Testing for Noonan syndrome after increased nuchal translucency

Area of Science:

• Prenatal diagnostics
• Medical genetics
• Fetal medicine

Background:

• Increased nuchal translucency (NT) is a common first-trimester ultrasound finding.
• Noonan syndrome (NS) is a genetic disorder with variable clinical manifestations.
• The association between increased NT and NS in euploid fetuses requires further clarification.

Purpose of the Study:

• To determine the prevalence of Noonan syndrome (NS) in fetuses with increased NT.
• To assess the diagnostic yield of genetic testing for NS in this cohort.

Main Methods:

• Retrospective chart review of fetuses with first-trimester NT measurement ≥3 mm.
• Inclusion criteria: normal karyotype (CVS or amniocentesis) and prenatal genetic testing for NS.
• Genetic testing results were categorized as positive (pathogenic variants) or negative (unknown significance or no variants).

Main Results:

• 804 fetuses had NT ≥3 mm; 302 underwent karyotyping, with 200 showing normal results.
• Of 39 euploid fetuses tested for NS, four (10.3%) had pathogenic variants consistent with NS.
• Fetuses tested for NS had a median NT of 4.0 mm, compared to 4.3 mm in those not tested (p=0.05).

Conclusions:

• In euploid fetuses, an increased NT measurement is associated with a significant risk of Noonan syndrome.
• Genetic testing for NS should be considered in fetuses with increased NT and normal karyotype.
• This finding aids in genetic counseling and management of pregnancies with increased NT.