Fetal Hydantoin Syndrome

What is Fetal Hydantoin Syndrome?

In exposure to phenytoin drug, the fetus gets abnormally affected due to its teratogenic effect. Phenytoin is an anti-epileptic medication. However, the fatal outcome is not affected every infant exposed to the Phenytoin. [1] Alternatively Fetal Hydantoin Syndrome known as Dilantin Embryopathy, Phenytoin Embryopathy. [2]

Fetal Hydantoin syndrome

The fetal hydantoin syndrome has a wide variety of symptoms and the severity of the symptoms also varied individually to the individual. It has been observed that women using antiepileptic drugs during their pregnancy have a greater risk of fetal hydantoin syndrome for a newborn. The incidence rate showed almost 10 to 30 percent of pregnant women deliver neonates with fetal hydantoin syndrome as they expose to Phenytoin during their pregnancy.

Signs and Symptoms

It is not necessary that all below mentioned sign and symptoms are noticeable to all affected infants. Usually, only a few infants have all the following symptoms.

  • The symptoms of fetal hydantoin syndrome are associated with skull and facial abnormalities, growth retardation, undersized fingers, toes and nails and mildly delayed development.
  • Both prenatal and post-natal development is retarded
  • At the time of birth low weight with small sized neonates with poorly developed nails and increased facial and scalp hair growth are mostly observed in infants who exposed to phenytoin during their fetal stage.
  • Decreased muscular tone may observe in infants who exposed to phenytoin during their fetal stage.
  • The abnormal facial features include a flat nasal bridge, short nose, philtrum or an erect, undeveloped groove at the middle of the upper lip, a wide mouth; cleft lips or oral clefts; and low seated malformed ears. The size of the nose is short.
  • The neck size is also decrease
  • Microcephaly or abnormally small head sized often cause malformation of internal brain structure and cause delayed mental development along with impaired neurological findings are more than two three times common.
  • The fingers arrangement is also abnormal, as they arranged in widely distant fashion and finger like the thumb is also characteristic feature.
  • Some less common abnormalities include eye defects, like down-slanted eyes; hypertelorism means widely spaced eyes; strabismus or crossed eyes; ptosis or drooping eyelids; and/or folded eye covering skin at the inner corner of the eye, which is also termed as epicanthal folds.
  • Infants with fetal hydantoin syndrome have a higher risk of cardiac disorder, umbilical and inguinal hernias and hypospadias.3

Some of the children also have an increased risk for benign or malignant tumors; the included tumors are Wilms tumor develops in kidney, neuroblastoma in the brain, ectodermal tumors in skin or ependymoma4.

Fetal Hydantoin syndrome Pneumonic


The anti-epileptic drugs are prescribed to mother due to controlling the seizure attack.

But most anti-epileptic drugs, such as phenytoin has a teratogenic effect, means these drugs can cross placental barrier of the pregnant women and reach to the fetus or embryo and provide multiple harmful effects like fetal hydantoin syndrome. Along with phenytoin, most of the time adjunct therapy is also provide to the epileptic mother for better control and that also may influence developmental disorder of the fetus or embryo. Apart from this, specific genetic and environmental factors also influence the fetal hydantoin syndrome.

The exact culprit for the onset of fetal hydantoin syndrome is not yet understood, it is expected that may phenytoin itself or metabolites of phenytoin cause this harmful effect. However, the role of a genetic abnormality or other additional environmental factors like smoking may affect phenytoin metabolism, which is also unclear.

Clinical study report expected that methylenetetrahydrofolate reductase (MTHFR) genetic abnormality in women has a potential risk factor for the onset of fetal hydantoin syndrome. It is assumed that protein material in MTHFR is responsible for proper phenytoin metabolism.

Another scientific approach for progression of fetal hydantoin syndrome is due to abnormal genetic difference causes generation of free radicals from intermediate metabolites of phenytoin causes teratogenesis, as it binds to DNA, proteins, and lipids and that adversely affects neurodevelopment. However, further precise scientific research requires a clear understanding of fetal hydantoin syndrome4.


There is no specific diagnostic test available for detection of fetal hydantoin syndrome. The diagnosis is based on clinical symptoms analysis and analysis of patient case history, which discloses the exposure of phenytoin during gestation. However, it is not necessary that every woman who exposed to phenytoin treatment during gestation have not provided fetal hydantoin syndrome4.


The treatment of fetal hydantoin syndrome is symptomatic, which varies from patient to patient. Usually, a team of experts and healthcare professional work together to provide symptom-specific treatment and also lessen the related complications. To chalk out the treatment plan pediatricians, neurologists, plastic surgeons, oral surgeons, psychologists, and other healthcare professionals need to work together for systematic and comprehensive treatment.

Early detection and appropriate treatment plan can potentially prevent wide abnormality. Surgical intervention can correct cleft lip and/or cleft palate. Along with sophisticated medical treatment, physical, occupational and speech therapy also provide a beneficial effect to the affected children. Additional medical, social and vocational services may also require the management of children affected with fetal hydantoin syndrome. Psychosocial support and counseling for the entire family are also essential to manage the stress level4.


It has been recommended that epileptic women should treat with a single anticonvulsant prior to conception and that should continue throughout the gestation period so that the risk of significant birth defects due to multi-drug exposure can be reduced.

It is also suggested that phenytoin therapy opting women should take folic acid supplements prior to conception and that should continue throughout the gestation period to reduce the risk of neurological malformations.

Education, awareness, and consultation require about the seizure preventive measures and also need to discuss the teratogenic effect of anti-epileptic drugs with expectant mother and family to reduce the risk of fetal developmental problems4.


  1. Fetal hydantoin syndrome; Genetic and Rare Disease Information Center; Retrieve from https://rarediseases.info.nih.gov/diseases/6435/fetal-hydantoin-syndrome
  2. Fetal hydantoin syndrome; WebMed; Retrieve from http://www.webmd.com/a-to-z-guides/fetal-hydantoin-syndrome
  3. Fetal hydantoin syndrome; orphanet; Retrieve from http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=1912
  4. Fetal hydantoin syndrome; National Organization for Rare Disease; Retrieve from https://rarediseases.org/rare-diseases/fetal-hydantoin-syndrome/

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