Juvenile Nephronophthisis

Juvenile nephronophthisis is an inherited disorder, which mainly affects children. Patients with this disease typically develop cysts and fibrosis in the kidney, which can leads to production of large volume of urine (polyuria), excessive liquid intake (polydipsia), and appearance of protein in the urine (proteinuria). Eventually, the symptom will progress to end-stage kidney disease, which will require dialysis or a kidney transplant in order for the patient to survive. Besides the kidney problems, some patients can also develop blindness, liver problems, severe global developmental delay or intellectual disability, and neurologic involvement in which the cerebellum is affected. This disease is caused by pathogenic variants in the NPHP1 gene.

Juvenile nephronophthisis is inherited in an autosomal recessive manner. Both parents must be carriers of a pathogenic variant in the gene in order to be at risk to have an affected child. This type of inheritance requires the presence of two copies of a pathogenic variant in the gene, one inherited from each carrier parent, for the child to have the genetic disease. There is a 1 in 4 chance that a baby will inherit two mutated copies of the gene and be affected when both parents are carriers.

There are generally no signs or symptoms associated with being a carrier for juvenile nephronophthisis. However, the risk to have a child affected with juvenile nephronophthisis is increased. Testing of reproductive partners is recommended for carriers of juvenile nephronophthisis.

The prevalence of juvenile nephronophthisis has not been determined. Currently, it is estimated that juvenile nephronophthisis occurs in between 1 in 50,000 and 1 in 900,000 newborns.

Genetic Home Reference: NPHP1 (http://ghr.nlm.nih.gov/)

OMIM [Nephronophthisis 1, juvenile: 256100] (http://www.ncbi.nlm.nih.gov/omim)

• Copy number analysis: 4, 11 & 20