Objective: Determine the incremental yield of prenatal exome sequencing (PES) over chromosome microarray (CMA) and/or karyotype for urinary tract malformations (UTMs).
Method: A prospective cohort study encompassing data from the English Genomic Medicine Service North Thames Laboratory Hub for fetuses with bilateral echogenic kidneys (BEKs) was combined with data from a systematic review. MEDLINE, EMBASE, Web of Science, MedRxiv and GreyLit were searched from 01/2010-02/2023 for studies reporting on the yield of PES over CMA or karyotype in fetuses with UTMs. Pooled incremental yield was determined using a random effects model. PROSPERO CRD42023364544.
Results: Fourteen studies (410 cases) were included. The incremental yield for multisystem UTMs, any isolated UTMs, and BEKs was 31% [95% CI, 18%-46%; I2 = 78%], 16% [95% CI, 6%-26%; I2 = 80%] and 51% [95% CI, 27%-75%; I2 = 34%]. The most common clinical diseases and syndromes identified, based on the variant genes detected, were Bardet-Biedl syndrome (BBS genes), dominant and recessive polycystic kidney diseases (PKD1, PKD2 and PKHD1) and renal cysts and diabetes syndrome (HNF1B).
Conclusion: There was a notable incremental genetic diagnostic yield when PES was applied to multisystem UTMs and BEKs. There was a modest incremental yield when this technique was used for UTMs other than BEKs.
© 2023 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.