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 1st 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.
As mentioned above, HPE (in one variant or another) is present in about 1:16,000 live births. However, Alobar or Semi-Lobar HPE is found in approximately 1:250 of spontaneous first trimester abortions. This suggests that there are far more cases of HPE conceived that are not consistent with extra-uterine life and are discarded by the body via some process that is currently poorly understood.
It is currently thought that only 3 % of fetuses with HPE survive until birth and that most of those will die within 6 months. Some degree of mental retardation is usually found among survivors. In addition to the specific signs of HPE previously listed, there are often other systemic malformations present including heart defects and abnormalities of the digestive and urinary systems.
In many cases of HPE there are no specific chromosomal abnormalities that can be identified in utero or after delivery. With the widespread use of prenatal ultrasonography, many cases of HPE are identified at an early-enough gestational age to allow elective termination of the pregnancy. Sadly, the areas of the brain that control movement and heart rate are unaffected by the malformation of the “higher brain centers” and thus lead to a normal pregnancy with a profound psychological trauma at birth.
Since there is no reported evidence of any effective prenatal therapy such as dietary supplementation with vitamin compounds or folic acid (as is the case with neural tube defects), the optimum strategy for preventing HPE will require that women who are planning a pregnancy or are of childbearing age must take every possible step in avoiding exposure to known or suspected mutagenic agents, particular in the first trimester (13 weeks).
As mentioned in the previous paragraph, there is no known therapy (dietary or otherwise) that will reduce the chances or severity of HPE there is a growing body of evidence that a healthy lifestyle can reduce the incidence of other forms of fetal and infant pathology. In the absence of any information to the contrary, fresh foods and an exercise program should be an integral part of routine prenatal care.
For More Information
The Carter Centers for Brain Research in Holoprosencephaly and Related Malformations are located at the Texas Scottish Rite Hospital for Children in Dallas, Texas; Kennedy Krieger Institute in Baltimore, Maryland; Stanford University at Stanford, California; Rutgers, the State University of New Jersey in Newark, New Jersey; and the National Institutes of Health in Bethesda, Maryland. The Centers’ main pages can be found at http://www.stanford.edu/group/hpe/.
Wikipedia contributors: Cyclopia. Wikipedia, The Free Encyclopedia. January 17, 2007, 21:42 UTC. Available at: http://en.wikipedia.org/wiki/Cyclopia. Accessed January 18, 2007.
Ferrand, N; Demange, C; Prunier, C; Seo, SR and Atfi, A: A Mechanism for Mutational Inactivation of the Homeodomain Protein TGIF in Holoprosencephaly.
FASEB Journal 21 (2) February 1, 2007 (In Press).
Plawner LL, et al. Neuroanatomy of Holoprosencephaly as Predictor of Function: Beyond the Face Predicting the Brain. Neurology, 59:1058-1066 (2002).
The information presented in this article and its included links is of an informational nature only and is not intended as a recommendation of any changes in the reader’s health care program. Before making any changes in diet, medications, or other treatments the reader is strongly advised to consult with their health care provider.