Although no functional studies were performed, both these patients had variants in other genes that were also predicted to be damaging, such as in GLI2, which has been reported to be involved in holoprosencephaly and abnormal pituitary development (30), and in BMP4, which has a crucial role during embryonic pituitary development (31), indicating that variants in one or more genes other than FAT2 and DCHS2 may be required for an apparent phenotype. This evidence concerns the gene FAT2 and holoprosencephaly.