Jun 16 - Beyond the Common Aneuploidies: Optimal Diagnostic Workup and Counseling Following Positive cfDNA Screening OnDemand-Beyond the Common Aneuploidies PDF

Beyond the Common Aneuploidies PDF

Pdf Summary

This ACMG/ADLM educational webinar reviewed best practices for interpreting and following up on positive cfDNA screening results beyond common aneuploidies, including rare autosomal aneuploidies, sex chromosome conditions, and copy number variants. The session emphasized that cfDNA is a screening test based largely on placental DNA in maternal blood, so abnormal results can reflect fetal, placental, or maternal findings, and false positives may occur.<br /><br />Key topics included:<br />- When and how cfDNA screening is offered, and limitations related to fetal fraction, bioinformatic pipelines, and laboratory validation.<br />- The role of confirmatory diagnostic testing, including CVS, amniocentesis, cord blood, karyotype, FISH, and chromosomal microarray, with test selection guided by the suspected abnormality and timing.<br />- Case-based examples illustrating confined placental mosaicism, trisomy rescue, uniparental disomy, and maternal mosaicism.<br /><br />Cases highlighted:<br />- Trisomy 16 screening led to normal fetal karyotype but microarray evidence suggestive of UPD16 and later fetal growth restriction, demonstrating how placental abnormalities can affect pregnancy outcomes.<br />- 22q11.2 deletion screening showed the importance of counseling about low positive predictive value and appropriate fetal imaging and confirmatory testing.<br />- Monosomy X cases showed that cfDNA may detect fetal Turner syndrome, placental mosaicism, or maternal mosaicism; some results prompted maternal evaluation, including karyotype/FISH and broader Turner syndrome health surveillance.<br /><br />The webinar concluded that positive cfDNA results require careful pre- and post-test counseling, attention to positive predictive value and test limitations, thoughtful selection of confirmatory studies, fetal imaging when indicated, and multidisciplinary collaboration among maternal-fetal medicine specialists, genetic counselors, and laboratory professionals.

Keywords

cfDNA screening

positive screening results

aneuploidy

rare autosomal aneuploidies

sex chromosome conditions

copy number variants

confirmatory diagnostic testing

confined placental mosaicism

uniparental disomy

maternal mosaicism