VALPROIC ACID EMBRYOPATHY

Abstract

We describe three children born to an epileptic woman who received carbamazepine (CBZ) and methosuximide (MT) during one pregnancy and valproic acid (VPA) and CBZ during the other two pregnancies. The children exposed to VPA and CBZ showed craniofacial abnormalities including prominent forehead, epicanthal folds, hypoplastic zygomatic arches, shallow philtrum, depressed nasal bridge, posterior angulation of the ears and infraorbital creases while the child exposed to only CBZ and MT did not. In addition to the previously described features, both patients exposed to CBZ and VPA had lateral displacement of the medial origin of the eyebrows and a carrying angle of zero degrees. One of them also had hypoplastic nails and teeth. This unique family enabled us to compare sibs with the same parents who were exposed to a different combination of antiepileptic drugs and evaluate potential teratogenic effect. The findings in this family would support the previous observation that valproic acid may be associated with a pattern of dysmorphic features in addition to the 1-2% risk for neural tube defect it is known to have when taken during the early part of pregnancy.