Nephronophthisis has an insidious onset and results from mutations in the NPHP genes. The ensuing tubulointerstitial nephritis can induce acute or chronic renal insufficiency and subsequently progress to end-stage kidney disease before the age of 20. Most patients present when the renal failure is in an advanced stage .
Depending on the onset of end-stage kidney disease, nephronophthisis has been divided into three clinical variants: infantile, juvenile, and adolescent .
The earliest symptoms are mild and can manifest in infancy or childhood as polyuria, polydipsia, secondary enuresis due to an impaired concentrating ability, and anemia. Additional features that may be observed include neurological disorders, liver fibrosis, and obesity.
Retinitis pigmentosa initially presents as night blindness (nyctalopia) slowly progressing to a considerable loss of peripheral visual field (tunnel vision) and finally to a complete absence of light perception. Cone function and central visual acuity are maintained until a late stage of the disease. A number of other ocular manifestations have been observed in Senior Loken syndrome including keratoconus, cataract, retinitis punctata albescens, and Coat's disease .
The diagnosis of Senior Loken syndrome is based on the clinical presentation of retinopathy and chronic interstitial nephritis. A complete workup of the organs involved is recommended, consisting of renal evaluation (urinalysis, renal function tests, abdominal ultrasound) and ophthalmologic tests (visual acuity, color vision, fundoscopy, refraction defects, ocular movements, electroretinogram). The liver should be assessed by liver function tests and ultrasound to exclude hepatic fibrosis. In addition, a neurological examination is recommended in infants.
On ultrasonography, the kidneys may show an increase in the echogenicity of renal parenchyma, cysts in a poorly differentiated corticomedullary junction or medullary cysts. These findings may eventually progress to more notable cysts and atrophy of the kidneys. A normal ultrasound appearance is possible in juvenile nephronophthisis but the diagnosis cannot be ruled out if medullary cysts are absent at the time of presentation .
Genetic analysis is required to diagnose Senior Loken syndrome. The most common mutation in this disease is the deletion of the gene NPHP1. Nephronophthisis can be diagnosed by mutational screening and histological findings on renal biopsy. Mutations in nine genes are linked to retinal degeneration and mutated NPHP1 to NPHP13 genes result in nephronophthisis.