Genetic examination for fetuses with increased nuchal translucency by exome sequencing

Aim This retrospective study aimed to investigate the value of exome sequencing (ES) in fetuses with isolated first-trimester increased nuchal translucency (NT) and normal chromosomes. Methods ES was performed on 103 fetuses with isolated first trimester increased NT and normal chromosomes. The detection rate of monogenic conditions was analyzed. Results Diagnostic variants were detected in nine cases in which phenotypes and genotypes correlated well, two positive cases were Thanatophoric dysplasia type I, and one case was Kabuki syndrome, which had been detected in previous studies. Eight of the nine cases with diagnostic variants developed additional structural malformations later in pregnancy. Among the nine positive cases, six had a NT thickness between 95th percentile (95th-3.4 mm), and three cases with an increased NT of 3.5 mm or greater. Also, there was no statistical difference in the diagnosis of diagnostic variants in cases with or without a thickened nuchal fold (NF). Conclusions The diagnostic yield of prenatal ES is low for fetuses with an isolated increased NT. In addition to Noonan syndrome, there are additional genetic syndromes such as Kabuki syndrome and Thanatophoric dysplasia type I that are potentially associated with an increased NT. A cut-off of greater than the 95th percentile may be useful in case selection for ES. Whether it is clinically meaningful to monitor NF values for fetuses with isolated increased NT and normal chromosomes worth considering.