CNGB3-Related Congenital Color Vision Deficiency (Achromatopsia Type 3)

Gene and Genomic Region

CNGB3

Achromatopsia type 3 is caused by mutations in both copies of the CNGB3 gene, which are inherited in an autosomal recessive pattern. This means that a child must inherit one defective copy of the gene from each parent to develop the condition, while carriers with only one mutated copy usually do not experience symptoms.

The CNGB3 gene is located on chromosome 8 at position q21.3. It encodes a protein that is critical for forming the beta-subunit of a channel in cone photoreceptor cells. This channel is essential for converting light into electrical signals that are sent to the brain. When mutations occur, the channel is disrupted, preventing cone cells from functioning normally and leaving vision reliant almost entirely on rod cells, which handle low-light vision but do not detect color.

Names and Synonyms

Achromatopsia is sometimes called “congenital color blindness” or “complete color blindness,” terms that reflect the absence of functional color vision from birth. When CNGB3 mutations are the underlying cause, the condition is referred to as Achromatopsia type 3, or ACHM3.Other terms have emerged over time. The condition is sometimes known as rod monochromacy, because individuals retain rod function while cone function is absent. It is also known as Pingelapese blindness in certain regions, notably Pingelap Island in Micronesia, where a specific CNGB3 mutation is unusually prevalent due to a genetic bottleneck event in the island’s history.

Overview of the Condition

How It Affects the Eye

In CNGB3-related achromatopsia, the cone photoreceptors in the retina are structurally present but do not function properly. Because cones are responsible for handling daylight and color information, their absence forces individuals to rely primarily on their rod cells. This imbalance leads to discomfort in bright environments, diminished visual acuity, and a complete inability to distinguish colors.

Core Symptoms

The most prominent symptom is photophobia, or light sensitivity, which makes it difficult to function in bright conditions. Many individuals also experience nystagmus, characterized by involuntary, rapid movements of the eyes that can make focusing difficult. Visual sharpness is typically reduced; in complete cases, vision measures around 0.1 or less, roughly equivalent to 20/200 in clinical testing.

Color perception is absent, meaning individuals perceive their environment in shades of gray. In some cases, central scotomas, or small blind spots in the center of the visual field, develop, forcing the person to rely on eccentric fixation for clearer vision. Refractive errors, such as nearsightedness, farsightedness, or astigmatism, are also common, although they can often be corrected with lenses.

The course of the condition is typically stable. However, some patients show gradual changes over time, including slight deterioration in visual acuity or subtle structural changes in the retina detectable on imaging.

Epidemiology

Achromatopsia is considered a rare genetic disorder, occurring in approximately one in 30,000 to one in 50,000 people worldwide. Among all cases of achromatopsia, CNGB3-related variants are the most common, representing approximately 60 to 70 percent of diagnosed cases. The c.1148delC mutation is particularly notable, as it accounts for about 40 percent of all cases globally and is especially frequent in populations of European ancestry. This concentration reflects historical founder effects and genetic drift in certain populations.

Etiology

Genetic Mechanism

The CNGB3 gene produces a critical beta-subunit of a cyclic nucleotide-gated ion channel in cone cells. This channel allows the phototransduction cascade—the process by which light is converted into electrical signals—to occur effectively. When mutations disrupt this protein, cone cells cannot generate proper responses to light, leading to severely impaired visual function in bright light and complete loss of color discrimination.

Symptoms

Early Presentation

The first signs of the disorder usually appear in infancy. Parents often notice that their child is extremely sensitive to light or has unusual eye movements within the first few weeks or months of life.

Clinical Features

Children and adults with achromatopsia type 3 typically experience intense discomfort in bright environments, difficulty focusing due to nystagmus, and markedly reduced visual acuity. The inability to perceive any colors is a defining feature of the condition. Over time, some individuals may develop central blind spots or rely on off-center fixation to see more clearly. Refractive errors are frequent and can compound visual challenges but are generally manageable with corrective lenses.

Although the disease is often described as stable, recent longitudinal studies suggest that a subset of patients may experience slow, progressive changes in visual function or retinal structure as they age.

Testing & Diagnosis

Accurate diagnosis relies on a combination of clinical evaluation, imaging, functional testing, and genetic analysis. Ophthalmologists begin with a clinical examination to assess common indicators such as photophobia, nystagmus, and reduced visual acuity, which are often evident during infancy.

Color vision testing, using methods such as the Farnsworth D-15 or an anomaloscope, helps quantify the degree of color perception loss. Electroretinography (ERG) provides functional confirmation, typically showing severely reduced or absent cone responses, while rod responses remain intact. Imaging techniques like optical coherence tomography (OCT) provide high-resolution views of the retina, often revealing underdeveloped or structurally altered cones in the macula. Fundus autofluorescence (FAF) may also reveal areas of metabolic stress or early signs of retinal damage.

Genetic testing serves as the definitive diagnostic step, allowing clinicians to confirm the presence of mutations in both copies of the CNGB3 gene and to provide accurate counseling for families.

Treatment & Management

At present, there is no cure for CNGB3-related achromatopsia, but several strategies can help manage symptoms and improve quality of life. Tinted or light-filtering lenses are commonly prescribed to reduce light sensitivity, while magnifiers and electronic visual aids can help compensate for reduced acuity. For children, educational support, such as preferential seating in classrooms and access to enlarged or high-contrast materials, is often recommended to facilitate learning

Emerging and Experimental Therapies

CNGB3-related achromatopsia has long been considered a stable, non-progressive condition, but evidence from recent studies indicates that some individuals may experience a slow decline in visual function or gradual structural changes in the retina over time. Early diagnosis and ongoing monitoring are important, as they allow patients to take advantage of emerging therapies, which may be most effective when started during early developmental stages.

Helpful Terms

A gene is a segment of DNA that carries the instructions for producing proteins, which direct the body’s growth, development, and function.
Autosomal recessive inheritance refers to a genetic pattern in which two copies of a faulty gene, one inherited from each parent, are necessary for the condition to manifest.
The CNGB3 gene encodes a protein essential for cone photoreceptor function, making it critical for color vision.
Achromatopsia describes a spectrum of disorders in which cone cells are nonfunctional, leading to complete color blindness and significant visual impairment.
Gene therapy is an emerging medical approach aimed at replacing or repairing defective genes to restore normal cellular function.

References

• Pascual-Camps, Isabel, et al. ‘Diagnosis and Treatment Options for Achromatopsia: A Review of the Literature’. Journal of Pediatric Ophthalmology & Strabismus, vol. 55, no. 2, Mar. 2018, pp. 85–92. DOI.org (Crossref), https://doi.org/10.3928/01913913-20171117-01.
• Kohl, Susanne, and Christian P. Hamel. ‘Clinical Utility Gene Card for: Achromatopsia’. European Journal of Human Genetics, vol. 19, no. 6, Jun. 2011, pp. 732–732. DOI.org (Crossref), https://doi.org/10.1038/ejhg.2010.231.
• Andersen, Mette Kjøbæk Gundestrup, et al. ‘Genetic and Clinical Characterization of Danish Achromatopsia Patients’. Genes, vol. 14, no. 3, Mar. 2023, p. 690. DOI.org (Crossref), https://doi.org/10.3390/genes14030690.
• Brunetti-Pierri, Raffaella, et al. ‘Clinical and Molecular Characterization of Achromatopsia Patients: A Longitudinal Study’. International Journal of Molecular Sciences, vol. 22, no. 4, Feb. 2021, p. 1681. DOI.org (Crossref), https://doi.org/10.3390/ijms22041681.
• Andersen, Mette Kjøbæk Gundestrup, and Line Kessel. ‘Ametropia and Emmetropization in CNGB3 Achromatopsia’. Investigative Opthalmology & Visual Science, vol. 62, no. 2, Feb. 2021, p. 10. DOI.org (Crossref), https://doi.org/10.1167/iovs.62.2.10.
• Kohl S, Jägle H, Wissinger B, et al. Achromatopsia. 2004 Jun 24 [Updated 2018 Sep 20]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1418/
• Perez G, Barber GP, Benet-Pages A, Casper J, Clawson H, Diekhans M, Fischer C, Gonzalez JN, Hinrichs AS, Lee CM, Nassar LR, Raney BJ, Speir ML, van Baren MJ, Vaske CJ, Haussler D, Kent WJ, Haeussler M. The UCSC Genome Browser database: 2025 update. Nucleic Acids Res. 2025 Jan 6;53(D1):D1243-D1249. doi: 10.1093/nar/gkae974. PMID: 39460617; PMCID: PMC11701590.

キーワード｜Keywords

^{Achromatopsia, CNGB3, アクロマトプシア, Rod Monochromacy, 全色盲, 色覚異常, 錐体細胞, 眼振, 羞明, 視力低下, c.1148delC, 遺伝子治療, ERG, OCT, 網膜ジストロフィー, 遺伝性網膜疾患, 常染色体劣性遺伝, 網膜構造異常, 屈折異常, 幹細胞治療}