Aberrant lymphatic development in euploid fetuses with increased nuchal translucency including Noonan syndrome.
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 (NT) demonstrate an aberrant lymphatic endothelial differentiation.


METHODS
Fetuses with increased NT and normal karyotype (n = 7) were compared with euploid controls having normal NT (n = 5). A Noonan syndrome gene mutation was found in three out of seven fetuses with increased NT. Endothelial differentiation was evaluated by immunohistochemistry using lymphatic markers (PROX-1, Podoplanin, LYVE-1) and blood vessel markers vascular endothelial growth factor-A (VEGF-A), Neuropilin-1 (NP-1), Sonic hedgehog, von Willebrand factor, and the smooth muscle cell marker, smooth muscle actin.


RESULTS
Nuchal edema and enlarged jugular lymphatic sacs (JLSs) were observed in fetuses with increased NT, together with abnormal lymphatic endothelial differentiation i.e. the presence of blood vessel characteristics, including high levels of VEGF-A and NP-1 expression. The enlarged JLSs contained erythrocytes and were surrounded by smooth muscle cells.


CONCLUSIONS
This study shows an aberrant lymphatic endothelial differentiation in fetuses with increased NT and a normal karyotype (including Noonan syndrome fetuses), as was previously reported before in aneuploid fetuses.
Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands.
Yolanda M
YM
de Mooij
Nynke M S
NM
van den Akker
Mireille N
MN
Bekker
Margot M
MM
Bartelings
John M G
JM
van Vugt
Adriana C
AC
Gittenberger-de Groot
D004729:Endothelium, Lymphatic / Q000002:abnormalities / Q000000981:diagnostic imaging; D005260:Female; D047109:Fetal Development; D006801:Humans; D007621:Karyotyping; D008206:Lymphatic Diseases / Q000151:congenital / Q000000981:diagnostic imaging; D008208:Lymphatic System / Q000002:abnormalities*; D009634:Noonan Syndrome / Q000150:complications / Q000000981:diagnostic imaging*; D048208:Nuchal Translucency Measurement; D011247:Pregnancy; D016216:Ultrasonography, Prenatal