Fetal hydantoin syndrome

The fetal hydantoin syndrome is a variable pattern of altered growth (pre and postnatal), mental deficiency, unusual facies, distal phalangeal hypoplasia, and other defects occurring in some infants exposed in utero to hydantoins. This altered pattern of morphogenesis is distinct from other recognized disorders. It has been reported only in the offspring of women using hydantoins. One case is presented and several aspects of the diagnosis are discussed.

Diphenylhydantoin (phenytoin) is a widely used drug with multiple adverse effects, several of them cutaneous. Prenatal exposure to hydantoins may result in a spectrum of structural, developmental, and behavioral changes known as the fetal hydantoin syndrome (FHS). A patient with the dysmorphic characteristics of FHS had unusual hyperpigmentation of several fingernails, a finding which has not been described in other patients with FHS. We propose a mechanism for the dysmorphic action of phenytoin on the developing fetus, consonant with the known effects of hydantoins on collagen metabolism...

We present the clinical picture of a patient with the fetal hydantoin syndrome. A review was made on etiology, pathogenesis, in this syndrome and the recommended medical management for the epileptic mother during pregnancy.

The A/J mouse has been used to study the teratogenic affects of phenytoin. The developmental abnormalities produced in offspring of this model are similar to some of the malformations observed in cases of human "fetal hydantoin syndrome." Placing pregnant A/J mice in a hyperoxic chamber after phenytoin injection greatly reduces the incidence of phenytoin-induced cleft lip and palate. These results suggest that phenytoin may affect embryonic development indirectly by altering maternal physiology. This maternally mediated mechanism, and the protection against it afforded by hyperoxia, has general implications for the effects of maternal toxicity on teratogenesis...

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An animal model system has been established which reproduces some of the features of the Fetal Hydantoin Syndrome. This pattern of altered growth and development includes growth retardation, craniofacial anomalies, distal phalangeal hypoplasia, and mental deficiency. Rats exposed in utero to phenytoin on gestational days 9, 11, and 13 exhibited fetal onset growth retardation, abnormalities of the craniofacial region and axial skeleton. In addition, the exposed offspring had significantly lower fetal weights, a shortened snout and a high-arched, irregular palate, and significant delays in skeletal maturation...

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All neoplasms observed in association with the fetal alcohol and hydantoin syndromes are reviewed. Combined teratogenesis and presumed fetal oncogenesis are discussed in addition to the known adult oncogenic potential of alcohol and hydantoin. Both the types of neoplasms and the organ systems affected are different in adults exposed to alcohol and hydantoin than in children exposed to the same presumed oncogens prenatally. Thus, dissimilar biologic processes are implicated, the presumed fetal oncogenic effects differing from the adult oncogenic effects...

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To test the effect of maternal seizure disorders on prenatal structural development, the mouse neurological mutant quaking (qk) was used. Administering phenytoin in the drinking water of females homozygous for the quaking allele reduced the frequency of tonic-clonic seizures typical for this mutant from a background rate of 2.06 to 0.34 seizures per mouse day. As the seizure frequency decreased, the percentage of fetuses exhibiting abnormalities associated with the mouse fetal hydantoin syndrome increased from 0 to 77...

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Anticonvulsant therapy during pregnancy with the hydantoin phenytoin carries a risk of teratologic sequelae and developmental retardation known as the fetal hydantoin syndrome. The putative teratogen is a highly reactive arene oxide intermediate produced during phenytoin metabolism. By using two structurally similar hydantoins, mephenytoin and its in vivo demethylated metabolite nirvanol, we examined the possibility for a stereoselective dissociation of fetal hydantoin toxicity from maternal anticonvulsant activity...

The neuroactive drugs taken by pregnant women have two principals side effects: a teratogenic effects and a postnatal withdrawal effect. Three are the characteristic syndromes: the hydantoin-barbiturate syndrome, the trimethadione-paramethadione syndrome, the fetal alcohol syndrome. The prenatal exposure to heroine and to morphine interfere mainly with the cerebral development. Drug addiction, like postnatale withdrawal syndrome, are mainly due to passive exposure to drug narcotic (heroine, methadone), to sedative-hypnotic agents (barbiturates Diazepam Chlordiazepoxide) and to alcohol...

Children of epileptic mothers have a higher risk for major malformations. A similar increase of major malformations is observed in children of epileptic fathers suggesting that the major malformations are related to the parental disease rather than to the antiepileptic drug. No information was available if the pattern of minor acrofacial malformations known as the "hydantoin syndrome" occurs also in children of epileptic fathers. We studied 37 children of treated mothers and 22 children of treated fathers with epilepsy...

This paper presents the case report of a 2 year-old boy in whom a grade II fetal alcohol syndrome was diagnosed at 17 months. At 21 months, an embryonal rhabdomyosarcoma of the urinary bladder trigone was found, and the tumour excised. Polychemotherapy was initiated, but bone-marrow depression and death in septicaemic shock followed. The main autopsy findings included the demonstration of tumour remnants in the urinary bladder and prostate, and a severe acute purulent pyelonephritis. This is the fifth case of fetal alcohol syndrome in conjunction with a malignant tumour to be reported in the international literature...

The long-term behavioral outcome subsequent to prenatal exposure to phenytoin was examined in an animal model for the Fetal Hydantoin Syndrome. Behavioral outcome was determined by two different techniques--the residential maze, which provided a 24-hour measure of horizontal movement frequency in a group of animals, and time-lapse photography, which allowed quantification of frequency, duration, distribution, and sequencing of 15 motor acts performed by individual rats. Phenytoin induced significant, sex-related changes in motor behavior...

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