Abstract

Abnormalities in the central nervous system and renal function are seen together in a variety of congenital syndromes. This Review examines the clinical presentation and the genetic basis of several such syndromes. The X-linked oculocerebrorenal syndrome of Lowe is characterized by developmental delay, blindness, renal tubular dysfunction, and progressive renal failure. This syndrome results from mutations in the OCRL gene, which encodes a phosphatase involved in endosomal trafficking. Mutations in OCRL also occur in Dent disease, which has a milder disease phenotype than Lowe syndrome. Patients with Joubert syndrome have cerebellar ataxia, pigmentary retinopathy, and nephronophthisis. Joubert syndrome is a genetically heterogeneous condition associated with mutations in at least five genes that encode ciliary proteins. Bardet–Biedl syndrome is a clinically variable condition associated with learning disabilities, progressive visual loss, obesity, polydactyly, hypogonadism, and cystic and fibrotic renal changes that can lead to renal failure. Most of the 12 genes mutated in Bardet–Biedl syndrome are also involved in ciliary function, as are the genes implicated in other 'ciliopathies' with similar phenotypes, including Meckel syndrome.

Author affiliations

1. Departments of Pediatrics and Medicine, SUNY Upstate Medical University, Syracuse, NY, USA.
2. Departments of Medicine, SUNY Upstate Medical University, Syracuse, NY, USA.

Correspondence to: S. J. Scheinman, Office of the Dean, Upstate Medical University, 750 E. Adams Street, Syracuse, NY 13210, USA
Email: scheinms@upstate.edu