Fetal Hydantoin Syndrome

Fetal Hydantoin Syndrome

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Fetal Hydantoin Syndrome is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • 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.

Symptoms

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.

Causes

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

Prevention

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.



Treatment

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:

www.centerwatch.com

References

TEXTBOOK

Menkes JH, au., Pine JW, et al., eds. Textbook of Child Neurology, 5th ed. Baltimore, MD: Williams & Wilkins; 1995:766-67.



REVIEW ARTICLES

Wu SP, Shyu MK, Liou HH, Gau CS, Lin CJ. Interaction between anticonvulsants and human placental carnitine transporter.

Epilepsia. 2004 Mar; 45 (3):204-10.



Scheinfeld N. Phenytoin in cutaneous medicine: its uses, mechanisms and side effects.

Dermatol Online J. 2003 Aug; 9 (3): 6



De Smet L, Debeer P.

Fetal hydantoin syndrome with unilateral atypical cleft hand: additional evidence for vascular disruption. Genet Couns. 2002;13 (2):157-61.



Graeter LJ, Mortensen ME. Kids are different: developmental variability in toxicology. Toxicology. 1996;111:15-20.



Murray JC, Hill RM, Hegemeir S, et al. Lymphoblastic lymphoma following prenatal exposure to phenytoin. J Pediatr Hematol Oncol. 1996;18:241-43.



Sabry MA, Farga TI. Hand anomalies in fetal-hydantoin syndrome: from nail/phalangeal hypoplasia to unilateral acheiria. Am J Med Genet. 1996;62:410-12.



Buehler BA, Rao V, Finnell RH. Biochemical and molecular teratology of fetal hydantoin syndrome. Neurol Clin. 1994;12:741-48.



JOURNAL ARTICLES

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.



Gelineau-van Waes J, Bennett GD, Finnell RH. Phenytoin-induced alterations in craniofacial gene expression. Teratology. 1999;59:23-34.

Resources

March of Dimes Birth Defects Foundation

1275 Mamaroneck Avenue

White Plains, NY 10605

Tel: (914)997-4488

Fax: (914)997-4763

Tel: (888)663-4637

Email: Askus@marchofdimes.com

Internet: http://www.marchofdimes.com



The Arc

1825 K Street NW, Suite 1200

Washington, DC 20006

Tel: (202)534-3700

Fax: (202)534-3731

Tel: (800)433-5255

TDD: (817)277-0553

Email: info@thearc.org

Internet: http://www.thearc.org



Cleft Palate Foundation

1504 East Franklin Street

Suite 102

Chapel Hill, NC 27514-2820

USA

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.

This information does not replace the advice of a doctor. Healthwise, Incorporated disclaims any warranty or liability for your use of this information. Your use of this information means that you agree to the Terms of Use . How this information was developed to help you make better health decisions.

Healthwise, Healthwise for every health decision, and the Healthwise logo are trademarks of Healthwise, Incorporated.