Autosomal dominant cone-rod dystrophy caused by a mutation in the cone-rod homeobox (CRX) gene
A patient presented with decreased vision, photophobia and glare affecting both eyes within the past year. Their past medical history included sleep apnea and anxiety/depression treated with hydroxyzine and sertraline. They denied autoimmune disease, cancer, and the use of other high-risk medications. One parent had been diagnosed with Stargardt disease; however, no other family members were affected. BCVA was 20/30 OD and 20/40 OS with low myopic correction. Intraocular pressures and anterior segment examination were within normal limits. On dilated fundus examination, symmetric findings were noted in both eyes, including RPE mottling of the central maculae and islands of RPE mottling nasal to the optic nerve. These areas appeared hypo-autofluorescent centrally with a hyper- autofluorescent ring on fundus autofluorescence. SD-OCT demonstrated outer retinal thinning with atrophy of the IS/OS parafoveally. Given their family history, an inherited retinal disease was suspected, and genetic testing was performed through Invitae, which revealed a pathogenic mutation in the cone-rod homeobox (CRX) gene (c.449C > G / p.S150*). Mutations in CRX, a transcription factor involved in photoreceptor development, typically cause autosomal dominant disease and can lead to multiple phenotypes, including cone-rod dystrophy, macular dystrophy, retinitis pigmentosa, and Leber congenital amaurosis. Mutations in CRX are enriched in the DNA-binding and transactivating domains of the transcription factor and elicit dominant negative and gain-of-function effects common among autosomal dominant disorders. The phenotype of this patient appeared most consistent with an autosomal dominant cone-rod or macular dystrophy. Currently, there are limited therapeutic options for patients with CRX mutations. Management moving forward includes complete clinical phenotypic characterization and monitoring, pairing with clinical trials/new therapies as they arise, participation in a low vision clinic when appropriate, and referral for genetic counseling and family planning.
Presentation Date: 08/29/2024
Issue Date: 09/11/2024
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