Joubert Syndrome 4 / Juvenile Nephronophthisis-1 / Senior-Loken Syndrome-1 (NPHP1)

NPHP1-related ciliopathies include three different overlapping disorders, known as Joubert syndrome 4, juvenile nephronophthisis 1, and Senior-Loken Syndrome 1. All diseases are inherited in an autosomal recessive manner and are caused by pathogenic variants in the gene NPHP1.

  • Joubert Syndrome 4 is characterized by a distinct “molar tooth” sign on brain imaging. The clinical symptoms may include mild intellectual disability, abnormal eye movements, hypotonia, head tilt in infancy, and nephronophthisis with progressive kidney disease.
  • Juvenile nephronophthisis-1 is characterized by nephronophthisis which may progress to end stage renal failure. Other symptoms may include liver fibrosis, situs inversus, or cardiac malformations. Without treatment to prevent progression to end-stage renal failure, life expectancy would be significantly reduced.
  • Senior-Loken Syndrome-1 is characterized by nephronophthisis and features of Leber congenital amaurosis. Affected individuals may develop early and severe vision loss. The clinical prognosis depends on the severity of renal complications as end-stage renal failure is the major cause of death.

No clear genotype-phenotype correlation has been established.

For information about carrier frequency and residual risk, please see the residual risk table.

This gene is included on the following panel(s):