The genetic etiologies of bilateral renal agenesis

ObjectiveThe goal of this study was to review and analyze the medical literature for cases of prenatal and/or postnatally diagnosed bilateral renal agenesis (BRA) and create a comprehensive summary of the genetic etiologies known to be associated with this condition.MethodsA literature search was conducted as a scoping review employing Online Mendeliain Inheritance in Man, PubMed, and Cochrane to identify cases of BRA with known underlying genetic (chromosomal vs. single gene) etiologies and those described in syndromes without any known genetic etiology. The cases were further categorized as isolated versus non-isolated, describing additional findings reported prenatally, postnatally, and postmortem. Inheritance pattern was also documented when appropriate in addition to the reported timing of diagnosis and sex.ResultsWe identified six cytogenetic abnormalities and 21 genes responsible for 20 single gene disorders associated with BRA. Five genes have been reported to associate with BRA without other renal anomalies; sixteen others associate with both BRA as well as unilateral renal agenesis. Six clinically recognized syndromes/associations were identified with an unknown underlying genetic etiology. Genetic etiologies of BRA are often phenotypically expressed as other urogenital anomalies as well as complex multi-system syndromes.ConclusionMultiple genetic etiologies of BRA have been described, including cytogenetic abnormalities and monogenic syndromes. The current era of the utilization of exome and genome-wide sequencing is likely to significantly expand our understanding of the underlying genetic architecture of BRA. What is already known about this topic?Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) are associated with a number of cytogenetic and over 75 single gene disorders.CAKUT genes associated with renal agenesis often present with other types of renal anomalies.Identifying genetic disorders that may present on prenatal ultrasound with bilateral renal agenesis (BRA) is important for counseling on prognosis, recurrence risk, and antenatal as well as postnatal management and therapeutic options.What does this review add?Genetic disorders associated with BRA specifically were determined through a comprehensive and up-to-date literature review.We assimilated the known genetic etiologies, both cytogenetic and single genes, for BRA to assist clinicians in their diagnostic work up when BRA is encountered prenatally.The study also explicates emerging knowledge about the roles of these genes in the fascinating interplay of processes that takes place during normal urinary tract development.