Nephronophthisis and Renal–Hepatic–Pancreatic Dysplasia of Ivemark

Abstract

Nephronophthisis is a disease of renal tubular dysfunction that progresses to end-stage renal disease; it can occur in combination with abnormalities of other organs including the liver. Growing knowledge of the genes associated with nephronophthisis indicates that the disease is associated with dysfunction of primary cilia and related structures. Renal hepatic pancreatic dysplasia of Ivemark is a rare, typically fatal congenital anomaly sequence, characterized by renal dysplasia, hepatic dysgenesis, and pancreatic fibrosis. Newer data suggest that it, too, is related to abnormalities of cilia and may share gene abnormalities with syndromes associated with nephronophthisis. Knowledge of the various genes involved in these and other cystic/dysplastic syndromes continues to grow. Diverse mutations in genes associated with the primary cilium can lead to a variety of phenotypes; epistasis and oligogenic inheritance may explain some of the variety in clinical findings.