926: Mosaic trisomy 2 identified via whole-genome cfDNA screening

Esoteric aneuploidy (non-trisomy 13/18/21) detection via expanded cfDNA prenatal screening presents several unique caveats; they are relatively common, often confined to the placenta, and have variable clinical impact. Herein we describe one of very few clinical reports of mosaic trisomy 2, in addition to the first and only cfDNA identified case of a true fetal mosaic trisomy 2 in the medical genetic literature. The maternal blood sample was subjected to DNA extraction, library preparation, and genome-wide massively parallel sequencing. Sequencing data were analyzed using a novel algorithm to detect trisomies and subchromosomal, genome-wide copy number variants 7Mb and larger. The patient presented to MFM at 10.7 weeks’ gestation for genetic counseling and ultrasound. AMA and a prior trisomy 8 pregnancy prompted expanded cfDNA screening, yielding a trisomy 2 result (∼ 65% mosaicism, 6% fetal fraction) and residual risk for UPD. Amnio with SNP microarray testing was recommended. Trisomy 2 is a relatively common finding per placental literature, usually confined to the mesenchyme, and carries an exceedingly low risk for true fetal mosaicism. A paucity of published trisomy 2 case studies was a substantial counseling limitation. CVS was declined and fetal ultrasound showed normal growth and NT measurement at 10.7 weeks. However, a subsequent scan at 16 weeks showed a 2 vessel cord and a 1 week lag in humerus/femur length, increasing to a 2 week lag by 18 wks. Fetal echo showed hypoplastic LVOT and possible coarch of the aorta. Amnio at 20 weeks with SNP microarray revealed ∼20% mosaicism for Trisomy 2, no UPD. Pregnancy continued with growth lag measuring 5 weeks behind at 33 weeks. Palliative care was discussed, as prognosis was guarded. PROM at 34.4 weeks prompted delivery of a 3lbs, 6oz (0%) neonate with APGARs of 2 and 8. An extended NICU stay ensued, with clinical outcome exceeding expectations. ASD repair occurred at 10 months. Now age three, the child is reportedly doing well overall, with physical exam noting small size, axial hypotonia, and motor delays. While many esoteric trisomies remain confined to the placenta and are of variable clinical consequence, the risk for true and occult fetal mosaicism cannot be dismissed. This case report illustrates the first known cfDNA identified, amnio confirmed true fetal mosaic for trisomy 2.