Multimodal Imaging in Autosomal Dominant Cone-Rod Dystrophy Caused by Novel <b><i>CRX</i></b> Variant

Abstract

Aim: To characterize by multimodal approach the phenotype of patients from a 3 generations pedigree, affected by autosomal dominant cone-rod dystrophy (CRD), found to carry a novel pathogenic variant in the cone-rod homeobox-containing (CRX) gene. Methods: Examination of the adult patients included the following tests: visual acuity, multicolour imaging, spectral domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF) and OCT angiography (OCT-A) recordings. In a 2.5-year-old child, cycloplegic refraction, fundoscopy, ocular motility evaluation and electrophysiological exams were performed. Next Generation Sequencing of patients’ DNA has been carried out. Results: A novel CRX pathogenic variant has been identified in our patients. The 2.5-year-old child in the third generation was found to have inherited the variant, with no clinical signs of the condition, but electroretinographic abnormalities in the scotopic component. In the adult patients, diffuse atrophy of the retinal pigment epithelium/photoreceptor complex in the macular region was evident at the OCT and FAF, while OCT-A showed choriocapillaris density reduction. Conclusions: Multimodal study allowed the characterization of a peculiar form of CRD. The novel pathogenic variant seems to have a different effect on the phenotype if compared with a previously described similar one, giving an insight into the pathogenic mechanism of CRX-related retinal dystrophies and offering valuable information that could lead to the development of possible future therapies.

Occult Macular Dysfunction Syndrome: Identification of Multiple Pathologies in a Clinical Spectrum of Macular Dysfunction with Normal Fundus in East Asian Patients: EAOMD Report No. 5

“…CRX, a cone-rod homeobox-containing gene (OMIM: 602225), encodes a homeodomain transcription factor crucial for the development and survival of photoreceptors [85,86]. CRX-retinopathy encompasses severe AR-LCA, AR-RP, AD-CORD, AD-COD, and AD-MD; AD-MD shows a mild phenotype [39,[87][88][89][90][91][92][93][94][95][96][97][98][99][100][101]. The relatively mild phenotype of patients with CRX-OMD is consistent with the previous AD-CRX cases [87], although there are no reported CRX cases with the identical variant.…”

How to Set Up Genetic Counselling for Inherited Macular Dystrophies: Focus on Genetic Characterization

“…In the complex scenario of IRDs, some genes display a marked phenotypic heterogeneity, potentially causing either distinct macular dystrophies or diffused diseases. In particular, this is the case for genes PROM1, IMPG1, FSCN2, OTX2, CRX, RAB28, and GUCA1A [26,27].…”

Reviewing the Role of Ultra-Widefield Imaging in Inherited Retinal Dystrophies

“…Patients with primary cone degeneration and secondary rod disruption may also develop retinal vascular attenuation and peripheral pigment deposits, mimicking RP. FAF, OCT, and OCTA macular abnormalities have been extensively described in patients with CD, CRD, and localized cone [66][67][68][69]. On the other hand, reports on UWF changes in these patients are still scarce.…”