Diagnostic yield from prenatal exome sequencing for non‐immune hydrops fetalis: A systematic review and meta‐analysis. Issue 5 (26th February 2023)

• Record Type: Journal Article
• Authors: Al‐Kouatly, Huda B.; Shivashankar, Kavya; Mossayebi, Matthew H.; Makhamreh, Mona; Critchlow, Elizabeth; Gao, Zimeng; Fasehun, Luther‐King; Alkuraya, Fowzan S.; Ryan, Erin E.; Hegde, Madhuri; Wodoslawsky, Sascha; Hughes, Joel; Berger, Seth I.
• Is Part Of: Clinical genetics. Volume 103:Issue 5(2023)
• Page Start: 503
• Page End: 512
• Publication Date: 2023-02-26
• Subjects: exome sequencing -- non‐immune hydrops fetalis -- prenatal diagnosis -- prenatal exome sequencing; Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/cge.14309
• Languages: English
• ISSNs: 0009-9163

Abstract

Abstract: Non‐immune hydrops fetalis (NIHF) has multiple genetic etiologies diagnosable by exome sequencing (ES). We evaluated the yield of prenatal ES for NIHF, and the contribution of additional clinical findings and history. Systematic review was performed with PROSPERO tag 232951 using CINAHL, PubMed, and Ovid MEDLINE from January 1, 2000 through December 1, 2021. Selected studies performed ES to augment standard prenatal diagnostic approaches. Cases meeting a strict NIHF phenotype were tabulated with structured data imputed from papers or requested from authors. Genetic variants and diagnostic outcomes were harmonized across studies using current ACMG and ClinGen variant classification guidelines. Thirty‐one studies reporting 445 NIHF cases had a 37% (95% CI: 32%–41%) diagnostic rate. There was no significant difference between isolated NIHF and NIHF with fetal malformations or between recurrent and simplex cases. Diagnostic rate was higher for consanguineous than non‐consanguineous cases. Disease categories included RASopathies (24%), neuromuscular (21%), metabolic (17%), lymphatic (13%), other syndromes (9%), cardiovascular (5%), hematologic (2%), skeletal (2%), and other categories (7%). Inheritance patterns included recessive (55%), dominant (41%), and X‐linked (4%). ES should be considered in the diagnostic workup of NIHF with and without associated ultrasound findings regardless of history of recurrence or consanguinity. Abstract : Systematic review and meta‐analysis of prenatal exome sequencing studies reporting 445 cases of non‐immune hydrops fetalis (NIHF) shows an overall diagnostic yield of 37% regardless of presence or absence of major structural abnormalities. Prenatal exome sequencing for NIHF clarifies clinical disease categories, inheritance, and recurrence risks, all of which can help direct counseling and management.