This renal-retinal phenotype seems to have an autosomal recessive pattern of inheritance but is genetically and clinically heterogeneous. Together these account for the majority of hereditary causes of end-stage renal disease in children and young adults. At least 5 renal-retinal disorders have been identified with a great deal of phenotypic overlap requiring genotyping for distinction. The common causative mechanism may be defects in the cilia of photoreceptors and renal epithelial cells.
SLNS1 (266900) is caused by mutations in the NPHP1 gene (2q12-13) encoding nephrocystin. Some form of pigmentary retinopathy is frequently present although its age of presentation is highly variable.
(There is a NPHP2 disorder [602088] but no SLSN disease is associated with the NPHP2 gene [now called INVS] at 9q22-31 and encoding inversin).
SLSN3 (606995) has been mapped to 3q21-22, overlapping the NPHP3 locus. This is a later onset, adolescent disease often presenting with anemia and renal failure occurring at a mean age of 19 years. 'Tapetoretinal degeneration' is part of the clinical picture.
SLSN4 (606996) is caused by mutations in the NPHP4 gene (encoding nephrocystin-3) and located at 1p36. The onset of retinal disease may be later in onset than in other conditions.
SLSN5 (IQCB1)(606254) is caused by mutations in the NPHP5 gene (encoding nephrocystin-5) and located at 3q13.33-21.2. Multiple mutations in this gene have been found and all patients have a pigmentary retinopathy.
SLSN6 (610189) results from mutations in the NPHP6 (CEP290) gene at 12q21. Some patients have had a 'tapetoretinal degeneration'.
SLSN7 (613615) is caused by mutations in the SDCCAG8 gene at 1q44. Some patients have retinal degeneration leading to blindness.
SLSN8 (616307) is caused by mutations in the WDR19 gene at 4p14. Patients have severe reduction in vision and visual fields are severely restricted. Bone spicule pigmentation can be seen in the periphery, the retinal vessels are attenuated, the ERG is undetectable, and there may be temporal pallor of the optic discs.
Hereditary disorders with isolated pigmentary retinopathy and cystic kidney disease also occur separately.
