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Nephronophthisis has an autosomal recessive pattern of inheritance.
Classification and external resources
Specialty medical genetics
ICD-10 Q61.8
ICD-9-CM 753.16
OMIM 256100
DiseasesDB 29224
Patient UK Nephronophthisis

Nephronophthisis is a genetic disorder of the kidneys which affects children.[1] It is classified as a medullary cystic kidney disease. The disorder is inherited in an autosomal recessive fashion and, although rare, is the most common genetic cause of childhood kidney failure. It is a form of ciliopathy.[2] Its incidence has been estimated to be 0.9 cases per million people in the United States, and 1 in 50,000 births in Canada.[3]

Signs and symptoms[edit]

Infantile, juvenile, and adolescent forms of nephronophthisis have been identified. Although the range of characterizations is broad, people affected by nephronophthisis typically present with polyuria (production of a large volume of urine), polydipsia (excessive liquid intake), and after several months to years, end-stage kidney disease, a condition necessitating either dialysis or a kidney transplant in order to survive.[4] Some individuals that suffer from nephronophthisis also have so-called "extra-renal symptoms" which can include tapetoretinal degeneration, liver problems, ocularmotor apraxia, and cone-shaped epiphysis (Saldino-Mainzer syndrome).[5][6]


Nephronophthisis is characterized by fibrosis and the formation of cysts at the cortico-medullary junction, it is an autosomal recessive disorder which eventually leads to terminal kidney failure.[7]


Ciliopathy (eukaryotic cilium diagram)

Mechanism of nephronophthisis indicates that all proteins mutated in cystic kidney diseases express themselves in primary cilia. NPHP gene mutations cause defects in signaling resulting in flaws of planar cell polarity. The ciliary theory indicates that multiple organs are involved in NPHP (retinal degeneration, cerebellar hypoplasia, liver fibrosis, and intellectual disability).[8]

Related rare genetic disorders[edit]

Recent findings in genetic research have suggested that a large number of genetic disorders, both genetic syndromes and genetic diseases, that were not previously identified in the medical literature as related, may be, in fact, highly related in the genetypical root cause of the widely varying, phenotypically-observed disorders.[medical citation needed] Nephronophthisis is a ciliopathy. Other known ciliopathies include primary ciliary dyskinesia, Bardet-Biedl syndrome, polycystic kidney and liver disease, Alstrom syndrome, Meckel-Gruber syndrome and some forms of retinal degeneration.[9]

NPHP2 is infantile type of nephropthisis and sometimes associated with situs inversus this can be explained by its relation with inversin gene. NPHP1, NPHP3, NPHP4, NPHP5, and NPHP6 are sometimes seen with retinitis pigmentosa, this particular association has a name, senior lokin syndrome.[10]


Epidemiologically speaking, nephronophthisis, occurs equally in both sexes, and has an estimate 9 in about 8 million rate in individuals. Nephronophthisis is the leading monogenic cause of end-stage renal disease.[11]


  1. ^ "Nephronophthisis". Genetics Home Reference. Retrieved 2015-08-08. 
  2. ^ Hurd TW, Hildebrandt F (2011). "Mechanisms of nephronophthisis and related ciliopathies". Nephron Exp. Nephrol. 118 (1): e9–e14. doi:10.1159/000320888. PMC 2992643. PMID 21071979. 
  3. ^ page 831, Chapter 35, in: Avner, Ellis D.; Harmon, William; Niaudet, Patrick; Yoshikawa, Norishige. Pediatric Nephrology (Avner, Pediatric Nephrology). Springer. ISBN 978-3-540-76327-7.  (stating the incidence in the United States as 9 per 8.3 million people.
  4. ^ Hildebrandt, Friedhelm; Zhou, Weibin (2007). "Nephronophthisis-Associated Ciliopathies". Journal of the American Society of Nephrology 18 (6): 1855–71. doi:10.1681/ASN.2006121344. PMID 17513324. 
  5. ^ Kanwal, Kher (2007). Clinical Pediatric Nephrology, Second Edition (2nd ed.). McGraw-Hill. p. 205. ISBN 978-1-84184-447-3. Retrieved 9 August 2015. 
  6. ^ Medullary Cystic Disease~clinical at eMedicine
  7. ^ Salomon, Rémi; Saunier, Sophie; Niaudet, Patrick (2009). "Nephronophthisis". Pediatric Nephrology 24 (12): 2333–44. doi:10.1007/s00467-008-0840-z. PMC 2770134. PMID 18607645. 
  8. ^ Hildebrandt, Friedhelm; Attanasio, Massimo; Otto, Edgar (2009). "Nephronophthisis: Disease Mechanisms of a Ciliopathy". Journal of the American Society of Nephrology 20 (1): 23–35. doi:10.1681/ASN.2008050456. PMC 2807379. PMID 19118152. 
  9. ^ McCormack, Francis X.; Panos, Ralph J.; Trapnell, Bruce C. (2010-03-10). Molecular Basis of Pulmonary Disease: Insights from Rare Lung Disorders. Springer Science & Business Media. ISBN 9781597453844. 
  10. ^ Badano, Jose L.; Mitsuma, Norimasa; Beales, Phil L.; Katsanis, Nicholas (2006). "The Ciliopathies: An Emerging Class of Human Genetic Disorders". Annual Review of Genomics and Human Genetics 7: 125–48. doi:10.1146/annurev.genom.7.080505.115610. PMID 16722803. 
  11. ^ Hildebrandt, Friedhelm (2009). "Nephronophthisis". In Lifton, Richard P.; Somlo, Stefan; Giebisch, Gerhard H.; et al. Genetic Diseases of the Kidney. Academic Press. pp. 425–46. ISBN 978-0-08-092427-4. 

Further reading[edit]