Nephronophthisis and related syndromes

Curr Opin Pediatr. 2015 Apr;27(2):201-11. doi: 10.1097/MOP.0000000000000194.


Purpose of review: Nephronophthisis (NPHP) is an autosomal recessive cystic kidney disease and is one of the most common genetic disorders causing end-stage renal disease (ESRD) in children and adolescents. NPHP is a genetically heterogenous disorder with 20 identified genes. NPHP occurs as an isolated kidney disease, but approximately 15% of NPHP patients have additional extrarenal symptoms affecting other organs [e.g. eyes, liver, bones and central nervous system (CNS)]. The pleiotropy in NPHP is explained by the finding that almost all NPHP gene products share expression in primary cilia, a sensory organelle present in most mammalian cells. If extrarenal symptoms are present in addition to NPHP, these disorders are classified as NPHP-related ciliopathies (NPHP-RC). This review provides an update about recent advances in the field of NPHP-RC.

Recent findings: The identification of novel disease-causing genes has improved our understanding of the pathomechanisms contributing to NPHP-RC. Multiple interactions between different NPHP-RC gene products have been published and outline the interconnectivity of the affected proteins and shared pathways.

Summary: The significance of recently identified genes for NPHP-RC is discussed and the complex role and interaction of NPHP proteins in ciliary function and cellular signalling pathways is highlighted.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Adolescent
  • Child
  • Cilia / pathology*
  • Cilia / physiology
  • Cytoskeletal Proteins
  • Genes, Recessive
  • Humans
  • Kidney / pathology*
  • Kidney Diseases, Cystic / complications
  • Kidney Diseases, Cystic / congenital*
  • Kidney Diseases, Cystic / pathology
  • Kidney Diseases, Cystic / physiopathology
  • Kidney Failure, Chronic / etiology
  • Kidney Failure, Chronic / genetics
  • Kidney Failure, Chronic / pathology*
  • Kidney Failure, Chronic / physiopathology
  • Membrane Proteins / metabolism*
  • Mutation / genetics
  • Phenotype
  • Signal Transduction


  • Adaptor Proteins, Signal Transducing
  • Cytoskeletal Proteins
  • Membrane Proteins
  • NPHP1 protein, human

Supplementary concepts

  • Nephronophthisis, familial juvenile