Holoprosencephaly develops very early in pregnancy, often before a person knows they are pregnant. At ~3 weeks in human pregnancy (i.e. 5 weeks from the last menstrual period), key structures form that send signals to guide the correct formation of the brain, including setting up what will be the future forebrain and directing the division of the hemispheres. Since the molecular processes that guide forebrain separation also drive correct patterning of the face, holoprosencephaly is commonly accompanied by facial defects.
It is the failure to establish the frontal midline that can explain the disease manifestations, as the body is unable to distinguish the left and right halves. This impairs the correct formation of paired midline structures such the forebrain hemispheres and eyes, as well as other midline structures such as the nose and mouth, and explains why we observe defects such as closely spaced eyes, a cleft lip or palate, and a single front tooth.
Mutations in genes can interfere with these early signals. Currently, 14 different genes have been linked to Holoprosencephaly, including the ZIC2gene. When the ZIC2gene does not work properly, it can affect how the brain is organized during these early stages of development. Holoprosencephaly can also be caused by changes in chromosomes or as part of a genetic syndrome.
ZIC2