous variants inherited in trans were observed in SRCAP which was recently associated with Floating-Harbor syndrome, two individuals showed compound heterozygous mutations in BBS2 which causes Bardet-Biedel syndrome, a fifth individual displayed compound heterozygous mutations in NOTCH2 which causes Alagille syndrome, and a sixth individual displayed a compound heterozygous mutation in KMT2D the locus implicated in Kabuki syndrome. Here, NOTCH2 is linked to Kleefstra syndrome.