Night Blindness, Congenital Stationary, CSNB1C

Clinical Characteristics
Ocular Features: 

Night blindness is a feature of many pigmentary and other retinal disorders, most of which are progressive.  However, there is also a group of genetically heterogeneous disorders, with generally stable scotopic defects and without RPE changes, known as congenital stationary night blindness (CSNB).  At least 10 mutant genes are responsible with phenotypes so similar that genotyping is usually necessary to distinguish them.  All are caused by defects in visual signal transduction within rod photoreceptors or in defective photoreceptor-to-bipolar cell signaling with common ERG findings of reduced or absent b-waves and generally normal a-waves.  The photopic ERG is usually abnormal to some degree as well and visual acuity may be subnormal.  In the pregenomic era, subtleties of ERG responses were frequently used in an attempt to distinguish different forms of CSNB.  Genotyping now enables classification with unprecedented precision.

Congenital stationary night blindness disorders are primarily rod dystrophies presenting early with symptoms of nightblindness and relative sparing of central vision.  Nystagmus and photophobia are usually not features.  Dyschromatopsia and loss of central acuity can develop later as the cones eventually become dysfunctional as well but these symptoms are much less severe than those seen in cone-rod dystrophies.  The amount of pigmentary retinopathy is highly variable. 

In this disorder (CSNB1C) the b-wave responses are severely deficient (no scotopic response) and a-waves seem to be normal.  Some reduction in central acuity is common.  High myopia may be present together with nystagmus and strabismus.  In one family, hypoplastic discs and relative thinning of the inner nuclear layer were described in twin brothers.  ERG responses suggest loss of ON bipolar cell function similar to that found in patients with GRM6 mutations (CSNB1B; 257270).

Systemic Features: 

No systemic disease is associated with congenital stationary night blindness.

Genetics

CSNB1C, or type 1C, is one of four congenital nightblindness disorders with autosomal recessive inheritance.  It results from mutations in the TRPM1 (15q13-q14) gene which encodes for a calcium ion channel protein, part of the GRM6 signaling cascade.  

Other autosomal recessive CSNB disorders are: CSNB2B (610427), CSNB (unclassified; OMIM number pending), and CSNB1B (257270).

Treatment
Treatment Options: 

No treatment beyond correction of the refractive error is available but tinted lenses are sometimes used to enhance vision.  Refractive errors need to be corrected and low vision aids can be helpful for those with some loss of central acuity.

References
Article Title: 

References

Miraldi Utz V, Pfeifer W, Longmuir SQ, Olson RJ, Wang K, Drack AV. Presentation of TRPM1-Associated Congenital Stationary Night Blindness in Children. JAMA Ophthalmol. 2018 Mar 8. doi: 10.1001/jamaophthalmol.2018.0185. [Epub ahead of print].

PubMedID: 29522070

Al Oreany AA, Al Hadlaq A, Schatz P. Congenital stationary night blindness with hypoplastic discs, negative electroretinogram and thinning of the inner nuclear layer. Graefes Arch Clin Exp Ophthalmol. 2016 Apr 15. [Epub ahead of print].

PubMedID: 27084085

Berger W, Kloeckener-Gruissem B, Neidhardt J. The molecular basis of human retinal and vitreoretinal diseases. Prog Retin Eye Res. 2010 Sep;29(5):335-75.

PubMedID: 20362068

Li Z, Sergouniotis PI, Michaelides M, Mackay DS, Wright GA, Devery S, Moore AT, Holder GE, Robson AG, Webster AR. Recessive mutations of the gene TRPM1 abrogate ON bipolar cell function and cause complete congenital stationary night blindness in humans. Am J Hum Genet. 2009 Nov;85(5):711-9.

PubMedID: 19878917

van Genderen MM, Bijveld MM, Claassen YB, Florijn RJ, Pearring JN, Meire FM, McCall MA, Riemslag FC, Gregg RG, Bergen AA, Kamermans M. Mutations in TRPM1 are a common cause of complete congenital stationary night blindness. Am J Hum Genet.2009 Nov;85(5):730-6.

PubMedID: 19896109