Fetal Hydantoin Syndrome

What is Fetal Hydantoin Syndrome?

When embryo or the unborn fetus expose to phenytoin, an anticonvulsant agent causes anatomical disorders, which is termed as a fetal hydantoin syndrome. This is rare symptom, as most of the time doctors avoid prescribing phenytoin to women in their childbearing age. Fetal hydantoin syndrome is the effect of teratogenic effect of the anticonvulsant drugs like phenytoin. Dilantin is one of the popular brand names of the phenytoin. (1)

Fetal Hydantoin Syndrome

Sign & Symptoms

The symptoms mostly arise as congenital disorders, but sometimes all the symptoms may not be perceptible at the time of birth and the symptoms are not same in every case, it varies with one child to others.

All the below mentioned symptoms may not be present in every case, but in this article, it is tring to jot down all the clinical findings, obtain from different case studies and accumulated by different clinicians in different case related studies. Following are the included symptoms:

Fetal Hydantoin Syndrome Symptoms Signs

Prenatal growth deficiency

Affected newborn has low birth growth and it may range from mild to severity, even after birth , it also affects postnatal growth due to growth deficiency.

Distinctive craniofacial abnormalities

This includes a broad, flat bridge of the nose; nose is short in size; eyes are abnormally spaced out from each other (hypertelorism); alignment of the eyes is not usual (strabismus); drooping upper eyelids (ptosis); mouth size is wider and larger than the normal; deformed ears; mild webbed neck (pterygium colli); and abnormally small head size (microcephaly). Cleft lip (gap in the upper lip) or cleft palate (gap on the upper palate of the mouth) is also common in different case findings.

Facial and body hair growth is much more than the usual.

Cognitive deficiency and delayed motor functioning

Microcephaly does not only affect the cranial size, but also affect the brain development and therefore learning disability and locomotion ability is also hampered and causes developmental delays like delay in crawling or sit up. In many case reports it may recover with age, but a definite statement in regards of neurological development is not yet clear.

Structural deformity in fingers and toes

In some cases, it is noticeable that stiff, narrow shaped or undersized fingers and toes, toes look similar as fingers (digitalized toes) and deformed and small nails in both fingers and toes. In some cases, extra finger is also observed.

Additional not frequently observed in every case history

  • Congenital heart defects
  • Cardiac arrhythmia
  • Attention deficit hyperactivity disorder or other behavioral abnormalities
  • Vision disturbance, which include myopia (nearsightedness)
  • Lack of joint firmness
  • Renal disorders
  • umbilical (affect close to the navel) and inguinal (related to intestine) hernia

Medical report also suggests that the fetal hydantoin syndrome may increase the probability related to the progression of the definite non cancerous or cancerous tissue growth (tumors) like Wilm’s tumor, ectodermal tumors or neuroblastoma, though no scientific research prove this yet.

It has been already disclosed that all the cases of fetal hydantoin syndrome are not having a particular sign or symptoms, therefore it is suggested that parents should discuss in details about the observed sign and symptoms of their infant with an expert health care team, so that proper treatment plan they can arrange to reduce the future complications. (3,4)


Phenytoin ( Dilantin ) is the drug which causes teratogenic effect due to deficiency of vitamin D and vitamin K, which hamper the uterine fetus development. The phenytoin also interfere with the maternal folic acid absorption. Folic acid is a very important component for hematological development of the fetus. Therefore deficiency of all these vitamins all together in the maternal physiology hampers the proper anatomical development of the fetus and resultant wide range of anomalies are engaged with the newborn.

Other than Phenytoin (Dilantin), if any factor affects the folic acid deficiency in the mother’s body, different fetal hydantoin syndrome related symptoms arise in the newly born infants.

Methylenetetrahydrofolate reductase (MTHFR) gene mutation may associated with fetal hydantoin syndrome. This is suspected that metabolism of phenytoin or its metabolites produce intermediate metabolites and they are the main culprit. The free radicals of these intermediate metabolites can attach to proteins, lipids or DNA, and harmfully distresses neurodevelopment. (6)

Complications of Phenytoin to mother

If a nursing mother administered Phenytoin, then the following risk factors are associated

  • Phenytoin can excrete through breast milk, as it effortlessly mixed-up with mother’s milk. Therefore, the child at risk of getting some symptoms related to the fetal hydantoin syndrome.
  • Usually the symptoms are milder for breastfeeding babies in contrast with uterine exposure to phenytoin, as in nursing mother maximum drugs are utilized to maintain the blood plasma level for keep up the therapeutic range and very little amount reached to the breast milk, the ratio is normally 0.54: 0.18.
  • The included symptoms after reaching the phenytoin to the infant through breast milk are sucking capacity becomes decreased and drowsiness, no other ailing effect observed.
  • The American Academy of Pediatrics trusted that the Phenytoin medicine does not cause any side effect to breast milk. (6)


Yet now no traditional diagnostic test is developed for quick identification of the cases, with gradual revealing the symptoms the fetal hydantoin syndrome is highlighted.

  • Depending upon the sign and symptoms corrective therapeutic measures are taken by the team of the expert clinicians. Usually, cleft lip or cleft palate can be rectified by surgical interventions.
  • Other supportive treatment and learning and vocational training is provided for improvement of the quality of life of the patient.
  • Behavioral therapy and boosting of cognitive efficiency can reduce the learning deficiency.
  • Sometimes, parental counseling becomes important for proper parenting of the affected child.


  • The best option to protect your child from the fetal hydantoin syndrome, the following preventive measures should be followed:
  • Do not recommend or take any anticonvulsant medication at the child bearing age.
  • Folic acid supplementation before and after conception to till delivery should be continued in case of compulsion to take anticonvulsant medications for the mother. (2,5,6)


  1. Fetal Hydantoin Syndrome (2015); WebMD Medical Reference from the National Organization for Rare Disorders; Retrieve from: http://www.webmd.com/a-to-z-guides/fetal-hydantoin-syndrome
  2.  Fetal Hydantoin Syndrome (2015); Retrieve from: http://rarediseases.org/rare-diseases/fetal-hydantoin-syndrome/
  3.  Dr Abhilash Sandhyala and Radswiki et al.; Fetal hydantoin syndrome; Retrieve from: http://radiopaedia.org/articles/fetal-hydantoin-syndrome
  4.  Pr Asher ORNOY (2015); Fetal hydantoin syndrome; Retrieve from: http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=1912
  5.  Fetal hydantoin syndrome (2011); Retrieve from: https://rarediseases.info.nih.gov/gard/6435/fetal-hydantoin-syndrome/resources/1
  6.  Prasenjeet Banerjee; Fetal Hydantoin Syndrome; Retrieve from: http://www.hxbenefit.com/fetal-hydantoin-syndrome.html

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