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Mervyn Thomas, Viral Sheth, Rebecca McLean, Frank Proudlock, Gail Maconachie, Susanne Kohl, Wai-Man Chan, Caroline Andrews, Elizabeth Engle, Irene Gottlob; Genotype-retinal phenotype correlations in infantile nystagmus. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4572.
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© ARVO (1962-2015); The Authors (2016-present)
Infantile nystagmus can arise as a result of mutations in genes expressed in the developing retina. Commonly mutated genes in infantile nystagmus include FRMD7, PAX6, CNGB3, CNGA3 and albinism associated genes. We aimed to compare the retinal phenotypes in these disorders using spectral domain optical coherence tomography (SD-OCT).
Sequencing was performed to identify FRMD7, PAX6, CNGB3 or CNGA3 mutations. Diagnosis of albinism was based on asymmetric visually evoked potentials and clinical features. SD-OCT (Copernicus HR) was used to image the fovea, parafovea and optic nerve head in patients with FRMD7 mutations (n=45), PAX6 mutations (n=14), albinism (n=34), achromatopsia (n=14) and controls (n=80).
Foveal hypoplasia was present in different proportions in the different groups (FRMD7=26%, PAX6 and albinism=100%, achromatopsia=71%). The foveal pit depth was significantly decreased in all groups (p<0.001), patients with albinism and PAX6 mutations were more severely affected in comparison to FRMD7 mutations and achromatopsia. The outer nuclear layer was significantly (p<0.001) thinner in the achromatopsia group. The outer segment length was significantly (p<0.001) decreased in all groups, the albinism group was most severely affected followed by PAX6 and FRMD7 groups. The achromatopsia group had disruption of this region. In the parafoveal regions all groups had a significantly decreased nerve fibre layer (NFL) thickness (p<0.001). A significant (p<0.001) reduction in GCL+IPL complex thickness and parafoveal retinal thickness were seen in all groups except the FRMD7 group. The peripapillary NFL thickness was significantly decreased (p<0.001) in all groups. The disc diameter was significantly decreased in all groups (p<0.001) except the albinism group. The cup depth was significantly decreased in all groups (p<0.001) except the achromatopsia group.
This is the first study comparing the retinal phenotypes associated with various mutations in infantile nystagmus. We identified varying severity based on the genotype. The phenotypes in CNGB3, CNGA3 and PAX6 mutations are consistent with findings in knockout mouse studies. Retinal phenotypes in patients with FRMD7 mutations are consistent with retinal expression studies. Taken together we highlight a spectrum of retinal changes which may suggest that improper sensorimotor integration could be the common aetiological factor in infantile nystagmus.
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