In a prospective study of 19 pregnancies monitored by amniocentesis at the Center for Human Genetics and the Meyer Rehabilitation Institute, University of Nebraska, Omaha, an adverse outcome was predicted for four fetuses on the basis of low epoxide hydrolase activity (30% of standard). The mothers were receiving phenytoin monotherapy and the infants had clinical characteristics of the fetal hydantoin syndrome. Fifteen fetuses with enzyme activity above 30% of the standard had no features of the syndrome. The authors suggest that this enzymatic biomarker may be useful in the prediction of infants at increased risk for congenital malformations induced by anticonvulsant drugs. 
COMMENT. Anticonvulsant drugs that are metabolized to form oxidative intermediates (epoxides) pose the greatest teratogenic risk to the fetus. The measurement of the enzyme involved with the biotransformation of the epoxide to a less toxic metabolite may serve as a biomarker of the fetus at high risk for the fetal hydantoin syndrome.
The clinical characteristics of the fetal hydantoin syndrome include upturned nose, midfacial hypoplasia, long upper lip, absent cupid's bow, hirsutism of face, back, arms, and legs, nail hypoplasia, hypotonia with delayed motor development, and poor weight gain.