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.
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.
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.
^page 831, Chapter 35, in: Avner, Ellis D.; Harmon, William; Niaudet, Patrick; Yoshikawa, Norishige. Pediatric Nephrology (Avner, Pediatric Nephrology). Springer. ISBN978-3-540-76327-7. (stating the incidence in the United States as 9 per 8.3 million people.