Abstract
Nephronophthisis (NPHP) is a childhood cystic kidney disease, which almost invariably
leads to end-stage renal disease in those affected. Recognition and diagnosis requires
clinical suspicion, biochemical evaluation, renal imaging and historically, renal
biopsy. Modern molecular genetics now allows a diagnosis to be made in a significant
proportion of cases. Mutations in NPHP1 account for 20% of cases, but the disease is genetically heterogeneous with at least
20 different genes associated with NPHP. Recent developments in the fields of genetics
and proteomics have led to increased understanding of the underlying pathogenetic
defects. Almost all NPHP genes encode proteins, which localize to the primary cilia,
basal body and centrosome. NPHP is a therefore considered to be a ciliopathy, and
can be part of a broad spectrum of clinical disease that includes extra-renal manifestations
including retinal degeneration, cerebellar ataxia, liver fibrosis and situs inversus.
In this review, we discuss the historical descriptions of NPHP in the context of more
recent developments in our understanding of this disease.
Keywords
Nephronophthisis - ciliopathy - cystic kidney disease - end-stage renal disease
