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Fetal Hydantoin Syndrome

Synonyms of Fetal Hydantoin Syndrome

  • Dilantin Embryopathy
  • Phenytoin Embryopathy

Disorder Subdivisions

  • No subdivisions found.

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.

Related Disorders

Symptoms of the following disorders can be similar to those of Fetal Hydantoin Syndrome. Comparisons may be useful for a differential diagnosis:

Aarskog Syndrome is thought to be inherited as a a sex-linked dominant trait. Males with Fetal Hydantoin Syndrome may have symptoms similar to those of Aarskog Syndrome. Infants affected with Aarskog Syndrome may have widely spaced eyes (hypertelorism) with drooping eyelids (ptosis), and a short broad nasal bridge. Short broad fingers and toes as well as stunted growth, genital abnormalities and mild mental retardation may also be present. (For more information on this disorder, choose "Aarskog Syndrome" as your search term in the Rare Disease Database.)

Noonan Syndrome is a rare disorder that may be inherited as an autosomal dominant or autosomal recessive genetic trait. Symptoms of this disorder may also be similar to those of infants affected with Fetal Hydantoin Syndrome. This disorder is mainly characterized by a lack of sexual development, short stature, possible mental retardation, a webbed neck, widely spaced eyes with drooping eyelids, and/or skeletal abnormalities. (For more information on this disorder, choose "Noonan Syndrome" as your search term in the Rare Disease Database.)

Fetal Alcohol syndrome (FAS) is a syndrome of altered fetal growth resulting in certain birth defects due to maternal consumption of alcohol during pregnancy. When a pregnant woman drinks alcoholic beverages, a pattern of defects in the fetus may occur, depending on the age of the fetus at the time. In many cases, affected infants are unusually small at birth, have an abnormally small head (microcephaly), and may fail to gain weight and grow at the expected rate (failure to thrive). Affected infants and children may exhibit delays in intellectual development, as well as in the acquisition of fine and gross motor skills. (For more information on this disorder, choose "Fetal Alcohol Syndrome" as your search term in the Rare Disease Database.)

Phenobarbital and carbamazepine have also been reported to produce findings similar to those associated with exposure of the fetus to phenytoin. Nonetheless, because complications can result from frequent seizures during pregnancy, pregnant women with epilepsy should be given phenytoin, carbamazepine, or phenobarbital in the smallest effective dose and should be closely monitored.

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

Fetal Hydantoin Syndrome Resources

NORD Member Organizations:

(To become a member of NORD, an organization must meet established criteria and be approved by the NORD Board of Directors. If you're interested in becoming a member, please contact Susan Olivo, Membership Manager, at solivo@rarediseases.org.)

Other Organizations:

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.

The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.

Report last updated: 2008/04/25 00:00:00 GMT+0

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