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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