They found that complete loss of the ALX1 function in these two families seriously disturbed early craniofacial development and resulted in severe frontofacionasal dysplasia, including bilateral extreme microphthalmia, severe facial cleft, complete palate cleft, and low-set posteriorly rotated ears; the frontofacionasal dysplasia in these two families presented in a recessive mode of inheritance. Here, ALX1 is linked to microphthalmia.