Understanding the Limitations of Circulating Cell Free Fetal DNA: An Example of Two Unique Cases

Area of Science:

• Genetics
• Prenatal Diagnostics
• Molecular Biology

Background:

• Circulating cell-free fetal DNA (cffDNA) analysis is a widely used non-invasive screening method for fetal aneuploidies.
• While highly accurate, cffDNA screening is subject to false positive and false negative results.
• Understanding the circumstances leading to inaccurate cffDNA results is crucial for clinical management.

Purpose of the Study:

• To report and analyze two distinct cases of false positive circulating cell-free fetal DNA screening results.
• To emphasize the clinical scenarios where diagnostic confirmation is essential following cffDNA screening.
• To underscore the limitations of cffDNA as a standalone diagnostic test.

Main Methods:

• Case report analysis of two pregnant patients undergoing cffDNA screening.
• Review of diagnostic procedures including cytogenetic analysis (e.g., amniocentesis) and ultrasound findings.
• Correlation of cffDNA results with confirmed diagnoses.

Main Results:

• Case 1: cffDNA positive for trisomy 18, but subsequent maternal diagnosis revealed mosaicism for chromosome 18, with a normal fetal karyotype.
• Case 2: cffDNA positive for trisomy 13 in a patient with anomalous fetal ultrasound; amniocentesis identified a chromosome 8p duplication/deletion.
• Both cases illustrate discrepancies between cffDNA screening and definitive diagnostic testing outcomes.

Conclusions:

• False positive results in cffDNA screening can occur and may lead to unnecessary patient anxiety or interventions.
• Diagnostic testing, such as karyotyping via amniocentesis, remains critical for confirming or refuting cffDNA screening findings.
• Clinicians must be aware of cffDNA test limitations and integrate screening results with comprehensive clinical and ultrasound evaluations.