The utility of genome‐wide cell‐free DNA screening in the prenatal diagnosis of Pallister‐Killian syndrome

Objective To report genome-wide cell-free DNA (cfDNA) screening facilitating the diagnosis of Pallister-Killian syndrome (PKS). Methods This is a retrospective cohort analysis of positive genome-wide cfDNA screening results showing increased signal from chromosome 12 and the detection of PKS. The genome-wide cfDNA screening results and the subsequent investigations were reviewed. Results Three singleton pregnancies (3/29007) from 2016 to 2017 yielded positive results indicating large gains on the entire p-arm of chromosome 12. In two cases, multiple structural abnormalities were detected by prenatal ultrasound and the couples opted for termination of pregnancy. Chromosomal microarray performed on fetal skin tissues of the two abortuses detected mosaic tetrasomy 12p, consistent with PKS. In the third case, karyotype and chromosomal microarray performed on an amniotic fluid sample also showed mosaic tetrasomy 12p. In each of the three cases, genome-wide cfDNA screening revealed a large gain on chromosome 12p; subsequent prenatal or postnatal diagnostic testing confirmed the diagnosis of PKS. Conclusion We report the ability of genome-wide cfDNA screening to provide early suspicion and facilitate the subsequent genetic diagnosis of PKS. As genome-wide cfDNA screening becomes increasingly available, incidental diagnosis of partial aneuploidies is expected to increase.