Definition: The Senior-Loken syndrome is the autosomal recessive association of nephronophthisis with retinitis pigmentosa or retinal aplasia consistent with Leber amaurosis.

Synopsis

 ocular anomalies

• retinitis pigmentosa
• retinal aplasia/retinal hypoplasia
• retinal dystrophy
• retinal degeneration

 cerebrospinal anomalies

• cerebellar ataxia
• censorineural hearing loss
• mental retardation (#11380932#)
• microcephaly (#11380932#)

 skeletal anomalies

• cone epiphyses

 congenital hepatic fibrosis

 renal anomalies

• medullary cystic kidneys
  • nephronophthisis
  • vasopressin-resistant diabetes insipidus

Etiology

SLSN1	2q13	-	NPHP1	MIM.256100
SLSN2
SLSN3	3q22	MIM.606995	NPHP3	MIM.604387
SLSN4	1p36	MIM.606966	NPHP4	MIM.607215
SLSN5	3q21.1	MIM.609254	IQCB1

Pathogenesis

 The renal-retinal syndrome Senior-Loken syndrome 1 (SLSN1), is caused by mutations in NPHP1-NPHP5. SLSN1 is characterized by the renal symptoms of NPHP and early-onset retinitis pigmentosa.

This phenotypic overlap can be explained by the fact that the primary cilium of renal epithelial cells is a structural equivalent to the connecting cilium of photoreceptor cells in the retina.

In the connecting cilia, cargo is trafficked along microtubule tracks from the photoreceptor inner segment to the outer segment through a motor protein complex that contains kinesin II, and back to the cell body through a cytoplasmic dynein. In this way, molecules of the visual pigment rhodopsin are transferred up and down the connecting cilia in every human retina each day.

An analogous intraciliary transport has been proposed for cilia of renal epithelial cells. Although nephrocystins might be part of the transported cargo, the exact composition of the cargo complex is unknown.

 The renal-retinal syndrome Senior-Loken syndrome 1 (SLSN1), which is caused by mutations in NPHP1-NPHP5, is characterized by the renal symptoms of NPHP and early-onset retinitis pigmentosa.

This phenotypic overlap can be explained by the fact that the primary cilium of renal epithelial cells is a structural equivalent to the connecting cilium of photoreceptor cells in the retina.

In the connecting cilia, cargo is trafficked along microtubule tracks from the photoreceptor inner segment to the outer segment through a motor protein complex that contains kinesin II, and back to the cell body through a cytoplasmic dynein.

In this way, 109 molecules of the visual pigment rhodopsin are transferred up and down the connecting cilia in every human retina each day. An analogous intraciliary transport has been proposed for cilia of renal epithelial cells. Although nephrocystins might be part of the transported cargo, the exact composition of the cargo complex is unknown.

References

 Hildebrandt F, Otto E. Cilia and centrosomes: a unifying pathogenic concept for cystic kidney disease? Nat Rev Genet. 2005 Dec;6(12):928-40. PMID: #16341073#