Abstract
Background Variants in CRX are associated with dominantly inherited retinal degeneration with considerable phenotypic variability. Many patients have central retinal degeneration; in some patients, we have observed an additional focus of degeneration in the nasal retina. This study aims to describe this phenotypic association and estimate its prevalence amongst patients with CRX-associated disease.
Methods A retrospective review was conducted for all patients with CRX-associated retinal dystrophy at two UK centres. Analysis focused on patients with available ultra-widefield pseudocolour and autofluorescence imaging and aimed to identify those with a specific bifocal degeneration pattern involving the nasal retina in both eyes. International standard pattern and full-field ERGs were reviewed in the cohort with bifocal degeneration.
Results 60 patients with dominant CRX-associated retinal dystrophy were identified, with ultra-widefield fundus imaging available for 50 patients. Of these, six male patients aged 26–74 years displayed a distinct pattern of retinal degeneration, characterised by central retinal degeneration and an additional discrete area of abnormality in the nasal periphery (with altered autofluorescence characteristics), which was non-contiguous with the central macular degeneration. Electrophysiology indicated macular dysfunction in all 6 patients, with generalised cone (2 patients) or cone and rod (4 patients) system involvement, with a locus that was post-phototransduction and with the most severe case showing additional rod photoreceptor dysfunction. The CRX variants found in these patients included missense variants (2 patients), frameshifting variants (3 patients), and a CRX whole gene deletion (1 patient), with no clear genotype-phenotype correlation identified.
Conclusions We report a distinct pattern of bifocal retinal degeneration in some cases of CRX-associated retinal dystrophy (12% in our cohort), not typically seen in other forms of inherited retinal disease. Recognising such phenotypes can guide genetic investigations or their interpretation, facilitating molecular diagnoses for effective family counselling, given the autosomal dominant inheritance and phenotypic variability of CRX-associated retinopathy.
