To investigate the prenatal diagnosis and genetic counseling of fetal nuchal fold (NF) thickening.

This study retrospectively analyzed 17 fetuses with increased NF detected by prenatal ultrasound examination in Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences from December 1, 2016 to December 1, 2017. All cases were divided into isolated (isolated group) or non-isolated increased NF group (non-isolated group) according to whether the fetus had concomitant ultrasonographic abnormalities or not. Karyotype and chromosomal microarray analysis (CMA) were performed on all cases. Clinical data, prenatal genetic testing results and pregnancy outcomes were analyzed.

Of those twelve cases in the isolated group, two were terminated due to the identification of chromosomal abnormalities and pathogenic copy number variations (CNVs) and the fetal autopsy results were consistent with the prenatal diagnosis. The rest 10 pregnancies were all continued including one fetus carrying a variant of unknown significance, which was proved to be a paternal heredity by CMA, and nine without genetic abnormalities and all-these infants were healthy during follow-up. Among the five non-isolated cases, one was diagnosed as trisomy 21 by karyotyping and CMA, and the other four were found to have structural abnormalities under ultrasound scan, but without genetic abnormalities in karyotyping and CMA. And all the five pregnancies were terminated after genetic counseling and three of them chose whole exome sequencing (WES) for further test. One homozygous mutation in CHRNA1 gene and one de novo mutation in SETD2 gene were found in two cases, respectively, while no abnormality was identified in the other one case.

Once increased NF were indicated by ultrasound examination, prenatal genetic testing should be offered to the patients, including CMA, regardless of other ultrasonographic abnormalities, and WES should also be offered when necessary. Considering a thickened NF is associated with increased risks of structural defects, a close follow-up with fetal echocardiography and ultrasound is required even the prenatal tests are normal.

Nuchal translucency measurement; Ultrasonography, prenatal; Chromosome aberrations