Occurrence of Neural Tube Defects at Multiple Separate Sites

Résumé

ABSTRACT Background Single neural tube defects (NTDs) are among the most serious and common birth defects of the nervous system with a prevalence of ~5 per 10,000 births in countries with dietary folic acid fortification. The occurrence in the same individual of multiple NTDs—two or more such anomalies in the cerebrospinal axis separated by segments of normally closed neural tube—occurs much less frequently. Methods We studied phenotypic and epidemiological characteristics in 21 MNTD cases from three centers, and in 128 similar cases from the literature. Results MNTDs differ from single NTDs in many respects. Anencephaly, open meningomyeloceles and large encephaloceles are rarer, while small cephaloceles and various forms of spinal dysraphism (e.g., split cord malformations, lipomas) are often seen. Common patterns are a cranial defect with a spinal anomaly and pairs of spinal defects. While some cases were identified during pregnancy or in the neonatal period, many others only came to attention a week or more after birth. There were fewer associated anomalies and surviving children tended to have less motor and cognitive dysfunction. Conclusions Although defects of primary neurulation can be seen in MTNDs, failures in pre‐neurulation and post‐neurulation processes are frequent contributors to the specific locations and types of multisite neural tube defects observed. Abnormal secondary neurulation appears rare. To date, there are few clues as to what genetic and/or environmental risk factors might lead to these unusual patterns of neural tube dysmorphogenesis.