Deletions spanning theMN1gene (22q12.1) have recently been proposed as playing a role in craniofacial abnormalities that include cleft palate, as mouse studies have demonstrated thatMn1haploinsufficiency results in skull abnormalities and secondary cleft palate. We report on four patients (two families) with craniofacial abnormalities and intellectual disability with overlapping microdeletions that span theMN1gene. Comparative genomic hybridization microarray analysis revealed a 2.76 Mb deletion in the 22q12.1 region, in three family members (Family 1), that contains theMN1gene. In addition, a complex 22q12 rearrangement, including a 1.61 Mb deletion containing theMN1gene and a 2.28 Mb deletion encompassing theNF2gene, has been identified in another unrelated patient (Family 2). Based upon genotype-phenotype correlation among our patients and those previously reported with overlapping 22q12 deletions, we identified a 560 kb critical region containing theMN1gene that is implicated in human cleft palate formation. Importantly,NF2was also found within the 22q12 deletion region in several patients which enabled specific clinical management for neurofibromatosis 2. © 2015 Wiley Periodicals, Inc.