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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. 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.[1]

Its incidence has been estimated to be 0.9 per million people in the United States, and 1 in 50.000 births in Canada.[2]


Infantile, juvenile, and adolescent forms of nephronophthisis have been identified. Although the range of characterizations is broad, patients typically present with polyuria (production of large volume of urine), polydipsia (excessive liquid intake), and mild proteinuria (the abnormal appearance of protein in the urine), and after several months to years, end-stage kidney disease, a condition necessitating either dialysis or a kidney transplant in order to survive.

Approximately 10% of individuals with nephronophthisis also have so-called "extra-renal symptoms" which can include blindness, liver problems, severe global developmental delay or mental retardation, bleeding from nose,and neurologic involvement in which the cerebellum is affected.


Histologically, nephronophthisis is characterized by fibrosis and the formation of cysts at the cortico-medullary junction. In contrast to other cystic diseases of the kidney in which the kidneys are larger than usual, in nephronophthisis the kidneys are small to normal in size.


Nephronophthisis has an autosomal recessive pattern of inheritance.

From sequencing the DNA of individuals and families with nephronophthisis, scientists have identified thus far 8 different genes in which mutations can cause the disease. These genes are called NPHP1, NPHP2, NPHP3, NPHP4, NPHP5, NPHP6, NPHP7, and NPHP8, and the proteins for which they encode are known as the nephrocystins. Although the biological function of these proteins is not yet known, they all localize at least in part to an organelle in the cell called the primary cilia.

Relation to other 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. Thus, 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. 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 NPHP6 are sometime seen with retinitis pigmentosa, this particular association has a name senior lokin syndrome. [3]


  1. ^ 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. 
  2. ^ 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.
  3. ^ Badano, Jose L.; Norimasa Mitsuma; Phil L. Beales; Nicholas Katsanis (Sep 2006). "The Ciliopathies : An Emerging Class of Human Genetic Disorders". Annual Review of Genomics and Human Genetics 7: 125–148. doi:10.1146/annurev.genom.7.080505.115610. PMID 16722803. Retrieved 2008-06-15.