Focal abdominal wall hernias and pre-axial toe polydactyly define distinct phenotypes and etiologies for infants of diabetic mothers and the VATER Association

Three newborn infants of mothers with insulin dependent diabetes mellitus (IDDMm) were found to have multiple congenital malformations consisting of 3 or more VATER ascertainment anomalies. In addition, each of the 3 infants also had left lateral abdominal wall hernias, not previously noted in VATER or IDDMm infants. The hernias had intact overlying skin, were easily reducible and approximately 5-8 cm in diameter. Abdominal wall hernias with intact overlying skin are unusual, especially on the left side. One infant came to autopsy and was found to have hypoplasia (amyoplasia) of the abdominal wall musculature. Each of these 3 infants also had bilateral toe pre-axial polydactyly which has been rarely reported in VATER or in IDDMm infants. While there is overlap in the anomalies of VATER Association and infants of IDDMm, these 3 infants of IDDMm suggest that the phenotypes are distinct with separate etiologies. In VATER, an early insult to the allantois and subsequent vascular consequences have been etiologically implicated. The pre-axial toe potydactyly and abdominal wall hypoplasias are related to mesenchyme. The presence of macrosomia and increase in number of cells with IDDM can result in excess mesenchyme at the time of limb bud development which has been linked to polydactyly. The focal abdominal wall amyoplasia derives from myotomal mesoderm which migrates from 3 directions to fuse in the midline. An excess of mesodermal cells can cause imperfect fusion and migration resulting in a focal defect.