Nephronophthisis

The disease presents as a tubulointerstitial nephropathy. While the kidneys can be solely affected, extrarenal manifestations occur in 10–40% of patients and may include:

• Retinitis pigmentosa ()
• Oculomotor apraxia (Cogan syndrome)
• Optic nerve coloboma and cerebellar vermis aplasia ()

The incidence in Europe is estimated at approximately 1:50,000.

Nephronophthisis is caused by a dysfunction of primary cilia. Pathogenic variants have so far been identified in more than 25 genes associated with NPHP. The most common cause of the juvenile form is a homozygous deletion of NPHP1, present in approximately 30–60% of patients.

Nephronophthisis is inherited in an autosomal recessive manner.

Diagnosis is based on clinical presentation, renal findings and molecular analysis. Nephronophthisis is phenotypically and genetically heterogeneous, and mutation analysis is extensive due to the large number of associated genes. About 40–60% of NPHP patients have no identifiable genetic cause.

Syndromic ciliopathies with renal involvement, particularly those presenting with retinal degeneration, cerebellar anomalies or oculomotor dysfunction.

Nephronophthisis is subdivided according to the typical age of onset of terminal renal failure:

• Infantile (<4 years)
• Juvenile (around 13 years)
• Adolescent/adult (around 19 years)

• Titieni et König 2018, medgen 30:461
• Luo et Tao 2018, Nephrology (Carlton) 23:904
• König et al. 2017, Clin J Am Soc Nephrol 12:1974
• Chaki et al. 2011, Kidney Int 80:1239
• Hoefele et al. 2007, Der Nephrologe 2:372
• Hildebrandt & Omran 2001, Pediatr Nephrol 16:168
• Hildebrandt et al. 1997, Kidney 51:261