Nephronophthisis-medullary cystic disease: clinical and genetic aspects

Nephronophthisis (NPH)/medullary cystic disease (MCD) is an intriguing complex. NPH and MCD have been considered in the past to be the same entity, being histologically indistinguishable and showing a similar clinical behavior. In both entities, clinical onset and course are so insidious, and involve such a paucity of signs and symptoms, that diagnosis in the pre-azotemic stage is very uncommon. Extrarenal manifestations are often associated only to NPH. Nevertheless the two forms can be distinguished on the basis of inheritance and evolution. Indeed, in NPH, end-stage renal failure is encountered during early adolescence, while it occurs late in adulthood in MCD; more importantly, however, the mode of inheritance differs, being autosomal recessive in NPH and autosomal dominant in MCD. Since the beginning of the 1990s, studies on molecular genetics have led to the identification of a candidate gene for NPH on chromosome 2: in 60-70% of the NPH population a large homozygous deletion has been found. In NPH-associated retinal lesions (Senior Loken syndrome), no linkage with chromosome 2 gene loci have been identified. Studies on MCD-affected families have so far excluded an MCD gene on chromosome 2.