The Natural History of Inherited Retinal Dystrophy Due to Biallelic Mutations in the RPE65 Gene

Introduction: Mutations in the cone-rod homeobox ( CRX) gene, a known cause of inherited retinal dystrophy, are characterized by extensive phenotypic heterogeneity. We describe a novel presentation of rod-cone dystrophy (RCD) phenocopying pigmented paravenous retinochoroidal atrophy associated with a mutation in CRX. Case description: A 53-year-old man and his 48-year-old brother presented with a history of progressive vision loss and nyctalopia. Fundus examination revealed a bull’s eye lesion with chorioretinal atrophy and intraretinal pigment migration, while spectral-domain optical coherence tomography (SD-OCT) demonstrated retinal thinning with outer retinal atrophy. On short-wavelength autofluorescence (SW-AF) imaging, an atypical paravenous pattern of atrophy with a surrounding hyperautofluorescent border was observed. Full-field electroretinogram (ffERG) revealed a rod-cone pattern of dysfunction. A heterozygous pathogenic variant, c.119G>A:p.(Arg40Gln), in the CRX gene was identified in both brothers and segregated in their family. Conclusion: This case report broadens the currently known phenotypic presentations of CRX-associated retinopathy and suggests that mutations in CRX may be associated with pigmented paravenous retinochoroidal atrophy.

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Detailed clinical characterisation, unique features and natural history of autosomal recessive RDH12-associated retinal degeneration

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2018-313580 ◽

2019 ◽

pp. bjophthalmol-2018-313580 ◽

Cited By ~ 5

Author(s):

Abigail T Fahim ◽

Zaina Bouzia ◽

Kari H Branham ◽

Neruban Kumaran ◽

Mauricio E Vargas ◽

...

Keyword(s):

Natural History ◽

Retinal Degeneration ◽

Early Onset ◽

Vision Loss ◽

Age Of Onset ◽

Retinal Dystrophy ◽

Loss Of Function ◽

Phenotypic Data ◽

History Of ◽

Clinical Records

BackgroundDefects in retinol dehydrogenase 12 (RDH12) account for 3.4%–10.5 % of Leber congenital amaurosis and early-onset severe retinal dystrophy (EOSRD) and are a potential target for gene therapy. Clinical trials in inherited retinal diseases have unique challenges, and natural history studies are critical to successful trial design. The purpose of this study was to characterise the natural history of RDH12-associated retinal degeneration.MethodsA retrospective chart review was performed in individuals with retinal degeneration and two likely disease-causing variants in RDH12.Results57 subjects were enrolled from nine countries. 33 subjects had clinical records available from childhood. The data revealed an EOSRD, with average age of onset of 4.1 years. Macular atrophy was a universal clinical finding in all subjects, as young as 2 years of age. Scotopic and photopic electroretinography (ERG) responses were markedly reduced in all subjects, and a non-recordable ERG was documented as young as 1 year of age. Assessment of visual acuity, visual field and optical coherence tomography revealed severe loss of function and structure in the majority of subjects after the age of 10 years. Widefield imaging in 23 subjects revealed a unique, variegated watercolour-like pattern of atrophy in 13 subjects and sparing of the peripapillary area in 18 subjects.ConclusionsThis study includes the largest collection of phenotypic data from children with RDH12-associated EOSRD and provides a comprehensive description of the timeline of vision loss in this severe, early-onset condition. These findings will help identify patients with RDH12-associated retinal degeneration and will inform future design of therapeutic trials.

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How is the moral stance related to the intentional stance and group thinking?

Behavioral and Brain Sciences ◽

10.1017/s0140525x19002413 ◽

2020 ◽

Vol 43 ◽

Author(s):

Hannes Rakoczy

Keyword(s):

Natural History ◽

Social Cognitive ◽

Intentional Stance ◽

Cognitive Capacities ◽

Shared Intentionality ◽

History Of ◽

Group Thinking ◽

Moral Stance

Abstract The natural history of our moral stance told here in this commentary reveals the close nexus of morality and basic social-cognitive capacities. Big mysteries about morality thus transform into smaller and more manageable ones. Here, I raise questions regarding the conceptual, ontogenetic, and evolutionary relations of the moral stance to the intentional and group stances and to shared intentionality.

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