Table 3.

Inherited Retinal Dystrophies to Consider in the Differential Diagnosis of Achromatopsia

DisorderGene(s)MOIOverlapping Clinical FeaturesDistinguishing Clinical FeaturesComments
Blue-cone monochromatism 1 (OMIM 303700)OPN1LW; OPN1MW 2XL 3
  • Severely ↓ visual acuity
  • Eccentric fixation
  • ± Infantile nystagmus
  • No obvious fundus abnormalities
  • Poor or no color discrimination 4
In blue-cone monochromatism:
  • Peak of photopic luminosity function is near 440 nm (the peak sensitivity of the S cones), not 507 nm (the peak sensitivity of the rods).
  • Mostly males are affected.
  • A special 4-color plate test or a 2-color filter test can clinically distinguish blue-cone monochromats from achromats (rod monochromats).
  • Cone ERG responses can be elicited by presenting blue flashes on a yellow background (because the S cones are functioning in addition to the rods).
Hereditary red-green color vision defects (OMIM 303800, 303900)OPN1LW, OPN1MWXLColor vision defects 5In hereditary red-green color vision defects:
  • Absence of ophthalmologic or other associated clinical abnormalities
  • Most individuals w/protanomalous & deuteranomalous color vision defects (i.e., anomalous trichromats) have no major problems in naming colors.
  • Mostly males are affected.
  • Clinical chart tests widely used to detect red-green color vision defects include Ishihara plates & the American Optical HRR pseudoisochromatic plates.
  • Definitive classification of color vision defects known as protanopia, deuteranopia, protanomaly, & deuteranomaly requires use of anomaloscope, which involves color matching.
Tritan and yellow-blue defects
(OMIM 190900)		 OPN1SW ADColor confusion

In tritan & yellow-blue defects: color confusion is limited to blues & greens. 6

Other non-congenital yellow-blue deficits (similar in some ways to tritan defects) may result from aging or disorders of choroid, pigment epithelium, retina, or optic nerve (e.g., optic atrophy type 1; OMIM 165500); they are usually progressive & have other related signs; e.g. associated visual acuity defects. 7
Cone / cone-rod dystrophies 8ABCA4, AIPL1, CABP4, CNNM4, CDHR1, GUCY2D, KCNV2, RAB28, RPGRIP1AD, AR
  • Cone function may be normal at birth.
  • Typical symptoms (↓ visual acuity, photophobia, ↑ sensitivity to glare, abnormal color vision) appear later. 9
  • Age of onset of vision loss may be as early as childhood or as late as 7th decade.
  • Dark-adapted rod thresholds may be elevated. 10
Disease progression occurs in cone dystrophy & typically not in achromatopsia.
  • Differentiating between achromatopsia & cone dystrophy can be difficult, particularly in individuals w/early-childhood onset.
  • Best clinical discriminator is disease progression.
Leber congenital amaurosis (LCA) AIPL1
CABP4
CEP290
GUCY2D
RPGRIP1 		AR
  • Infantile nystagmus
  • Photophobia
  • Severely reduced visual acuity
  • No obvious fundus abnormalities
  • Poor or no color discrimination
Night blindness & progression occur in LCA.In very young individuals
Bradyopsia; delayed cone adaptation RGS9
  • Prolonged electroretinal response suppression leading to difficulties adjusting to changes in luminance
  • Normal to subnormal visual acuity
  • Photophobia
Alström syndrome 11 ALMS1 AR
  • Infantile nystagmus
  • Photophobia
  • Severely reduced visual acuity
  • Poor or no color discrimination
Possible additional findings in Alström syndrome: cardiomyopathy, kidney failure, obesity, sensorineural hearing loss, diabetesIn young individuals

AD = autosomal dominant; AR = autosomal recessive; ERG = electroretinogram; MOI = mode of inheritance; XL = X-linked

1.

Blue-cone monochromacy may also be referred to as S-cone monochromacy or X-chromosome-linked achromatopsia.

2.

The dysfunction of the L (red) and M (green) cones is caused by pathogenic variants leading to the loss of the X-linked red (OPN1LW) and green (OPN1MW) opsin gene array, hybrid gene formation and/or inactivating variants, or by deletions affecting the locus control region, a critical region that regulates the expression of the red/green (OPN1LW/OPN1MW) gene array.

3.

Blue-cone monochromacy affects mostly males.

4.
5.

Some males with mildly defective red-green color vision may not be aware of it until they are tested. Among individuals of northern European origin, about 8% of males and 0.5% of females have red-green color vision defects; these defects are less frequent among males of African (3%-4%) or Asian (3%) origin.

6.

Often referred to as yellow-blue disorders, although the color confusion is typically between blues & greens, tritan defects affect the S (blue) cones.

7.
8.

See Glöckle et al [2014], Weisschuh et al [2016], Carss et al [2017] for genes identified in patients misdiagnosed as having achromatopsia.

9.
10.
11.

From: Achromatopsia

Cover of GeneReviews®
GeneReviews® [Internet].
Adam MP, Feldman J, Mirzaa GM, et al., editors.
Seattle (WA): University of Washington, Seattle; 1993-2024.
Copyright © 1993-2024, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

GeneReviews® chapters are owned by the University of Washington. Permission is hereby granted to reproduce, distribute, and translate copies of content materials for noncommercial research purposes only, provided that (i) credit for source (http://www.genereviews.org/) and copyright (© 1993-2024 University of Washington) are included with each copy; (ii) a link to the original material is provided whenever the material is published elsewhere on the Web; and (iii) reproducers, distributors, and/or translators comply with the GeneReviews® Copyright Notice and Usage Disclaimer. No further modifications are allowed. For clarity, excerpts of GeneReviews chapters for use in lab reports and clinic notes are a permitted use.

For more information, see the GeneReviews® Copyright Notice and Usage Disclaimer.

For questions regarding permissions or whether a specified use is allowed, contact: ude.wu@tssamda.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.