Nephronophthisis is an autosomal recessive disorder that causes cysts restricted to the renal medulla or corticomedullary border, tubular dysfunction and, eventually, renal failure.
Nephronophthisis accounts for 10 to 20% of chronic renal failure in children and young adults (< 20 yr).
The first clinical signs are due to tubular injury that result in concentration defect and salt wastage. Polyuria and polydispsia follow. The net sodium loss probably accounts for lack of hypertension during progressive renal failure. Later on, growth retardation becomes apparent and progressive renal insufficiency develops. Several extrarenal manifestations have been associated with nephronophthisis. Some of them are syndromic and specifically named.
Ocular symptoms associated with nephronophthisis include Senior-Loken syndrome, Leber congenital amaurosis, coloboma, cataract, amblyopia, nystagmus, and retinitis pigmentosa. Nephronophthisis accompanied by tapeto-retinal degeneration is called Senior-Loken syndrome. Two forms of blindness exist. Leber congenital amaurosis is the early form, the children are blind from birth. The electroretinogram is extinct, and retinitis pigmentosa is the accompanying morphological finding. There also exists an late onset form in which blindness occurs later during childhood.
Cerebral symptoms accompanying nephronophthisis are usually also accompanied by retinal degeneration. The symptoms can lead to mental retardation and cerebellar ataxia. Two syndromes describe these symptoms: Cogan syndrome (oculomotor apraxia and hypoplasia of cerebellar vermix) and Joubert syndrome (cerebellar vermix hypoplasia, ataxia, hypotonia, developmental delay, and respiratory distress at birth).
Bon abnormalities present with cone-shaped epiphysis and are almost always associated with other extrarenal findings.
Hepatic changes include hepatospenomegaly and portal fibrosis without or with only mild duct proliferation.
Clinical signs are rather unspecific. Urinalysis shows few tubular abnormalities, but helps to exclude other renal disease. Family history (if present) provides further evidence but seldom allows to further differentiate the exact type of disease. As renal cysts become visible late in disease only, ultrasonography, CT, and MRI fail to provide an early diagnosis. Renal biopsy, though specific, is typically not performed because it is invasive. By contrast, molecular genetic testing is the only way to get an early, precise and non-invasive diagnosis.