Yolanda BW.indd

Objective Increased nuchal translucency in the human fetus is associated with aneuploidy, structural malformations and several syndromes such as Noonan syndrome. In 60-70% of the Noonan syndrome cases, a gene mutation can be demonstrated. Previous research showed that aneuploid fetuses with increased nuchal translucency demonstrate an aberrant lymphatic endothelial diff erentiation. Methods Fetuses with increased nuchal translucency and normal karyotype (n = 7) were compared with euploid controls having a normal nuchal translucency (n = 5). A Noonan syndrome gene mutation was found in three out of seven fetuses with increased nuchal translucency. Endothelial diff erentiation was evaluated by immunohistochemistry using lymphatic markers (Prox-1, Podoplanin, LYVE-1) and blood vessel markers VEGF-A, NP-1, Shh, vWF and smooth muscle cell marker SMA. Results Nuchal edema and enlarged jugular lymphatic sacs were observed in fetuses with increased nuchal translucency, together with abnormal lymphatic endothelial diff erentiation i.e. the presence of blood vessel characteristics, including high levels of VEGF-A and NP-1 expression. The enlarged jugular lymphatic sacs contained erythrocytes and were surrounded by smooth muscle cells. Conclusion This study shows an aberrant lymphatic endothelial diff erentiation in fetuses with increased nuchal translucency and a normal karyotype (including Noonan syndrome fetuses), as was previously reported before in aneuploid fetuses. Yolanda BW.indd 74 21-12-10 13:52