Utility of fetal whole exome sequencing in the etiological evaluation and outcome of nonimmune hydrops fetalis. (2nd August 2021)

• Record Type: Journal Article
• Authors: Correa, Alec Reginald Errol; Naini, Kamal; Mishra, Pallavi; Dadhwal, Vatsla; Agarwal, Ramesh; Shukla, Rashmi; Kabra, Madhulika; Gupta, Neerja
• Is Part Of: Prenatal diagnosis. Volume 41:Number 11(2021)
• Page Start: 1414
• Page End: 1424
• Publication Date: 2021-08-02
• Subjects: Prenatal diagnosis -- Periodicals; Fetus -- Diseases -- Diagnosis -- Periodicals; Electronic journals; 618.32075
• DOI: 10.1002/pd.6022
• Languages: English
• ISSNs: 0197-3851

Abstract

Abstract: Introduction: Nonimmune hydrops fetalis (NIHF) has varied etiology. We assessed the etiological spectrum and evaluated the utility of fetal whole exome sequencing (fWES) for the diagnosis of NIHF. Methods: In this prospective cohort study, we evaluated antenatally diagnosed fetuses with NIHF between July 2018 and December 2019 according to the routine diagnostic algorithm. Fetuses that remained undiagnosed after routine NIHF workup were subjected to fetal chromosomal microarray and/or WES. Pregnancies were followed up for clinical outcomes. Results: Of the 45 fetuses, consanguinity and recurrent hydrops fetalis were observed in 13.3% (6/45) and 28.8% (13/45), respectively. Overall, an etiological diagnosis was possible in 75.5% (34/45) of fetuses, while the cause remained unknown in 24.4% (11/45). A genetic etiology was identified in 46.6% (21/45): aneuploidy and monogenic disorders in 28.8% (13/45) and 17.8% (8/45), respectively. fWES on 19 fetuses detected disease‐causing variants in 42.1% (8/19). Nine novel variants were detected in RAPSN, ASCC1, NEB, PKD1L1, GUSB, and PIEZO1 . Only 8.8% (4/45) of the cohort survived without morbidity. Conclusions: This study describes the etiological spectrum and the disease‐causing variants in an Indian cohort of hydropic fetuses. Key points: What's already known about this topic? Nonimmune hydrops fetalis (NIHF) has a varied etiology that includes both genetic and non‐genetic causes, and a significant number of cases remain undiagnosed. NIHF has a poor prognosis and is associated with high mortality. What does this study add? This study presents the etiological spectrum and outcome in an Indian cohort of NIHF. It describes the disease‐causing variants identified by fetal whole‐exome sequencing in this cohort. In a small percentage, NIHF may resolve spontaneously during pregnancy and carry a good prognosis.