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Congenital stationary night blindness: for professionals


Overview

PrevalenceEstimated at 1 in 70,000 live births
InheritanceX-linked, autosomal recessive, or autosomal dominant depending on the subtype
Genes Involved (OMIM No.)Riggs Type CSNB: RHO (OMIM: #180380), GNAT1 (OMIM: #139330), PDE6B (OMIM: #180072), SLC24A1 (OMIM: #603617), CNGB1 (OMIM: #600724).
Schubert-Bornschein Type CSNB: NYX (OMIM: #300278), TRPM1 (OMIM: #603576), GRM6 (OMIM: #604096), GPR179 (OMIM: #614515), LRIT3 (OMIM: #615004).
Fundus Albipunctatus: RDH5 (OMIM: #601617).
Oguchi Disease: SAG (OMIM: #181031), GRK1 (OMIM: #180381).
SymptomsNyctalopia Double vision Reduced visual acuity Photophobia (incomplete CSNB) Colour vision impairment (incomplete CSNB)
Ocular FeaturesNormal fundus Nystagmus High myopia or hypermetropia Strabismus
Key InvestigationsOphthalmic Fundoscopy Optical Coherence Tomography (OCT) Fundus Autofluorescence (FAF) Electroretinogram (ERG) Visual Field Testing Colour Vision Testing
Molecular DiagnosisWhole genome sequencing with retinal panel
ManagementOcular: Regular ophthalmic monitoring to assess visual development and manage refractive errors Correction of high myopia or hypermetropia with glasses or contact lenses Amblyopia management if strabismus is present Use of low vision aids as needed
Systemic: Genetic counselling for affected individuals and their families Supportive therapies for any associated conditions if part of a syndromic presentation
Therapies under ResearchOngoing animal studies on gene therapies

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Clinical phenotype

Congenital stationary night blindness (CSNB) is a group of genetically determined, largely non-progressive retinal disorders characterised by rod system dysfunction. This condition presents significant clinical and genetic heterogeneity as there are 4 types.1,2 Diagnosis relies on full-field electroretinograms (ERG) and genetic testing to differentiate between subtypes.

Presenting features

Ocular

  1. Riggs Type CSNB
    • Night Blindness: Primary symptom, often presenting in childhood.3
    • Visual Acuity: Typically preserved but may decline in some cases.
    • Fundus Appearance: Normal.
    • Additional Symptoms: Myopia, strabismus, nystagmus (pendular, dysconjugate, oblique, high frequency, low amplitude).
  2. Schubert-Bornschein Type CSNB
    • Night Blindness: Present from early childhood.4
    • Visual Acuity: Mild to moderate reduction.
    • Fundus Appearance: Normal.
    • Additional Symptoms: Myopia, strabismus, nystagmus (similar characteristics as Riggs type).
    • Subtypes:
      • Complete: More severe nyctalopia and reduced visual acuity, often with photophobia.
      • Incomplete: Variable symptoms, often less severe than complete subtype.
  3. Fundus Albipunctatus
    • Night Blindness: Present from early childhood.5
    • Visual Acuity: Usually preserved.
    • Fundus Appearance: Small white dots scattered across the posterior pole sparing the fovea.
    • Additional Symptoms: Myopia, strabismus, nystagmus (as described for Riggs type).
  4. Oguchi Disease
    • Night Blindness: Present from early childhood.6,7
    • Visual Acuity: Typically preserved.
    • Fundus Appearance: Gray-white metallic sheen that disappears after dark adaptation (Mizuo-Nakamura phenomenon).
    • Additional Symptoms: Myopia, strabismus, nystagmus (as described for Riggs type)8

Systemic

  • No systemic features are typically associated with CSNB, making it primarily an ocular condition.

Genetics

  1. Riggs Type CSNB
    • Genes: RHO (OMIM: #180380), GNAT1 (OMIM: #139330), PDE6B (OMIM: #180072), SLC24A1 (OMIM: #603617), CNGB1 (OMIM: #600724).1,9
    • Inheritance Pattern: Autosomal dominant or recessive.
    • Effect: Defects in rod phototransduction cascade.
  2. Schubert-Bornschein Type CSNB
    • Genes: NYX (OMIM: #300278), TRPM1 (OMIM: #603576), GRM6 (OMIM: #604096), GPR179 (OMIM: #614515), LRIT3 (OMIM: #615004).1,10,11,12
    • Inheritance Pattern: Autosomal recessive (except NYX which is X-linked).
    • Effect: Defects in ON- and/or OFF-bipolar cell pathways.
  3. Fundus Albipunctatus
    • Gene: RDH5 (OMIM: #601617).1
    • Inheritance Pattern: Autosomal recessive.
    • Effect: Defects in 11-cis-retinol dehydrogenase, leading to delayed dark adaptation.
  4. Oguchi Disease
    • Genes: SAG (OMIM: #181031), GRK1 (OMIM: #180381).1,7
    • Inheritance Pattern: Autosomal recessive.
    • Effect: Defects in rod phototransduction, resulting in prolonged recovery of rod function after light exposure.

Further information about each gene can be found on OMIM and Medline Plus.

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Key investigations

Ocular

  1. Fundus examination: Typically normal apart from myopic changes.
  2. Optical Coherence Tomography (OCT): Usually normal; no specific findings unique to CSNB.
  3. Electrophysiological testing13-17
    • Riggs Type CSNB
      • Dark-Adapted Dim Flash (DA 0.01) ERG: Non-detectable.
      • Dark-Adapted Strong Flash (DA 3.0) ERG: Reduced a- and b-waves.
      • Light-Adapted 3.0 ERG (single-flash cone response): Normal.
      • Light-Adapted 3.0 ERG (30 Hz flicker): Normal.
    • Schubert-Bornschein Type CSNB
      • Dark-Adapted Dim Flash (DA 0.01) ERG: Non-detectable.
      • Dark-Adapted Strong Flash (DA 3.0) ERG: Normal a-wave, severely reduced b-wave (electronegative waveform).
      • Light-Adapted 3.0 ERG (single-flash cone response):
        • Complete subtype: Preserved a-wave, widened trough with sharply rising b-wave.
        • Incomplete subtype: Reduced a- and b-waves with a markedly reduced b ratio.
      • Light-Adapted 3.0 ERG (30 Hz flicker):
        • Complete subtype: Flattened trough with or without a mild implicit time shift.
        • Incomplete subtype: Reduced amplitude and distinctive bifid waveforms.
    • Fundus Albipunctatus
      • ERG: Delayed recovery of rod function after light exposure, showing prolonged dark adaptation.
    • Oguchi Disease
      • ERG: Similar to fundus albipunctatus, with delayed recovery of rod function after light exposure, characteristic of the Mizuo-Nakamura phenomenon.
  4. Visual Field Testing: Can show central or peripheral field defects.
  5. Genetic Testing: Targeted gene panel testing or whole exome sequencing to identify causative mutations.

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Diagnosis

Diagnosis is confirmed through clinical evaluation, ERG findings, and genetic testing. Differentiating between complete and incomplete CSNB is crucial for accurate diagnosis and management.

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Differential Diagnoses

Conditions with similar ocular features include:

  • Retinitis pigmentosa (RP)
  • Leber congenital amaurosis (LCA)
  • Achromatopsia
  • X-linked retinoschisis (XLRS)

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Management

MIDD requires a comprehensive and multidisciplinary management approach.

Ocular

  1. Regular ophthalmic monitoring
    • Routine eye exams to monitor visual acuity and refractive errors.1
  2. Refractive correction
    • Glasses or contact lenses to correct myopia or hypermetropia.
  3. Amblyopia treatment
    • Particularly in cases with associated strabismus.
  4. Low vision aids
    • To assist patients with significant visual impairment.

Family management and counselling

Patients and families require genetic counselling and can seek advice for family planning including prenatal testing and preimplantation genetic diagnosis.

Emotional and social support

Genetic counsellors and Eye Clinic Liaison Officers (ECLOs) act as an initial point of contact for newly diagnosed patients and their parents in clinic. They provide emotional and practical support to help patients and parents deal with the diagnosis and maintain independence. They work closely with the local council’s sensory support team and are able to advise on the broad range of services provided, such as visual rehabilitation, home assessment, work and access to qualified teachers for children with visual impairment (QTVI) among other services.

Related links

Referral to a specialist centre

In the UK, patients should be referred to their local genomic ophthalmology (if available) or clinical genetics services to receive a more comprehensive genetic management of their conditions (genetic testing and genetic counselling) and having the opportunity to participate in clinical research

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Current research

Research endeavours in CSNB focus on gene therapies, aiming to correct the genetic mutations responsible for the condition. Whilst there are no current human trials for this previous work with gene therapy on mouse models have been promising.18,19

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Further information and support

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References

  1. Kim AH, Liu PK, Chang YH, et al. Congenital Stationary Night Blindness: Clinical and Genetic Features. Int J Mol Sci. 2022;23(23):14965. doi: 10.3390/ijms232314965. PMID: 36499293; PMCID: PMC9740538.
  2. Tsang SH, Sharma T. Congenital Stationary Night Blindness. Adv Exp Med Biol. 2018;1085:61-64. doi: 10.1007/978-3-319-95046-4_13.
  3. Liu X., Zhuang S., Hu S., Zhang F., Lin B., Li X., Xu D., Chen S.H. A dominant form of congenital stationary night blindness (adCSNB) in a large Chinese family. Ann. Hum. Genet. 2005;69:315–321. doi: 10.1046/J.1469-1809.2005.00159.x.
  4. Sergouniotis PI, Robson AG, Li Z, et al. A phenotypic study of congenital stationary night blindness (CSNB) associated with mutations in the GRM6 gene. Acta Ophthalmol. 2011;90. doi: 10.1111/j.1755-3768.2011.02267.x.
  5. Baldwin, A. N., Robson, A. G., Moore, A. T., & Duncan, J. L. (2018). Ryans retina (pp. 1006-1017) (A. P. Schachat, Ed.). Edinburgh: Elsevier.
  6. Pieh C, Simonsz-Toth B, Gottlob I. Nystagmus characteristics in congenital stationary night blindness (CSNB). Br J Ophthalmol. 2008;92:236-240. doi: 10.1136/bjo.2007.126342.
  7. Rishi P, Rishi E, Abraham S. Oguchi’s disease with Mizuo-Nakamura phenomenon in a seven-year-old boy. GMS Ophthalmol Cases. 2018 Dec 13;8:Doc07. doi: 10.3205/oc000089. PMID: 30607313; PMCID: PMC6308901.
  8. Papageorgiou E, McLean RJ, Gottlob I. Nystagmus in childhood. Pediatr Neonatol. 2014;55:341-351. doi: 10.1016/j.pedneo.2014.02.007.
  9. Bijveld MM, Florijn RJ, Bergen AA, et al. Genotype and phenotype of 101 Dutch patients with congenital stationary night blindness. Ophthalmology. 2013;120:2072-2081. doi: 10.1016/j.ophtha.2013.03.002.
  10. Zeitz C, Robson AG, Audo I. Congenital stationary night blindness: An analysis and update of genotype-phenotype correlations and pathogenic mechanisms. Prog Retin Eye Res. 2015;45:58-110. doi: 10.1016/j.preteyeres.2014.09.001.
  11. Sergouniotis PI, Robson AG, Li Z, et al. A phenotypic study of congenital stationary night blindness (CSNB) associated with mutations in the GRM6 gene. Acta Ophthalmol. 2012;90. doi: 10.1111/j.1755-3768.2011.02267.x.
  12. Wang Q, Gao Y, Li S, Guo X, Zhang Q. Mutation screening of TRPM1, GRM6, NYX and CACNA1F genes in patients with congenital stationary night blindness. Int J Mol Med. 2012;30:521-526. doi: 10.3892/ijmm.2012.1039.
  13. McCulloch DL, Marmor MF, Brigell MG, et al. ISCEV Standard for full-field clinical electroretinography (2015 update). Doc Ophthalmol. 2015;130:1-12. doi: 10.1007/s10633-014-9473-7.
  14. Marmor MF, Zeitz C. Riggs-type dominant congenital stationary night blindness: ERG findings, a new GNAT1 mutation and a systemic association. Doc Ophthalmol. 2018;137:57-62. doi: 10.1007/s10633-018-9651-0.
  15. Kabanarou SA, Holder GE, Fitzke FW, Bird AC, Webster AR. Congenital stationary night blindness and a “Schubert-Bornschein” type electrophysiology in a family with dominant inheritance. Br J Ophthalmol. 2004;88:1018-1022. doi: 10.1136/bjo.2003.033555.
  16. Miyake Y, Yagasaki K, Horiguchi M, Kawase Y. On- and off-responses in photopic electroretinogram in complete and incomplete types of congenital stationary night blindness. Jpn J Ophthalmol. 1987;31:81-87.
  17. Hasan N, Pangeni G, Cobb CA, et al. Presynaptic Expression of LRIT3 Transsynaptically Organizes the Postsynaptic Glutamate Signaling Complex Containing TRPM1. Cell Rep. 2019;27:3107-3116.e3. doi: 10.1016/j.celrep.2019.05.056.
  18. Scalabrino ML, Boye SL, Fransen KM, et al. Intravitreal delivery of a novel AAV vector targets ON bipolar cells and restores visual function in a mouse model of complete congenital stationary night blindness. Hum Mol Genet. 2015;24:6229-6239. doi: 10.1093/hmg/ddv341.

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Updated on June 3, 2024
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