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Meta-Analysis
. 2023 May;103(5):503-512.
doi: 10.1111/cge.14309. Epub 2023 Feb 26.

Diagnostic yield from prenatal exome sequencing for non-immune hydrops fetalis: A systematic review and meta-analysis

Huda B Al-Kouatly  1 , Kavya Shivashankar  2 , Matthew H Mossayebi  3 , Mona Makhamreh  4 , Elizabeth Critchlow  3 , Zimeng Gao  5 , Luther-King Fasehun  6 , Fowzan S Alkuraya  7 , Erin E Ryan  8 , Madhuri Hegde  9 , Sascha Wodoslawsky  3 , Joel Hughes  10 , Seth I Berger  11
Affiliations
Meta-Analysis

Diagnostic yield from prenatal exome sequencing for non-immune hydrops fetalis: A systematic review and meta-analysis

Huda B Al-Kouatly et al. Clin Genet. 2023 May.

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.

Keywords: exome sequencing; non-immune hydrops fetalis; prenatal diagnosis; prenatal exome sequencing.

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References

REFERENCES

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