An Eye Opening Genetic Malformation

During the development of an embryo there are many critical processes simultaneously at work , including body axis specification and formation of functional organs. Another important element is the development of the head, arguably the most anatomically sophisticated region of the body. On rare occasions craniofacial malformations will occur, resulting in disorders that have many potential origins, including abnormalities of brain patterning, of the migration and fusion of tissues in the face, and of bone differentiation in the skull.

Holoprosencephaly (HPE) refers to a range of problems involving the malformation of the brain and upper face along the midline. In the most moderate of circumstances, the signs of HPE are as subtle as one single central incisor, shown above on the left. The most extreme end of the spectrum can be associated with midline cleft lip, cyclopia, and an overlying proboscis, shown above on the right. The proboscis, which is the build-up of tissue seen above the eyes, forms because of the obstruction by the central eye. It is made up of frontonasal neural-crest cells that would have normally migrated between the eyes to form the nose and upper lip.

This is extremely rare in live births (~1 in 15,000), but is more commonly detected in early pregnancies (1 in 250); however almost all affected fetuses are miscarried. The cause of these deformities is thought to be due to mutations in the SHH gene. Source of pictures and information: Wilkie et. al (2001) Genetics of Cranofacial Development and Malformation, Nature Reviews Genetics, Volume 2; 458-468.