Next Generation Sequencing in a Case of Early Onset Hydrops: Closing the Loop on the Diagnostic Odyssey!

Non-immune fetal hydrops (NIFH) is an etiologically heterogeneous condition. Cardiac anomalies are one of the common causes of NIFH. Cardiac anomalies can be isolated, multifactorial malformations or have a genetic basis. variants have been associated with developmental defects involving the right heart. We present a NIFH with a associated right heart malformation. We describe a spontaneously aborted 14 weeks old NIFH fetus with a rudimentary right ventricle, pulmonary valve atresia and pulmonary artery stenosis found at fetopsy. After a normal microarray, whole exome sequencing revealed a homozygous missense variant c.2023 C > T (p. Arg675Trp) in the gene. Detailed fetopsy and genetic evaluation in this NIFH allowed an etiological explanation, further corroborated the association of gene variants and developmental right heart defects, and that this defect can be associated with NIHF.