Prenatal Diagnosis of Vesicoureteral Reflux: Role of Combined Ultrasound Study and Next Generation Sequencing in Clinical Characterization. The Application of NGS in Prenatal Diagnosis

Background: Pathophysiology and clinical prognosis of congenital anomalies of the kidney and urinary tract are known, especially in adult. Recent studies using massively sequencing approach in adult are clarifying genetic basis of these pathologies. Moreover a great attention is turning to antenatal diagnosis of kidney and urinary anomalies, as this could improve the prognosis after birth. Methods: Next Generation Sequencing methods, using extensive gene panel (4,800 genes) combined to pipeline for analysis and variant prioritization suited for prenatal diagnosis. Results: we report a case of genetic and clinical characterization for fetal megacystis, revealed by ultrasound scan at 12 weeks of gestation. SOX17 gene variant, identified as causative for fetal megacystis, is already known for its pathogenic role in adult but was never described associated to fetal development. Furthermore, we introduce a Next Generation Sequencing method for a large number of disorders/genes analysis, with low incidental findings and variants of unknown significance risk, hence compatible to prenatal diagnosis. Conclusions: In our study we showed the relevance of genetic characterizing of ultrasound sign, for clinical definition and good clinical management immediately after birth. The absence of any genetic diagnosis often precludes clinical interpretation and definition of fetal megacystis, since it may be associated to several disorders and genetic/chromosomal anomalies, with different pathological effects, also involving neuronal development. In these cases it is very challenging to determine the prognosis and pregnancy risks.