Fetal Isolated Unilateral Multicystic Dysplastic Kidney Identified on Second Trimester Ultrasound: Genetic Investigation Results at a Single Referral Center

ABSTRACT Objective To investigate genetic defects in fetuses diagnosed with isolated unilateral multicystic dysplastic kidney (MCDK). Methods This retrospective study analyzed 138 cases of unilateral fetal MCDK identified through second‐trimester anatomical ultrasound examinations. Fourteen cases were excluded because of their association with extrarenal anomalies. All participants underwent invasive prenatal diagnostic procedures for copy number variant (CNV) detection via chromosomal microarray analysis (CMA). For those with negative CNV results, exome sequencing (ES) was offered as an add‐on diagnostic approach. Clinical and laboratory data were systematically collected and reviewed, encompassing maternal demographics, prenatal sonographic findings, molecular testing outcomes, and pregnancy results. Results Of the 124 cases with isolated unilateral MCDK, CMA identified two instances of sex chromosomal aneuploidy, five cases of pathogenic CNVs, and one case demonstrating a pathogenic region of homozygosity associated with Silver‐Russell Syndrome. The diagnostic yield for CNVs using CMA was found to be 4.8%. Among the patients who received negative CMA results, 73 proceeded to second‐trimester trio ES; no disease‐causing variants were detected. One case without prenatal ES developed bilateral ventriculomegaly in the third trimester; postnatal trio ES revealed a de novo likely pathogenic variant c.5138 G > A (p.Ser1713Asn) in the SCN1A gene. Conclusion The observed diagnostic yield of 4.8% for CNVs underscores the importance of utilizing CMA in pregnancies complicated by fetal isolated unilateral MCDK. Further research involving larger sample sizes is essential to enhance our understanding of the contribution of monogenic disorders to this condition.