Renal cysts and diabetes syndrome

Congenital anomalies of the kidney and urinary tract (CAKUT) are observed in approximately 3-6 per 1,000 newborns and are the leading cause of chronic renal failure in childhood. CAKUT encompasses a wide spectrum of structural and functional malformations, resulting in defective morphogenesis of the kidneys and/or urinary tract. The phenotypic spectrum ranges from vesicoureteral reflux to renal agenesis.

Causative variants have been identified in approximately 50 genes associated with CAKUT, with the HNF1B and PAX2 genes most frequently affected (approximately 5% of cases).

HNF-1ß, a transcription factor, is considered an essential factor for the embryonic development of the kidneys, urinary tract, pancreas, and liver, and is encoded by the HNF1B gene. The clinical phenotype can vary greatly in the presence of a pathogenic HNF1B alteration, even within a family with carriers of the same causative alteration. Pathogenic HNF1B variants lead to a broad phenotypic spectrum of renal diseases or malformations such as renal hypoplasia, multicystic dysplastic kidneys (MCDK), solitary kidneys, and renal cysts, with the latter being one of the most frequent manifestations.

The simultaneous presence of renal cysts and diabetes is referred to as RCAD (renal cysts and diabetes) syndrome or MODY diabetes type 5.

References

Kosfeld et al. 2018, medgen 30:448 / Bockenhauer et Jaureguiberry 2016, Pediatr Nephrol 31:707 / Duval et al. 2016, Prenat Diagn 36:744 / Verhave et al. 2016, Am Soc Nephrol 27:345 / Clissold et al. 2015, Nat Rev Nephrol 11:102 / Bergmann et al. 2011, J AM Soc Nephrol 22:2047 / Saisawat et al. 2011, Kidney Int 81:196