Nephronophthisis (NPHP) is an autosomal recessively inherited renal disorder, which leads to progressive renal failure, usually within the first 3 decades of life.1
Nephronophthisis literally means ‘disappearance of nephrons'. Typical ultrasound features include normal or reduced renal size, loss of corticomedullary differentiation and corticomedullary cysts (). Renal biopsy findings include tubular atrophy, interstitial fibrosis and tubular basement membrane defects, including abrupt transition between thickening and attenuation or disintegration.2, 3
A rare form of NPHP may lead to end-stage renal failure (ESRF) within 5 years of age and is termed infantile NPHP.4
This differs from typical NPHP in that there is moderate renal enlargement, histological changes that include cortical microcysts, cystic dilatation of Bowman's spaces and lack of tubular basement membrane disruption.
Ultrasound scan features of nephronophthisis. Renal ultrasound scan demonstrating corticomedullary cysts, some of which are arrowed.
NPHP is often part of a spectrum of multisystem disease and may not be detected unless appropriate investigations on relevant systems are performed. These disease associations form a very heterogeneous group (). The most commonly associated syndrome is retinal dystrophy and retinal degeneration leading to blindness (Senior–Loken syndrome).1
Other associations include Joubert syndrome and related diseases (JSRD, reviewed in reference5
), which often involves a cerebellar, retinal and renal phenotype referred to as CORS (cerebello-oculo-renal syndrome). Apart from these, a whole variety of syndromes have been reported in association with NPHP ().
Syndromes which may exhibit nephronophthisis or are associated with mutations in NPHP genes
NPHP has been reported worldwide, yet the incidence varies. A Canadian study reported an incidence of 1 in 50
000 live births,6
whereas the incidence in the United States of America was estimated to be 9 per 8.3 million.7
A more recent European study reported an incidence of NPHP as 1 in 61
800 live births.8
However, as NPHP may present in adults with late enuresis and renal failure,9
these figures may be an underestimate.