The fetal trimethadione syndrome

Area of Science:

• Teratology and Developmental Pediatrics
• Clinical Genetics and Dysmorphology

Background:

• Maternal exposure to certain medications during gestation is a known risk factor for congenital anomalies.
• Trimethadione, an anticonvulsant, has been previously associated with adverse pregnancy outcomes.
• Understanding the specific teratogenic effects of trimethadione is crucial for prenatal counseling and management.

Purpose of the Study:

• To delineate the specific phenotype associated with in utero exposure to trimethadione.
• To identify key features of fetal trimethadione syndrome through familial and comparative analysis.
• To provide a comprehensive description of anomalies observed in affected individuals.

Main Methods:

• Case series analysis of three families with maternal trimethadione exposure during pregnancy.
• Comparative assessment of siblings within affected families.
• Evaluation of individuals with documented in utero trimethadione exposure.

Main Results:

• A distinct phenotype, fetal trimethadione syndrome, was identified.
• Consistent features include developmental delay, speech difficulty, V-shaped eyebrows, epicanthus, low-set ears with anteriorly folded helix, palatal anomaly, and irregular teeth.
• Additional anomalies observed in some patients: intrauterine growth retardation, short stature, microcephaly, cardiac defects, ocular anomalies, hypospadias, inguinal hernia, and simian creases.

Conclusions:

• In utero exposure to trimethadione results in a recognizable pattern of congenital anomalies, termed fetal trimethadione syndrome.
• The syndrome encompasses a spectrum of developmental, facial, and physical abnormalities.
• Awareness of this syndrome is important for clinicians managing pregnancies exposed to trimethadione.