The Clinical Utility of Sequence-Based Genetic Testing for Fetal Edema Following Non-Diagnostic Microarray Results: A
Victoria M Allen1,2, Heleen H Arts1,2, Erica Schollenberg1,2
1Dalhousie University, Halifax, NS, Canada.
Prenatal Diagnosis
|March 3, 2026
Summary
Further genetic sequencing after non-diagnostic microarray testing for fetal edema identified genetic disorders in 34% of cases. RASopathy panel sequencing is recommended for increased nuchal translucency or cystic hygroma.
Area of Science:
- Medical Genetics
- Prenatal Diagnosis
- Fetal Medicine
Background:
- Fetal edema identified via ultrasound can indicate underlying genetic disorders.
- Chromosomal microarray (CMA) is a primary genetic test, but may not yield a diagnosis in all cases of fetal edema.
Purpose of the Study:
- To assess the frequency and diagnostic yield of further genetic sequencing in fetuses with edema after a non-diagnostic CMA.
- To evaluate the utility of targeted gene panels and exome sequencing in this specific population.
Main Methods:
- Retrospective review of 114 cases with fetal edema and non-diagnostic CMA results from 2014-2022.
- Analysis of genetic testing utilization (targeted genes, panels, exomes) following multidisciplinary review.
- Descriptive analysis to determine diagnostic yields based on specific ultrasound findings and testing types.
Main Results:
- Genetic diagnoses were achieved in 17 (34%) of the 114 cases.
- RASopathy testing yielded 18.5% diagnostic rate, while exome sequencing achieved 41.2%.
- Highest diagnostic yields were observed in cases with fetal hydrops and isolated fetal edema.
Conclusions:
- Targeted sequencing, particularly RASopathy panels, offers significant diagnostic yield for fetal edema with increased nuchal translucency or cystic hygroma, and should be considered standard care alongside CMA.
- Multidisciplinary review and correlation of prenatal/postnatal findings are crucial for guiding further testing, genetic counseling, and management, especially in non-immune fetal hydrops.
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