Isolated hypospadias identified on fetal ultrasound: genetic investigation results at a single referral center.

Introduction To investigate genetic defects in fetuses diagnosed with isolated hypospadias. Methods This retrospective study analyzed 61 cases of isolated fetal hypospadias identified through second-trimester or third-trimester ultrasound examinations. All participants underwent invasive prenatal diagnostic procedures for copy number variant (CNV) detection via chromosomal microarray analysis (CMA). For those with normal CNV results, trio whole exome sequencing (WES) was offered as an alternative. Clinical and laboratory data were systematically collected and reviewed, encompassing maternal demographics, prenatal sonographic findings, molecular testing outcomes, and pregnancy results. Results Three cases of sex chromosomal mosaicism were identified. In the remaining 58 cases, all had the male karyotype. CMA detected only one case of pathogenic CNVs (2q13 microdeletion). Among the cases with normal CMA, 35 underwent trio WES; two had disease causing variants: one carried a de novo CREBBP variant, and one carried two SRD5A2 variants. Conclusions From our perspective, CMA and WES are valuable tools in antenatal care for isolated cases of hypospadias detected via ultrasound; this information should be communicated to patients through prenatal counseling.