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chromosome abnormalities
mental retardation



holoprosencephaly title

Seen in 1.0/10,000 births, holoprosencephaly is a serious brain abnormality usually causing mental retardation and/or death. It arises around 4 weeks after conception, when the developing forebrain fails to undergo normal division into 2 lobes. This area of the brainthe site of intellectual functionis closely linked with midfacial development. The spectrum of facial findings seen with holoprosencephaly includes cyclops (single eye), closely spaced eyes with a single nostril, midline cleft lip and/or a single central front incisor tooth.


bullet Chromosome abnormalities occur in 41% of cases. (Trisomy 13 accounts for about 3/4 of these.) Among those with normal chromosomes, 40% have additional birth defects. 12% of all cases have features fitting recognized syndromes.
bullet Brain abnormalities are classified by the degree of lobar separation. 46% of cases have alobar holoprosencephaly, the most severe form. The proportion is similar in cases with or without chromosome defects or other syndromes. About 20% of all cases are semilobar, 9% are lobar and 25% were not classified.
bullet Severe facial abnormalities are associated with more severe brain findings. However, many children with severe brain abnormalities have mild facial manifestations.


bullet Babies with more severe brain abnormalities are less likely to survive.
bullet 80% of babies with associated chromosome abnormalities die in the first week after birth; 98% die before age 1.
bullet 32% of babies without chromosome abnormalities die in the first week after birth; 70% die before age 1.


Our interview study of pregnancy factors in chromosomally normal babies with holoprosencephaly indicates:

bullet A 10 times higher than normal risk for mothers with insulin-dependent diabetes.
bullet A 4-fold risk increase if the mother smoked cigarettes while pregnant. with an even greater risk if she also drank alcohol.
bullet A 2 times higher risk from medications for respiratory illness and salicylate-containing medications.


One genetic pathway potentially related to holoprosencephaly depends on cholesterol levels. We looked at several genes involved in transporting and regulating fetal cholesterol, but found no differences between affected and normal infants.

holoprosencephaly graph

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