Role of collagen type IV in the pathogenesis of increased prenasal thickness in Down syndrome fetuses: Sonographic and immunohistological findings

The present study aims to compare the presence and localization of collagen type IV in the prenasal tissue of fetuses with and without Down syndrome (DS). Products of conception were obtained from mid-gestation uterine evacuations of 14 DS fetuses and 15 unaffected controls. Microdissection of the prenasal area and an analysis of the prenasal tissue specimens were performed by a single pathologist, blinded to the karyotype results. Immunohistological presence and localization of type IV collagen were analyzed in the basement membrane (BM), blood vessels, and stroma of the tissues. There were no statistically significant differences in the presence and localization of antibodies for collagen IV in the blood vessels and stroma between the two groups. However, the presence and localization of type IV collagen in the BM of the prenasal skin were significantly higher in DS specimens compared to the control group (P=0.023). When combining both groups altogether, a significant correlation was found between the increased prenasal thickness (PT) and the high presence and location of collagen type IV, irrespective of the karyotype results (Spearman's correlation; R=0.459; P=0.012). Using the immunohistochemistry technique, we were able to confirm the overexpression of collagen type IV in the BM of the prenasal area. This may explain the sonographic finding of increased PT seen mainly in DS fetuses.