Summary of the clinical, genetic and electrophysiological characteristics of the cone dysfunction syndromes
| Syndrome | Prevalence | Mode of inheritance | Typical BCVA (logMAR) | Typical refractive error | Nystagmus | Fundus findings | Colour vision | Typical ERG findings | Functional photoreceptors | Associated gene(s) (cytogenetic location) | Successful rescue of animal model/s |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Complete achromatopsia syn. typical achromatopsia; rod monochromatism | 1 in 30 000 | Autosomal recessive | 1.0 | Often hypermetropic | Present | Usually normal | Absent | Absent cone responses; often normal rod responses | LW-cones: no MW-cones: no SW-cones: no Rods: yes | CNGA3 (2q11.2) CNGB3 (8q21-q22) GNAT2 (1p13) PDE6C (10q24) PDE6H (12p13) | Yes |
| Incomplete achromatopsia syn. atypical achromatopsia | Uncertain | Autosomal recessive | 0.6–1.0 | Often hypermetropic | Present | Usually normal | Residual | Reduced or absent cone responses; often normal rod responses | LW-cones: possible MW-cones: possible SW-cones: possible Rods: yes | CNGA3 (2q11.2) CNGB3 (8q21-q22) GNAT2 (1p13) | Yes |
| Blue-cone monochromatism syn. S-cone monochromatism; X-linked incomplete achromatopsia; X-linked atypical achromatopsia | 1 in 100 000 | X-linked recessive | 0.6–1.0 | Often myopic | Present | Usually myopic | Residual tritan discrimination | Reduced cone responses but with preserved S-cone responses; normal rod responses | LW-cones: no MW-cones: no SW-cones: yes Rods: yes | Principal opsin array mutational mechanisms on Xq28: (i) LCR deletion (approx. 40% cases) (ii) Non-homologous recombination between OPN1LW/OPN1MW resulting in a single gene in the array with a subsequent inactivating point mutation (approximately 60% of cases) | Yes |
| Oligocone trichromacy | Uncertain | Autosomal recessive | 0.2–0.6 | Equal prevalence of myopia and hypermetropia | Often absent | Normal | Normal | Reduced or absent cone responses; normal rod responses | LW-cones: yes MW-cones: yes SW-cones: yes Rods: yes | Possibly hypomorphic variants in the genes associated with achromatopsia | No |
| Bradyopsia syn. RGS9/R9AP-retinopathy | Rare | Autosomal recessive | 0.2–0.6 | Equal prevalence of myopia and hypermetropia | Often absent | Normal | Normal | Reduced/absent cone responses; the rod-specific ERG and the SBWF with ISI of 2 min are normal—however, the SBWF ERG with an ISCEV standard ISI of 20 s shows amplitude reduction, which is progressively less severe with increasing ISI, consistent with delayed recovery following the flash—thereby demonstrating the need for more extended testing than that mandated by ISCEV in the ERG Standard protocol | LW-cones: yes MW-cones: yes SW-cones: yes Rods: yes | RGS9 (17q23-q24) R9AP (19q13.11) | No |
| Bornholm eye disease syn. X-linked cone dysfunction syndrome with dichromacy and myopia | Uncertain | X-linked recessive | 0–0.8 | Moderate to high myopia with astigmatism | Absent | Usually myopic | Deuteranopia or protanopia | Reduced cone responses; normal rod responses | LW-cones: yes, when observed with deuteranopia; no, when observed with protanopia MW-cones: yes, when observed with protanopia; no, when observed with deuteranopia SW-cones: yes Rods: yes | L/M interchange haplotypes (opsin array on Xq28) | No |
BCVA, best-corrected visual acuity; ERG, electroretinography; ISCEV, International Society for Clinical Electrophysiology of Vision; ISI, inter-stimulus interval; LCR, locus control region; logMAR, logarithm of the minimum angle of resolution; LW, long wavelength; MW, middle wavelength; SBWF, single bright white flash; SW, short wavelength; syn., synonym(s).