Fetal Hydantoin Syndrome
Fetal Hydantoin Syndrome (FHS) is a teratogenic disorder characterized by craniofacial anomalies, growth deficiencies, limb abnormalities, and neurodevelopmental impairment resulting from prenatal exposure to the anticonvulsant drug phenytoin (Dilantin) during pregnancy.
Clinical Features
FHS presents with a constellation of abnormalities including:
Craniofacial Features
- Dysmorphic facial features
- Broad nasal bridge
- Low-set or abnormal ears
- Cleft lip and/or palate
- Microcephaly
- Hypertelorism (widely spaced eyes)
Growth Abnormalities
- Prenatal and postnatal growth deficiencies
- Intrauterine growth restriction
- Short stature
Limb and Digital Anomalies
- Hypoplastic nails of fingers and toes
- Distal phalangeal hypoplasia
- Finger-like thumbs
- Altered palmar creases
Neurodevelopmental Issues
- Mild to moderate intellectual disability
- Developmental delays
- Behavioral problems
Other Associated Anomalies
- Cardiovascular defects (including atrial septal defects)
- Ocular defects
- Hypospadias
- Umbilical and inguinal hernias
- Spina bifida and other neural tube defects
Etiology and Risk Factors
FHS is caused by maternal ingestion of phenytoin (Dilantin) during pregnancy. The FDA label for phenytoin clearly states that prenatal exposure may increase risks for congenital malformations and adverse developmental outcomes 1. The syndrome appears to have variable expressivity, with genetic background potentially influencing susceptibility to the teratogenic effects of phenytoin 2.
Diagnosis
FHS is diagnosed based on:
- History of maternal phenytoin use during pregnancy
- Characteristic physical features
- Exclusion of other genetic and teratogenic conditions
FHS is listed as one of the genetic and teratogenic conditions to be considered in differential diagnosis of congenital anomalies 3. The diagnosis requires careful differentiation from other syndromes with overlapping features.
Management
Management of FHS is multidisciplinary and focuses on addressing specific abnormalities:
- Craniofacial anomalies: Surgical correction may be required for cleft lip/palate
- Growth deficiencies: Regular growth monitoring and nutritional support
- Limb abnormalities: Orthopedic evaluation and interventions as needed
- Neurodevelopmental issues: Early intervention services, special education support
- Associated anomalies: Specialty referrals (cardiology, ophthalmology, etc.) based on specific manifestations
Prevention
The most effective prevention strategy is avoiding phenytoin during pregnancy when possible:
- Women with epilepsy who are planning pregnancy should consult with their neurologist about alternative anticonvulsant medications with lower teratogenic risk
- If phenytoin must be used during pregnancy, the lowest effective dose should be employed
- Prenatal screening and monitoring should be intensified for women taking phenytoin during pregnancy
Prognosis
The prognosis varies depending on the severity of manifestations:
- Physical anomalies may require surgical correction but often have good outcomes
- Intellectual disability and developmental delays represent the most concerning long-term consequences 4
- Some children with milder manifestations may have normal intellectual development
Clinical Considerations for Healthcare Providers
- Recognize FHS as a potential diagnosis in children with characteristic features whose mothers took phenytoin during pregnancy
- Be aware that FHS can present with variable severity even among siblings with the same exposure 2
- Consider anesthetic implications in patients with FHS undergoing surgery, as they may have associated cardiac anomalies, spina bifida, or other conditions requiring special anesthetic management 5
- Provide appropriate genetic counseling to mothers who took phenytoin during pregnancy regarding risks in future pregnancies
FHS represents an important reminder of the potential teratogenic effects of anticonvulsant medications and highlights the importance of careful medication selection and monitoring during pregnancy.