June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Chiasmal Misrouting in Infantile Nystagmus Syndrome(INS): Phenotypes in Patients with Molecular Diagnoses
Author Affiliations & Notes
  • Michael James Gilhooley
    Institute of Ophthalmology, University College London School of Life and Medical Sciences, London, England, United Kingdom
    Strabismus Department, Moorfields Eye Hospital NHS Foundation Trust, London, London, United Kingdom
  • Mariya Moosajee
    Institute of Ophthalmology, University College London School of Life and Medical Sciences, London, England, United Kingdom
    Department of Genetics, Moorfields Eye Hospital NHS Foundation Trust, London, London, United Kingdom
  • Magella M Neveu
    Department of Neurophysiology, Moorfields Eye Hospital NHS Foundation Trust, London, London, United Kingdom
  • Maria Theodorou
    Strabismus Department, Moorfields Eye Hospital NHS Foundation Trust, London, London, United Kingdom
  • Footnotes
    Commercial Relationships   Michael James Gilhooley None; Mariya Moosajee None; Magella Neveu None; Maria Theodorou None
  • Footnotes
    Support  MJG is supported by the National Institute of Health Research (NIHR) - Grant CL-2019-18-004, The Academy of Medical Sciences Grant SGL023\1051, Moorfields Eye Charity Grant GR001207 and Sight Research UK Grant SEE 006
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 5427. doi:
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      Michael James Gilhooley, Mariya Moosajee, Magella M Neveu, Maria Theodorou; Chiasmal Misrouting in Infantile Nystagmus Syndrome(INS): Phenotypes in Patients with Molecular Diagnoses. Invest. Ophthalmol. Vis. Sci. 2023;64(8):5427.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Chiasmal misrouting, once believed to be pathognomonic for albinism, has been reported in cases of INS, independent of melanin pathway disruption. The purpose of this study is to determine if there are clinical-electrophysiological parameters that correlate with particular genotypes in INS.

Methods : A retrospective chart review at Moorfields Eye Hospital identified 71 patients with a molecular diagnosis relating to INS. Visual acuity; presence of nystagmus, signs of albinism and OCT foveal hypoplasia grade were recorded alongside flash and pattern VEP (Visual Evoked Potential) amplitude and peak time. VEP asymmetry was assessed using the Pearson Correlation Coefficient (r).

Results : Pathological variants in 8 genes (TYR, OCA2, HPS6, HPS3, HPS1, GPR143, FRMD7, SLC38A8, OCA1) were identified. Mean BCVA per group ranged from 0.38-0.74LogMAR F(0.72,3.5)=2.8; p=0.04 one-way ANOVA. All genotypes demonstrated foveal hypoplasia (mode grade 4) except FRMD7 (all grade 1). In this cohort, positive flash and pattern VEP amplitude/peak time asymmetry correlated with clinical signs of albinism (flash VEP, r=0.22(0-6yrs); pattern VEP, r=0.17(6-65yrs)). There was marked asymmetry in SLC38A8 patients (r = -0.85 to-0.93), a feature known to be associated with foveal hypoplasia 2.

Conclusions : This study provides a detailed genotype-phenotype correlation of VEP findings in a molecularly characterised INS cohort - useful in selecting clinically guided genetic testing and counselling patients.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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