Why atypical findings matter: Follow up testing finds diagnostic results related to cfDNA screen

Fetal or maternal chromosomal abnormalities — copy number variation, aneuploidy, rearrangements, uniparental disomy — underlying an atypical screening signal

Ten years of FISH, karyotype and chromosomal microarray results, performed on prenatal, newborn or maternal samples, were matched to previous cell-free DNA screens with atypical results, generating 204 index cases. A diagnostic finding was obtained in 102 of 204 cases, and 87 of those 102 abnormalities were related to the atypical screening signal. Of these, 55 were pathogenic, 18 were variants of uncertain significance and 8 were likely benign. Copy number variation was the most common finding (38/102), followed by aneuploidy (37/102) and chromosome rearrangements (20/102); uniparental disomy and consanguinity were also detected.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

One in two atypical cell-free DNA results leads to a diagnostic abnormality: far too high a yield to simply reassure and defer. The authors' request that laboratories specify the suspected origin and type of abnormality is the right one, since that is what guides the choice between karyotype, microarray and maternal testing. Also worth noting is the detection of abnormalities in the pregnant person themselves, a possibility that should be anticipated in pre-screening counselling.

Analysis by Dr Thibaut Benquey