Genetic Basis for Brain Malformation Found

According to research results scheduled to be published in the February 1, 2007 issue of the Federation of American Societies for Experimental Biology Journal, a mutation of the TG interacting factor (TGIF) gene, specifically known as TGIF.P63R, is responsible for holoprosencephaly, which may result in severe malformations of the brain and skull. In particular, researchers found that this mutated (transformed) gene does not produce the protein necessary for normal development but may actually destroy the small amounts of the normal protein that is required for normal development.

Holoprosencephaly (HPE) is a relatively rare birth (~ 1:16,000 live births) defect that can result in brain and facial defects ranging from mild dental abnormalities to severe changes in brain anatomy that usually lead to death in the 1^st month of life. According to information prepared by the Carter Center at Stanford University there are 4 major subclasses of HPE (in decreasing order of severity).

Alobar HPE is by far the most severe form. In this variant the brain does not divided into the right and left hemispheres (sides) and there are severe abnormalities of both the brain (single ventricle surrounded by a thin layer of normal brain tissue) and facial structures (only a single eye is present, a condition known as cyclopia; the nasal bones are absent or malformed and only a single nostril, termed a proboscis, is present, sometimes cleft lip and cleft palate are also present, and there may be abnormalities of the teeth).

In Semi-Lobar HPE the brain is partially divided and there are some additional moderate abnormalities such as two hemispheres in the rear but not the front of the brain (partially-divided cerebral hemispheres).

Lobar HPE is a milder variant where the brain is usually normally divided but there are abnormalities such as fusion of some brain sub-structures.

The Middle Interhemispheric Variant (MIHV) of HPE is where the middle structures of the brain (posterior frontal and parietal lobes) are not well separated.