From the Guidelines
Increased nuchal translucency is a significant marker for potential chromosomal or genetic abnormalities, and further investigation is warranted, even with normal exome sequencing results, to rule out conditions such as Noonan syndrome and 22q11.2 deletion syndrome 1. The presence of increased nuchal translucency, defined as a measurement of ≥ 3 mm, places the fetus at sufficient risk for chromosomal abnormalities, with about one-third of fetuses having a chromosomal abnormality, and half of these being trisomy 21 1. Key considerations in the management of increased nuchal translucency include:
- Offering invasive diagnostic testing, such as chorionic villus sampling, to definitively rule out chromosomal abnormalities 1
- Performing a detailed fetal anatomy scan at 18-22 weeks gestation to identify potential structural abnormalities 1
- Considering fetal echocardiography at 20-22 weeks to evaluate cardiac structure and function, as the risk of congenital heart disease is elevated in fetuses with increased nuchal translucency 1
- Continuing regular prenatal care and monitoring throughout pregnancy, with serial fetal surveillance to monitor fetal growth and well-being 1
- Providing genetic counseling to discuss implications and potential outcomes, including the possibility of genetic syndromes such as Noonan syndrome, which may be detected through targeted genetic studies, including microarray analysis 1. It is essential to note that normal exome sequencing results do not rule out all potential genetic abnormalities, and further testing, such as microarray analysis, may be necessary to detect certain genetic conditions 1.
From the Research
Significance of Increased Nuchal Translucency
- Increased nuchal translucency (NT) is associated with an increased risk for genetic disorders 2, 3, 4, 5, 6
- The risk of adverse pregnancy outcome, including aneuploidy, other genetic disorders, structural anomalies, and pregnancy loss, is higher in fetuses with increased NT 6
Exome Sequencing Results
- Whole-exome sequencing (WES) can detect genetic abnormalities in fetuses with increased NT, with a diagnostic rate of 4.8% to 5.5% 2, 3
- The diagnostic yield of WES is higher in fetuses with additional structural anomalies, with a diagnostic rate of 22.2% to 32.4% 5
- WES can identify pathogenic variants, including single-nucleotide variants, copy number variants, and structural rearrangements 4
Factors Affecting Diagnostic Yield
- The presence of additional structural abnormalities increases the diagnostic yield of WES 5
- The size of NT measurement also affects the diagnostic yield, with larger NT measurements associated with a higher diagnostic rate 5
- Early detailed ultrasound to detect emerging anomalies can help physicians offer prenatal WES to fetuses with a greater likelihood of diagnosis 2
Clinical Implications
- Prenatal WES may not be appropriate for truly isolated increased NT, but may be considered for fetuses with additional structural anomalies or larger NT measurements 5
- Invasive prenatal testing should be offered if an increased NT of ≥ 2.5 mm is observed before 11 weeks' gestation 6
- Expectant parents should be referred to a fetal medicine unit for detailed ultrasonography if an increased NT is detected 6