Correspondence

Prenatal Prediction of Risk of the Fetal Hydantoin Syndrome

N Engl J Med 1993; 329:1660-1661November 25, 1993

Article

To the Editor:

After the publication of our paper “Prenatal Prediction of Risk of the Fetal Hydantoin Syndrome” (May 31, 1990, issue),1 our laboratory received many requests to assay epoxide hydrolase activity in samples of chorionic villi. Our prior work had established standards for measuring this enzyme in amniocytes and skin fibroblasts and used those standards to assist in predicting the risk of the fetal hydantoin syndrome. In an effort to determine whether measurement of epoxide activity in chorionic-villus samples could be used in a similar manner, we cultured 50 samples randomly obtained from pregnant women who were requesting fetal karyotyping because of their advanced age (none were taking phenytoin [Dilantin] or any other anticonvulsant). The samples were analyzed according to the technique described in our paper1 and were compared with amniocyte controls from the previous study that were considered to have activity of 100 percent. In each experiment, controls were run simultaneously, and enzyme activity in the chorionic-villus samples was expressed as a percentage of control levels. The mean level of activity in the 50 samples was 36.7 percent (95 percent confidence interval, 32.7 to 40.6). The standard deviation was 13.9 percent, whereas sample variation was 2 percent on separate analyses of the same cells. The previously determined mean level of activity in 100 amniocyte samples was 51.7 ±2.5 percent of control. To determine whether direct rather than cultured preparations of chorionic villi would be more comparable, we tested four direct preparations and found enzyme levels lower than those in cultured samples.

On the basis of previous testing of patients known to have the fetal hydantoin syndrome, epoxide hydrolase activity of less than 30 percent of control was considered to indicate an increased risk of the syndrome; subsequent testing has suggested that mildly affected patients may have levels in the range of 35 percent of control. On this basis, the mean level of activity in our chorionic-villus samples would fall just outside the range in affected persons; this lowered level of activity appears to preclude the use of this type of cell for prenatal prediction of the syndrome. The exact mechanism responsible for the lower levels of epoxide hydrolase activity in chorionic villi is not understood, since it does not appear to be a function of the growth, confluence, or viability of the cells.

Therefore, we are not recommending chorionic-villus sampling for prenatal prediction of susceptibility to hydantoin-associated teratogenesis. Similarly, we would not recommend the use of placental cultures to assist in diagnosing the fetal hydantoin syndrome after delivery.

Bruce A. Buehler, M.D.
University of Nebraska Medical Center, Omaha, NE 68198

David Bick, M.D.
Genetics and IVF Institute, Fairfax, VA 22031

Duane Delimont, M.S.
University of Nebraska Medical Center, Omaha, NE 68198

1 References

1. 1

   Buehler BA, Delimont D, van Waes M, Finnell RH. Prenatal prediction of risk of the fetal hydantoin syndrome. N Engl J Med 1990;322:1567-1572
   Full Text | Web of Science | Medline

Citing Articles (4)

Citing Articles

1. 1

   G Schaefer, Bruce Buehler. 2011. Life Care Planning for Children with Genetic Disorders. , 679-696.
   CrossRef

2. 2

   Dalia Kasperavičiūtė, Sanjay M Sisodiya. (2009) Epilepsy pharmacogenetics. Pharmacogenomics 10:5, 817-836
   CrossRef

3. 3

   Rajan Khetarpal, Ghanshyam Halwai, R. K. Marwaha, Amita Trehan, K. L. Narasimhan, A. K. Bhalla. (1999) Retro-peritoneal cystic lymphangioma in association with fetal hydantoin syndrome. The Indian Journal of Pediatrics 66:2, 294-297
   CrossRef

4. 4

   Gerald V. Raymond, Bruce A. Buehler, Richard H. Finnell, Lewis B. Holmes. (1995) Anticonvulsant teratogenesis: 3. possible metabolic basis. Teratology 51:2, 55-56
   CrossRef