Approximately 10-15% of NPH patients show retinitis pigmentosa. The term Senior – Løken syndrome stands for the association of NPH with retinal degeneration. A distinction is made between two variants of retinal involvement:
1) Leber congenital amaurosis presents with blindness, nystagmus and nonreactive pupils in infancy. Typically children with congenital Leber amaurosis are rubbing or pressing their eyeballs in order to mechanically stimulate the retina and therewith produce visual effects.
2) The less severe variant is a tapetoretinal degeneration. Affected individuals present with slowly progressive restriction of the visual field and night blindness.
Funduscopy shows in both cases various degrees of retinal atrophy or pigmentary retinal alterations. The electroretinogram is severely flattened.
The occurrence of retinitis pigmentosa in patients with NPH depends on the underlying genetic mutation (6 – 13 % in NPHP1-3, 33% in NPHP4, 80 % in NPHP10, 100% in NPHP5, NPHP6 and IFT 140). Quite a few genes causing NPH are involved in the development of photoreceptors or influence their assembly.
Senior – Løken syndrome summary
| synonyms |
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| main symptoms |
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| additional findings |
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| manifestation | young children; blindness depends on underlying genetic mutation |
| frequency | ca. 1:1.000.000 |
| inheritance | autosomal – recessive |
| pathogenesis | Genes encode for proteins that localize on connecting cilia of retinal photoreceptors. Impaired function hampers the transport of rhodopsin and leads to the decay of photoreceptors. |
| progress and prognosis | Depending on the underlying mutation course of disease is highly variable. Visual impairment can be slowly progressive or congenital. Progressive chronic renal failure most often leads to end stage renal disease in adolescence. |
| treatment | No causal therapy available to date. A symptomatic treatment of chronic renal failure with renal replacement therapy and renal transplantation is necessary as well as a supportive therapy of visual impairment. |
Known SLSN genes to date
| Syndrome | Gene | Gene/Locus MIM number | |
| 1 | SLSN1 | NPHP1 | 607100 |
| 2 | SLSN3 | NPHP3 | 608002 |
| 3 | SLSN4 | NPHP4 | 607215 |
| 4 | SLSN5 | IQCB1/NPHP5 | 609237 |
| 5 | SLSN6 | CEP290/NPHP6 | 610142 |
| 6 | SLSN7 | SDCCAG8 | 613524 |
| 7 | SLSN8 | WDR19/IFT144 | 608151 |
| 8 | SLSN9 | TRAF3IP1 | 607380 |
(23.04.2018)
sources
- Ronquillo CC, Bernstein PS, Baehr W. Senior-Loken syndrome: a syndromic form of retinal dystrophy associated with nephronophthisis. Vision Res. 2012;75:88–97
- Wang J, Deretic D. Molecular complexes that direct rhodopsin transport to primary cilia. Prog Retin Eye Res. 2014;38:1–19.