Pathophysiology of increased nuchal translucency in chromosomally abnormal fetuses

Abstract

Objective: In about 80% of fetuses with trisomies, 21, 18 or 13 and Turner syndrome there is increased collection of fluid in the neck region that can be visualized sonographically at 10-14 weeks of gestation as increased nuchal translucency thickness. The pathophysiology of this common phenotypic expression of different chromosomal abnormalities is uncertain but there is some evidence that the underlying mechanism may be cardiac failure, possibly due to abnormalities of the heart and great arteries, and altered composition of the skin. The latter may be due to a gene dosage effect of the three, rather than the normal two copies of genes, found in trisomies causing an alteration of the extracellular matrix in the skin or abnormal development of the heart and great arteries.

Full Text

Methods: We performed a number of studies investigating nuchal skin tissue for extracellular matrix components and lymphatic hypoplasia. We also performed studies investigating cardiac heart failure using molecular techniques and doppler studies by measuring the ductus venosus at 12-14 weeks of gestation. Big vessels were analyzed using light microscopy.

Results: Studies investigating the heart found increased mRNA gene expression of ANP and BNP and reduced mRNA gene expression of Calcium ATPase. Doppler studies of the ductus venosus in chromosomally abnormal fetuses found signs of heart failure like a negative А-wave in chromosomally abnormal fetuses. Studies of great arteries in chromosomally abnormal fetuses found narrowing of the aortic isthmus. Studies investigating components of the extracellular matrix in nuchal skin of trisomic fetuses found overexpression of ECM genes in trisomies or an altered ratio of genes and lymphatic hypoplasia in Turner.

Conclusions: The present data provide some evidence, that chromosomally abnormal fetuses with increased nuchal translucency at 12-14 wks may suffer from transient cardiac heart failure due to narrowing of the aortic isthmus or an altered extracellular matrix of the heart and skin. This could be transient because an increase in the radius of the big vessels leads to a decrease in the vascular resistance by ten to the minus four (equation of Hagen-Poisseuille).