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

Abstract

Background:

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. PLD1 variants have been associated with developmental defects involving the right heart. We present a NIFH with a PLD1 associated right heart malformation.

Case report:

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 PLD1 gene. Conclusion: Detailed fetopsy and genetic evaluation in this NIFH allowed an etiological explanation, further corroborated the association of PLD1 gene variants and developmental right heart defects, and that this defect can be associated with NIHF.

Keywords:

• PLD1
• right heart developmental defect
• non-immune fetal hydrops
• exome sequencing
• fetal autopsy

Acknowledgement

Authors are thankful to the family for participation in the study. Authors would like to acknowledge funding support from [Department of health research start up] Grant No:[R.12020/05/2020-HR]

Declaration of interest

No potential competing interest.

Additional information

Funding

Funding support from Department of health research start up Grant No: R.12020/05/2020-HR.