Cone–rod dystrophy

Cone-rod dystrophy is characterised by progressive impairment of central and colour vision. Onset typically occurs in childhood or early adulthood, with reduced visual acuity, colour-vision abnormalities and photophobia; nystagmus may also occur. Fundus examination commonly reveals a bull’s-eye maculopathy, although findings may initially be limited to subtle macular atrophy or pigmentary changes. Optic-disc pallor may develop during the course of the disease.

Cone dysfunction predominates initially, whereas subsequent rod involvement distinguishes cone-rod dystrophy from isolated cone dystrophy. Rod involvement is associated with impaired dim-light vision and progressive constriction of the peripheral visual field. In advanced disease, both cone and rod function may be severely impaired, making clinical differentiation from rod-cone dystrophy difficult. Full-field electroretinography permits separate assessment of generalised cone- and rod-mediated retinal function and helps distinguish the two patterns, particularly earlier in the disease course.

Because central vision is affected early, cone-rod dystrophy may lead to substantial visual impairment from an early stage, although the severity and progression vary according to the underlying genetic cause. Cone-rod dystrophy is non-syndromic in many affected individuals but may also occur as part of a syndromic condition.

The estimated prevalence of cone and cone-rod dystrophy is 1/40,000.

Cone-rod dystrophy is genetically heterogeneous, with autosomal recessive, autosomal dominant and X-linked forms. ABCA4 is an important cause of recessive disease, while GUCY2D and RPGR are representative of dominant and X-linked forms, respectively. The genotype-phenotype relationship is variable, and variants in these and other genes may be associated with a broader spectrum of inherited retinal dystrophies.

The genetic conditions associated with cone-rod dystrophy follow heterogeneous inheritance patterns. Autosomal recessive, autosomal dominant and X-linked inheritance have all been documented, with autosomal recessive inheritance being the most common and X-linked inheritance being rare.

• Molecular genetic testing can establish the underlying genetic diagnosis, confirm the clinical suspicion, enable predictive testing of at-risk family members and provide information relevant to family planning.
• The identified entity supports condition-specific monitoring and management decisions; therapeutic options are evaluated individually by the treating physicians.

• Haraguchi Y, Chiang TK, Yu M. Application of electrophysiology in non-macular inherited retinal dystrophies. J Clin Med. 2023;12(21):6953. doi:10.3390/jcm12216953. PMID:; PMCID:PMC10649281.
• AV, Sheplock R, Sumaroka A, Roman AJ, Cideciyan AV, Jacobson SG. Childhood-onset genetic cone-rod photoreceptor diseases and underlying pathobiology. EBioMedicine. 2021;63:103200. doi:10.1016/j.ebiom.2020.103200. PMID:; PMCID:PMC7806809.
• Boulanger-Scemama E, El Shamieh S, Démontant V, Condroyer C, Antonio A, Michiels C, et al. Next-generation sequencing applied to a large French cone and cone-rod dystrophy cohort: mutation spectrum and new genotype-phenotype correlation. Orphanet J Rare Dis. 2015;10:85. doi:10.1186/s13023-015-0300 PMID:; PMCID:PMC4566196.