Genetic Factors of Congenital Malformations and Diseases in the Offspring of Women with Epilepsy

We examined the genetic factors that cause congenital malformations and diseases in the offspring of pregnant women with epilepsy. The subjects were 177 offspring of epileptic patients who had been treated in the Department of Neuropsychiatry in Fukushima Medical University Hospital between July 1971 and February 2015. We found congenital malformations and diseases in 25 offspring. There were 12 malformation cases: 4 cleft lip and cleft palate cases, 3 congenital heart defect cases, 1 case of both cleft palate and congenital heart defect, 1 iridocoloboma, 1 hemirenal dysplasia, 1 arachnoid cyst, and 1 syndactylia. The medical situation of those pregnant women is usually monotherapy and the average dose of each antiepileptic drug (AED) is less than other reported cases. There is a possibility that side-effects are down on the appearance of malformation because of low AED dose. AEDs during pregnancy were not used in the arachnoid cyst and syndactylia cases. In 7 of the 12 malformation cases (58.3%), we found the same congenital malformations in first- to third-degree relatives. Moreover, the hemirenal dysplasia case and syndactylia case both had genetic factors of epilepsy with autosomal dominant inheritance in three generations. It is noteworthy that in the iridocoloboma case the husband of epileptic pregnant woman had the same malformation, and in the case of arachnoid cyst the pregnant woman with epilepsy also had the same malformation. The number of congenital malformations was only 3 in 168 cases (1.8%) with no genetic factors of epilepsy and congenital malformation. Disease cases: 10 epilepsy and/or febrile seizure cases, 1 case of sudden death within 6 months after birth, and a case each of autism, Down syndrome, and strabismus. In the strabismus case, we found the same disease in the husband of epileptic woman. There were genetic factors and chromosomal anomalies in 18 of the 25 cases with malformations and diseases including epilepsy (72%). This study showed that the occurrence of congenital malformations even without AEDs, and a high influence of genetic factors on the incidence of congenital malformations and diseases including epilepsy. Thus, the genetic factors should be taken into consideration for the offspring of pregnant epileptic women. Furthermore, considering that the incidence of congenital malformations is low in cases with no genetic factors, we should not fear the influence of medication. We should follow the fundamental rules that to use of monotherapy, proper quantities, and requisite minimum for the medical treatment of epilepsy.