A Pain in the Neck: Lessons Learnt from Genetic Testing in Fetuses Detected with Nuchal Fluid Collections, Increased Nuchal Translucency versus Cystic Hygroma—Systematic Review of the Literature, Meta-Analysis and Case Series

Fetal Nuchal fluid collections can manifest with two distinct presentations attributable to the same phenotypic spectrum: increased nuchal translucency (iNT) and cystic hygroma. The prenatal detection of these findings should prompt an accurate assessment through genetic counseling and testing, including karyotype, chromosomal microarray analysis (CMA) and multigene RASopathy panel. We performed a systematic review of the literature and meta-analysis, to calculate diagnostic yields of genetic testing in fetuses with iNT and cystic hygroma. We compared the results with a cohort of 96 fetuses with these isolated findings. Fetuses with isolated NT ≥ 2.5 mm showed karyotype anomalies in 22.76% of cases and CMA presented an incremental detection rate of 2.35%. Fetuses with isolated NT ≥ 3 mm presented aneuploidies in 14.36% of cases and CMA had an incremental detection rate of 3.89%. When the isolated NT measured at least 3.5 mm the diagnostic yield of karyotyping was 34.35%, the incremental CMA detection rate was 4.1%, the incremental diagnostic rate of the RASopathy panel was 1.44% and it was 2.44% for exome sequencing. Interestingly, CMA presents a considerable diagnostic yield in the group of fetuses with NT ≥ 3.5 mm. Similarly, exome sequencing appears to show promising results and could be considered after a negative CMA result.