Repeated Neural Tube Defects and Valproate Monotherapy Suggest a Pharmacogenetic Abnormality


Address correspondence and reprint requests to Dr. E. Andermann at Neurogenetics Unit, Montreal Neurological Hospital and Institute, McGill University, 3801 University St., Montreal, Quebec H3A 2B4, Canada.


Summary: Valproate (VPA) is an effective, widely used antiepileptic drug. Unfortunately its use in pregnant women is associated with neural tube defects in the offspring. Although the etiology of neural tube defects is multifactorial, there is evidence that underlying genetic susceptibility plays a part. We describe two women taking moderate doses of VPA who repeatedly bore children with neural tube defects, despite folate supplementation. This suggests a pharmacogenetic susceptibility to the teratogenic effects of VPA.