OC05.02: Increased nuchal translucency origins from abnormal lymphatic development and develops regardless of the presence of a congenital heart defect

Impaired cardiac function and abnormal lymphatic development are the two main theories to explain increased nuchal translucency (NT). Increased NT is strongly associated with congenital heart defects and the risk of a cardiac abnormality augments with increasing NT. The causal relation between increased NT and congenital cardiac anomalies, however, remains unexplained. A morphological examination of increased NT, lymphatic development and cardiac defects combined, however, is lacking. Our aim is to examine to what extent abnormal lymphatic and cardiovascular development are mutual characteristics in various mutant mouse models with and without nuchal edema (the morphological equivalent of increased NT). Mouse embryos with cardiac anomalies and nuchal edema (Fkbp12-/-, Tbx1-/-, Chd7-/-, Jarid2-/-), cardiac malformations without nuchal edema (Pitx2-/-, Tbx2-/-) and mouse embryos without cardiac defects but with lymphatic developmental abnormalities with nuchal edema (Ccbe1-/-) and without nuchal edema (Ccbe1+/-) were examined. Embryos were analyzed from embryonic day 12.5–15.5. Markers for blood vessels, lymphatic vessels and nerves were used to study the nuchal region and the lymphatic system. Hematoxylin and Azophloxine staining was performed to examine the cardiovascular morphology. In embryos with complex cardiac abnormalities and nuchal edema (Fkbp12-/-, Tbx1-/-, Chd7-/-, Jarid2-/-) enlarged jugular lymph sacs (JLS) were found. Embryos with normal cardiac morphology and nuchal edema (Ccbe1-/-) showed no formation of the JLS. In embryos with a complex cardiac defect without nuchal edema (Pitx2-/- and Tbx2-/-) a normal size of the JLS was observed. Embryos with normal cardiac morphology without nuchal edema (Ccbe1+/-) revealed a normal size of the JLS. This study shows that abnormal lymphatic development causes nuchal edema. Nuchal edema develops regardless of the presence of a congenital heart defect.