Heterozygous pathogenic variants in SIX3 are associate with holoprosencephaly.[71] The second CNV was a duplication at chr22q11.21 (chr22:19744894–19758306, 13.4 kb) and encompassing TBX1, which is considered to be responsible for features velocardiofacial syndrome in the presence of haploinsufficiency.[72] Duplication of chr2p21 or chr22q11.21 is not known to be associated with a phenotype. Here, SIX3 is linked to holoprosencephaly.