Valproate Embryopathy, Susceptibility To

All antiepileptic drugs are potential teratogens. Anticonvulsant treatment during pregnancy presents the challenge of balancing between optimal treatment for seizure control and possible harmful fetal effects. One of the best delineated examples of harmful fetal effects is the fetal valproate syndrome (FVS), comprising typical facial features, developmental delay, and a variety of malformations such as neural tube defects, cardiac and gastrourinary malformations, and limb defects (Winter et al., 1987; Ardinger et al., 1988; Clayton-Smith and Donnai, 1995). Malm et al. (2002) described 3 families in which all offspring, 3 children in 1 family and 2 in each of the other 2 families, were affected by FVS. Malm et al. (2002) published pictures illustrating the facial features of FVS: trigonocephaly, medial deficiency of eyebrows, broad nasal root, anteverted nares, shallow philtrum, and long and thin upper lip.

In males with ornithine transcarbamylase (OTC) deficiency (311250), sodium valproate may precipitate acute liver failure (Tripp et al., 1981). Hjelm et al. (1986) concluded that the vulnerability of toxic effects of valproate extends to heterozygotes as well. They described a family in which 2 daughters and a son died in childhood, all with clinical features suggesting a metabolic disorder; in one, valproate seemed to have accelerated death. They concluded that the mother was a heterozygote for OTC deficiency.