Fetal Hydantoin Syndrome

National Organization for Rare Disorders, Inc.

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  • Dilantin Embryopathy
  • Phenytoin Embryopathy

Disorder Subdivisions

  • None

General Discussion

Fetal Hydantoin Syndrome is a rare disorder that is caused by exposure of a fetus to the anticonvulsant drug phenytoin (Dilantin). The symptoms of this disorder may include abnormalities of the skull and facial features, growth deficiencies, underdeveloped nails of the fingers and toes, and/or mild developmental delays. Other findings occasionally associated with this syndrome include cleft lip and palate, having an unusually small head (microcephaly) and brain malformations with more significant developmental delays.


The child with Fetal Hydantoin Syndrome may be small at birth, with increased hair on the body and face, and with poorly developed fingernails and toenails. He or she may have poor muscle tone and may be developmentally delayed.

As the children grow older, the developmental delays improve, but studies suggest that children may remain slightly behind unexposed siblings. The growth delays remain through life, as does the tendency to have increased body hair (hirsutism).

About 3 percent of the infants exposed to Dilantin will have brain malformations, cleft lip and palate, and severe developmental delays.

The most consistent facial features found in affected infants have been a flat bridge of the nose, and eyes that are down-slanted, widely spaced, and crossed (strabismus). An underdeveloped vertical groove in the center of the upper lip (philtrum), cleft lip and/or palate, drooping eyelids (ptosis), and mild webbing of the neck have also been reported.

Growth deficiencies may include underdeveloped fingers and toes, malformed nails as well as finger-like thumbs.


Fetal Hydantoin Syndrome is a rare disorder that is caused by exposure of a fetus to phenytoin (Dilantin) which is an anticonvulsant drug prescribed for epilepsy. Not all infants exposed to phenytoin will be affected with the disorder.

There is a 7 to 10 percent risk that babies born to mothers taking phenytoin (Dilantin) for seizure control or other medical indications during pregnancy will exhibit some or all of the features of Fetal Hydantoin Syndrome.

There have been documented cases in which affected and unaffected siblings have been exposed to the same amount of this drug. Other factors, such as decreased folic acid levels in the mother, may add to the likelihood that the child will exhibit features of the syndrome.

Affected Populations

Worldwide, approximately 2 million women are exposed to phenytoin (Dilantin) during pregnancy. The risk is 7 to 10 percent that a fetus exposed to phenytoin will be born with some or all of the features of the syndrome.

Standard Therapies


It is recommended that women be treated with a single anticonvulsant prior to conception and throughout pregnancy, since it appears that children exposed to multiple anticonvulsants may risk more significant birth defects.

Also, it is important for all women to maintain adequate levels of folic acid in the diet, both before conception and during pregnancy. Smoking and alcohol should be avoided during pregnancy.


When cleft lip and/or palate are present, the coordinated efforts of a team of specialists such as pediatricians, dental specialists, surgeons, speech pathologists, and psychologists may be used to plan the child's treatment and rehabilitation. Cleft lip may be surgically corrected. Generally surgeons repair the lip when the child is still an infant. A second surgery is sometimes necessary for cosmetic purposes when the child is older.

Cleft palate may be repaired by surgery or covered by an artificial device (prosthesis) that closes or blocks the opening. Surgical repair can be carried out in stages or in a single operation, according to the nature and severity of the defect. The first palate surgery is usually scheduled during the toddler period.

Special education and related services will be of benefit to children with learning delays. Other treatment is symptomatic and supportive.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:




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Ward RM. Difficulties in the study of adverse fetal and neonatal effects of drug therapy during pregnancy. Semin Perinatol. 2001;25:191-95.

Godbole KG, Gambhir PS, Deshpande AS, et al. Fetal hydantoin syndrome with rheumatic valvular heart disease. Indian J Pediatr. 1999;66:290-93.

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March of Dimes Birth Defects Foundation

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Cleft Palate Foundation

1504 East Franklin Street

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Chapel Hill, NC 27514-2820


Tel: (919)933-9044

Fax: (919)933-9604

Tel: (800)242-5338

Email: info@cleftline.org

Internet: http://www.cleftline.org

Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

Internet: http://rarediseases.info.nih.gov/GARD/

For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.