P25 Discrepant prenatal and postnatal diagnostic testing identify an unsuspected diagnosis of trisomy 21 with atypical postnatal clinical features

Whole genome sequencing (WGS) (R27, paediatric disorders) was undertaken on a blood sample from a one-week-old girl presenting with ventricular septal defect, partial agenesis of the corpus callosum and talipes. WGS results indicated non-mosaic trisomy 21 in this patient and no additional reportable findings. This result was unexpected given the patient’s lack of typical Down’s syndrome dysmorphology. Additionally, this patient had been tested prenatally via amniotic fluid sampling at 21 weeks’ gestation. QF-PCR, SNP array and prenatal exome trio testing (R21) undertaken on the uncultured amniotic fluid sample had not detected any reportable genetic findings. Additional scrutiny of the prenatal QF-PCR and SNP array results confirmed there was no evidence of low-level mosaicism for trisomy 21. Genotype comparison of DNA from the uncultured amniocytes, postnatal blood and previously untested cultured amniocytes confirmed this to be a rare case of trisomy 21 mosaicism with discrepant prenatal and postnatal results, likely resulting from a postzygotic non-disjunction event. This case serves as a reminder that trisomy mosaicism cannot be fully excluded by standard diagnostic methods due to assay sensitivity and potentially very significantly different proportions of cell lines in different tissue types.