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.

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

Symptoms
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, and neurologic involvement in which the cerebellum is affected.

Histology
Histologically, nephronophthisis is characterized by fibrosis and the formation of cysts in a specific region of the kidney. 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.

Pathophysiology


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
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.