Letter to the Editor: Discordant twins for neural tube defect on treatment with sodium valproate

Dear Sir, Neural tube defects are reported to be commoner in women treated with sodium valproate than in women without epilepsy and higher doses carry an increased risk1–5. The mechanisms are unknown. I would like to report a twin pregnancy in a woman treated with sodium valproate in which one of discordant twins had a neural tube defect. She was a 28 year-old lady with idiopathic generalized epilepsy starting at the age of 19 years with tonic–clonic seizures but no absences or myoclonus. An EEG had shown photogenic discharges. Phenobarbitone and phenytoin had been ineffective but her seizures were abolished with sodium valproate 1000 mg daily 3 years earlier. A previous pregnancy when treated with sodium valproate was uncomplicated. Her father had myoclonic epilepsy. She had a twin pregnancy in which her daughter had spina bifida with meningomyelocoele and hydrocephalus and her son was unaffected. She was not treated with folate before or during the pregnancy. As both twins will have been exposed to the same concentrations of sodium valproate in utero the main determinant of the abnormality is likely to be genetic. Discordant twins for neural tube defects have been described in a review of 363 patients in which seven pairs were found6. None of the mothers had been treated with sodium valproate. Epilepsy was more commonly found on the maternal side but in this case her father had epilepsy. It is unclear whether the presence of a generalized epilepsy syndrome and/or the paternal inheritance contributes to the risk. The mechanism is likely to be complex with an interaction between major genetic factors, as yet unidentified, enhanced by exposure to higher doses of valproate in early pregnancy.