Craniosynostosis Following Fetal Methotrexate Exposure

Area of Science:

• Developmental Biology
• Teratology
• Clinical Genetics

Background:

• Methotrexate (MTX) is a folic acid antagonist used therapeutically but known to be a potent teratogen.
• Methotrexate embryopathy is characterized by multiorgan system dysfunction, including growth restriction and various congenital abnormalities.
• The teratogenic effects of MTX on fetal development are still being elucidated.

Observation:

• This case series describes 4 patients exposed to MTX prenatally.
• All 4 patients presented with craniosynostosis, a condition involving premature closure of cranial sutures.
• This represents the largest published cohort associating prenatal MTX exposure with craniosynostosis.

Findings:

• Prenatal exposure to methotrexate is associated with an increased risk of craniosynostosis.
• Craniosynostosis is a significant manifestation of methotrexate embryopathy.
• This finding expands the spectrum of known congenital abnormalities linked to in utero MTX exposure.

Implications:

• Clinicians should be aware of the potential for craniosynostosis in infants with prenatal MTX exposure.
• Enhanced surveillance for skeletal and craniofacial anomalies may be warranted in exposed pregnancies.
• Further research is needed to understand the mechanisms underlying MTX-induced craniosynostosis.