Repeated neural tube defects and valproate monotherapy suggest a pharmacogenetic abnormality.
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.
Duncan
S
S
Neurogenetics Unit, Montreal Neurological Institute and Hospital, McGill University, 3801 University Street, Montreal, Quebec H3A 2B4, Canada.
Mercho
S
S
Lopes-Cendes
I
I
Seni
M H
MH
Benjamin
A
A
Dubeau
F
F
Andermann
F
F
Andermann
E
E
D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects* / Q000378:metabolism / Q000627:therapeutic use; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D020073:Gravidity / Q000235:genetics; D006801:Humans; D009436:Neural Tube Defects / Q000139:chemically induced* / Q000235:genetics; D010597:Pharmacogenetics; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy*; D011256:Pregnancy Outcome / Q000235:genetics; D014635:Valproic Acid / Q000009:adverse effects* / Q000378:metabolism / Q000627:therapeutic use
D000927:Anticonvulsants; D014635:Valproic Acid