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  • Review Article
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Inherited cerebrorenal syndromes

Nature Reviews Nephrology volume 5, pages 529–538 (2009)Cite this article

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.

Key Points

  • A number of rare conditions with defined genetic abnormalities are characterized by a set of specific cerebrorenal symptoms including Lowe syndrome, Joubert syndrome, and Bardet–Biedl syndrome

  • Lowe syndrome is an X-linked disorder that results from mutations in OCRL, a gene that encodes a phosphatase involved in endosomal trafficking

  • Boys with Lowe syndrome have Fanconi-type renal tubular dysfunction and progressive renal failure with developmental delay and blindness

  • Joubert syndrome is a genetically heterogeneous ciliopathy; affected patients can display cerebellar ataxia, pigmentary retinopathy and nephronophthisis

  • Bardet–Biedl syndrome is a clinically variable and genetically heterogeneous ciliopathy; patients can present with cystic and fibrotic renal changes that can lead to renal failure, along with learning disabilities, progressive vision loss, obesity, and hypogonadism

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Figure 1: Discoid cataract in an infant with Lowe syndrome.
Figure 2: A boy with the typical facies of Lowe syndrome.
Figure 3: Role of OCRL-1 in endosome and trans-Golgi network trafficking.
Figure 4: The 'molar tooth sign' associated with Joubert syndrome.
Figure 5: A girl with wide midface and upward nasal displacement characteristic of Bardet–Biedl syndrome.

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Acknowledgements

The authors are grateful to Dr. Thomas welch for helpful comments and to Michele O'Brien for manuscript preparation.

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

    Scott J. Schurman

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

    Steven J. Scheinman

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Schurman, S., Scheinman, S. Inherited cerebrorenal syndromes. Nat Rev Nephrol 5, 529–538 (2009). https://doi.org/10.1038/nrneph.2009.124

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