Holoprosencephaly as a possible embryonic alcohol effect

Am J Med Genet. 1991 Aug 1;40(2):151-4. doi: 10.1002/ajmg.1320400206.


Three mothers of infants with holoprosencephaly consumed alcohol heavily in pregnancy. We postulate that early alcohol exposure is a possible cause of their malformation. The 3 mothers consumed alcohol only in the first trimester but the first mother continued to take chlordiazepoxide and imipramine throughout the pregnancy. Her infant had an alobar holoprosencephaly associated with a median cleft lip, ocular hypotelorism, and a flat nose. The other infants had semilobar holoprosencephaly and hydrocephalus. These latter 2 infants did not show the characteristic facies of the fetal alcohol syndrome. G-band chromosome studies were normal in all 3 infants. The association of holoprosencephaly with alcohol exposure during pregnancy in humans has been mentioned only briefly, although this malformation has been induced by alcohol in animals. These 3 infants may support the hypothesis that acute or subacute heavy alcohol exposure early in pregnancy could lead to holoprosencephaly without the necessity of a chronic alcohol exposure and without necessarily causing the typical facial findings of the fetal alcohol syndrome.

MeSH terms

  • Abnormalities, Drug-Induced*
  • Alcohol Drinking / adverse effects*
  • Chlordiazepoxide / therapeutic use
  • Female
  • Holoprosencephaly / chemically induced*
  • Holoprosencephaly / diagnostic imaging
  • Humans
  • Imipramine / therapeutic use
  • Maternal-Fetal Exchange
  • Pregnancy
  • Smoking
  • Ultrasonography


  • Chlordiazepoxide
  • Imipramine