Developmental field defects: coming together of associations and sequences during blastogenesis

We report on two patients with an unusual combination of multiple congenital anomalies including holoprosencephaly, encephalocele, and additional defects commonly observed in the VACTERL and schisis "associations." One of the infants had a chromosome abnormality characterized by partial duplication and deletion of chromosome 18. VACTERL association was characterized recently as a primary developmental field defect (DFD) [Martínez-Frías et al., 1998: Am J Med Genet 76:291-296]. In some cases, sequences may also represent uncomplicated DFDs. We suggest that findings in both of these cases represent abnormalities of blastogenesis involving the primary field resulting in holoprosencephaly and VACTERL and schisis anomalies, and show that similar primary DFDs are causally heterogeneous.