879: Utility of chromosomal microarray in cases of non-immune hydrops fetalis

Abstract

We sought to determine the yield of whole exome sequencing (WES) in determining the genetic etiology of fetal pleural effusions. STUDY DESIGN: We examined a retrospective cohort series of all cases of fetal pleural effusions visualized by prenatal ultrasound at a single center between May 1, 2016 and May 31, 2017. Prenatal and postnatal medical records were examined for clinical presentation and diagnostic workup. Fetal pleural effusions attributed to twin sharing, red cell alloimmunization, or structural anomalies were excluded, as were cases with a genetic diagnosis confirmed by karyotype or microarray analysis. The remaining cases were offered WES. WES was performed on cases submitted for either clinical sequencing or sequencing under the Baylor-Hopkins Center for Mendelian Genomics' research sequencing platform. RESULTS: Twenty-four fetuses with pleural effusions were evaluated by prenatal ultrasound. Eleven cases (45.8%) were excluded due to twin-transfusion (3 cases), twin anemia polycythemia sequence (1 case), Rh disease (2 cases), congenital diaphragmatic hernia (2 cases), cystic pulmonary airway malformation (1 case), and fetal teratoma (2 cases). Six additional cases (25%) were excluded due to diagnoses of monosomy X (4 cases), trisomy 21 (1 case), and terminal 7q36 deletion/7p22 duplication (1 case). Of the remaining 7 cases, 5 underwent WES, including 3 parent-proband trios and 2 parent-proband-affected sibling quads. We identified a pathogenic variant in 1 case, a likely pathogenic variant in a second case, and 3 cases with variants of unknown significance with potential for reclassification based on expansion of phenotype (see table). CONCLUSION: Following standard clinical evaluations, a causative etiology remained unknown in 29.2% of prenatally diagnosed pleural effusions. In the present series, WES identified a pathogenic variant in 20% of such cases. Additional variants identified by WES require validation studies for confirmation. WES should be considered in cases of fetal pleural effusions when the standard evaluation is not diagnostic.