As a group, Cone-Rod dystrophies occur at a prevalence of 1 out of 30,000 to 40,000 individuals.

CRD has genetically heterogeneous causes, with mutations in over 30 genes identified. It can be inherited in autosomal recessive, autosomal dominant or X-linked patterns (see RareShare Guide on Genetic Inheritance). Common genes involved include ABCA4, CERKL, CRX and GUCY2D.

Autosomal recessive inheritance, in which both parents are carriers, is the most common pattern, with mutations in the ABCA4 gene accounting for 30 to 60 percent of cases. At least 10 genes are associated with autosomal dominant cone-rod dystrophy. Mutations in the GUCY2D and CRX genes account for about half of such cases.

Decreased vision sharpness, peripheral vision, blind spots

Problems recognizing colors

Photophobia (light sensitivity)

Difficulty seeing in low light

Initial signs and symptoms typically include decreased visual acuity when looking straight ahead (central vision loss) and loss of color perception; and an abnormal sensitivity to light (photophobia). These signs are usually followed by progressive loss of peripheral vision and night blindness. This is followed by a wide-range of possible symptoms: abnormalities in the eyes/ears, intellectual disability, blindness, retinal flecks and central scotoma (https://rarediseases.info.nih.gov/gard/).

Diagnosis of CRD may involve a combination of evaluations and specialized tests:

1. Clinical examination including patient and family history to identify hereditary patterns, visual acuity and color vision testing, peripheral vision testing, and ophthalmoscopy to look for retinal degeneration.

2. Electroretinography (ERG) to measure electrical responses of retinal photoreceptor cells.

3. Optical Coherence Tomography (OCT) to look for structural changes associated with photoreceptor cell loss.

4. Genetic testing to look for mutations in specific genes associated with CRD.

Clinical diagnosis is based on the early decrease of visual acuity and photophobia, lesions in fundus, hypovolted ERG traces with predominant cone involvement, and progressive worsening of these signs. Full field ERG is the key test. At present, a systematic molecular testing is not routinely performed, due to the tremendous genetic heterogeneity of the disease. However, rapid and large-scale mutation screening techniques are developing and several laboratories perform search for mutations in the most frequently involved genes, including ABCA4, CRX, GUC1A; strategies to test in a short time several dozen of genes for a single patient DNA are emerging. Differential diagnoses are: Retinitis pigmentosa, Leber congenital amaurosis (LCA), Maculopathies ans Stationary retinal diseases (http://www.ncbi.nlm.nih.gov/pubmed).

Currently, CRD treatments focus on managing symptoms and slowing progression using the following:

1. Low vision aids such magnifying glasses, high contrast text and other assistive devices.

2. Protective eyewear such as sunglasses or tinted lenses to reduce light sensitivity and protect eyes from UV light.

3. Low vision rehabilitation programs to help patients maximize their remaining vision through adaptive techniques and devices.

4. Nutritional supplements with Vitamin A and Omega-3 fatty acids to seek to slow retinal degeneration.

Research is being conducted on the use of gene therapy and stem cell treatments for retinal diseases.

There are currently no specific therapies or treatments that can stop the progression of cone-rod dystrophy or restore vision, however there are ways to manage the disease. Light avoidance and low-vision aids may help to slow down the degenerative process (https://rarediseases.info.nih.gov/gard/). The beta-carotenoids, lutein and zeaxanthin, have been evidenced to reduce the risk of developing age related macular degeneration (AMD). Consuming omega-3 fatty acids (docosahexaenoic acid and eicosapentaenoic acid) has been correlated with a reduced progression of early AMD, and in conjunction with low glycemic index foods, with reduced progression of advanced AMD (https://en.wikipedia.org/wiki/Main_Page). Finally, it is also important for patients to receive support to help them cope with the social and psychological impact of vision loss (https://rarediseases.info.nih.gov/gard/).

There is currently no cure for CRD. The disease may appear in childhood and worsen over time, potentially leading to blindness. Management through support from low vision specialists can help patients cope with the condition and try to slow disease progression.

Medline Plus, Cone-rod dystrophy:  https://medlineplus.gov/genetics/condition/cone-rod-dystrophy/#references.

Hamel CP. Cone rod dystrophies. Orphanet J Rare Dis. 2007 Feb 1;2:7. doi: 10.1186/1750-1172-2-7:  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1808442/?_ga=2.72143381.783164365.1719850935-382328039.1719267011.