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Achromatopsia 3(ACHM3)

MedGen UID:
340413
Concept ID:
C1849792
Disease or Syndrome
Synonyms: ACHM1 (formerly); ACHM3; Achromatopsia with myopia; Pingelapese blindness; RMCH1 (formerly); ROD MONOCHROMACY 1; Rod monochromacy 1 (formerly); ROD MONOCHROMATISM 1; Rod monochromatism 1 (formerly); Total colorblindness with myopia
 
Gene (location): CNGB3 (8q21.3)
 
Monarch Initiative: MONDO:0009875
OMIM®: 262300

Disease characteristics

Excerpted from the GeneReview: Achromatopsia
Achromatopsia is characterized by reduced visual acuity, pendular nystagmus, increased sensitivity to light (photophobia), a small central scotoma, eccentric fixation, and reduced or complete loss of color discrimination. All individuals with achromatopsia (achromats) have impaired color discrimination along all three axes of color vision corresponding to the three cone classes: the protan or long-wavelength-sensitive cone axis (red), the deutan or middle-wavelength-sensitive cone axis (green), and the tritan or short-wavelength-sensitive cone axis (blue). Most individuals have complete achromatopsia, with total lack of function of all three types of cones. Rarely, individuals have incomplete achromatopsia, in which one or more cone types may be partially functioning. The manifestations are similar to those of individuals with complete achromatopsia, but generally less severe. Hyperopia is common in achromatopsia. Nystagmus develops during the first few weeks after birth followed by increased sensitivity to bright light. Best visual acuity varies with severity of the disease; it is 20/200 or less in complete achromatopsia and may be as high as 20/80 in incomplete achromatopsia. Visual acuity is usually stable over time; both nystagmus and sensitivity to bright light may improve slightly. Although the fundus is usually normal, macular changes (which may show early signs of progression) and vessel narrowing may be present in some affected individuals. Defects in the macula are visible on optical coherence tomography. [from GeneReviews]
Authors:
Susanne Kohl  |  Herbert Jägle  |  Bernd Wissinger, et. al.   view full author information

Additional description

From MedlinePlus Genetics
Achromatopsia is a condition characterized by a partial or total absence of color vision. People with complete achromatopsia cannot perceive any colors; they see only black, white, and shades of gray. Incomplete achromatopsia is a milder form of the condition that allows some color discrimination.

Achromatopsia also involves other problems with vision, including an increased sensitivity to light and glare (photophobia), involuntary back-and-forth eye movements (nystagmus), and significantly reduced sharpness of vision (low visual acuity). Affected individuals can also have farsightedness (hyperopia) or, less commonly, nearsightedness (myopia). These vision problems develop in the first few months of life.

Achromatopsia is different from the more common forms of color vision deficiency (also called color blindness), in which people can perceive color but have difficulty distinguishing between certain colors, such as red and green.  https://medlineplus.gov/genetics/condition/achromatopsia

Clinical features

From HPO
Photophobia
MedGen UID:
43220
Concept ID:
C0085636
Sign or Symptom
Excessive sensitivity to light with the sensation of discomfort or pain in the eyes due to exposure to bright light.
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.
Cataract
MedGen UID:
39462
Concept ID:
C0086543
Disease or Syndrome
A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule.
Achromatopsia
MedGen UID:
57751
Concept ID:
C0152200
Disease or Syndrome
Achromatopsia is characterized by reduced visual acuity, pendular nystagmus, increased sensitivity to light (photophobia), a small central scotoma, eccentric fixation, and reduced or complete loss of color discrimination. All individuals with achromatopsia (achromats) have impaired color discrimination along all three axes of color vision corresponding to the three cone classes: the protan or long-wavelength-sensitive cone axis (red), the deutan or middle-wavelength-sensitive cone axis (green), and the tritan or short-wavelength-sensitive cone axis (blue). Most individuals have complete achromatopsia, with total lack of function of all three types of cones. Rarely, individuals have incomplete achromatopsia, in which one or more cone types may be partially functioning. The manifestations are similar to those of individuals with complete achromatopsia, but generally less severe. Hyperopia is common in achromatopsia. Nystagmus develops during the first few weeks after birth followed by increased sensitivity to bright light. Best visual acuity varies with severity of the disease; it is 20/200 or less in complete achromatopsia and may be as high as 20/80 in incomplete achromatopsia. Visual acuity is usually stable over time; both nystagmus and sensitivity to bright light may improve slightly. Although the fundus is usually normal, macular changes (which may show early signs of progression) and vessel narrowing may be present in some affected individuals. Defects in the macula are visible on optical coherence tomography.
High myopia
MedGen UID:
78759
Concept ID:
C0271183
Disease or Syndrome
A severe form of myopia with greater than -6.00 diopters.
Dyschromatopsia
MedGen UID:
163559
Concept ID:
C0858618
Disease or Syndrome
A form of colorblindness in which only two of the three fundamental colors can be distinguished due to a lack of one of the retinal cone pigments.
Severely reduced visual acuity
MedGen UID:
226987
Concept ID:
C1301509
Disease or Syndrome
Severe reduction of the ability to see. On the 6m visual acuity scale, severe reduction is defined as less than 6/60 but at least 3/60. On the 20ft visual acuity scale, severe reduction is defined as less than 20/200 but at least 20/400. On the decimal visual acuity scale, severe reduction is defined as less than 0.1 but at least 0.05.
Moderately reduced visual acuity
MedGen UID:
723196
Concept ID:
C1301510
Finding
Moderate reduction of the ability to see. On the 6m visual acuity scale, moderate reduction is defined as less than 6/18 but at least 6/60. On the 20ft visual acuity scale, moderate reduction is defined as less than 20/70 but at least 20/200. On the decimal visual acuity scale, moderate reduction is defined as less than 0.3 but at least 0.1.
Horizontal pendular nystagmus
MedGen UID:
356175
Concept ID:
C1866180
Congenital Abnormality
Nystagmus consisting of horizontal to-and-fro eye movements of equal velocity.
Monochromacy
MedGen UID:
1684677
Concept ID:
C5201048
Disease or Syndrome
Complete color blindness, a complete inability to distinguish colors. Affected persons cannot perceive colors, but only shades of gray.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Professional guidelines

PubMed

Pascual-Camps I, Barranco-Gonzalez H, Aviñó-Martínez J, Silva E, Harto-Castaño M
J Pediatr Ophthalmol Strabismus 2018 Mar 1;55(2):85-92. Epub 2017 Dec 19 doi: 10.3928/01913913-20171117-01. PMID: 29257187

Curated

Kohl S, Hamel CP
Eur J Hum Genet 2011 Jun;19(6) Epub 2011 Jan 26 doi: 10.1038/ejhg.2010.231. PMID: 21267001Free PMC Article

Recent clinical studies

Etiology

Molz B, Herbik A, Baseler HA, de Best P, Raz N, Gouws A, Ahmadi K, Lowndes R, McLean RJ, Gottlob I, Kohl S, Choritz L, Maguire J, Kanowski M, Käsmann-Kellner B, Wieland I, Banin E, Levin N, Morland AB, Hoffmann MB
Invest Ophthalmol Vis Sci 2023 Oct 3;64(13):23. doi: 10.1167/iovs.64.13.23. PMID: 37847226Free PMC Article
Michaelides M, Hirji N, Wong SC, Besirli CG, Zaman S, Kumaran N, Georgiadis A, Smith AJ, Ripamonti C, Gottlob I, Robson AG, Thiadens A, Henderson RH, Fleck P, Anglade E, Dong X, Capuano G, Lu W, Berry P, Kane T, Naylor S, Georgiou M, Kalitzeos A, Ali RR, Forbes A, Bainbridge J
Am J Ophthalmol 2023 Sep;253:243-251. Epub 2023 May 11 doi: 10.1016/j.ajo.2023.05.009. PMID: 37172884
Andersen MKG, Kessel L
Invest Ophthalmol Vis Sci 2021 Feb 1;62(2):10. doi: 10.1167/iovs.62.2.10. PMID: 33560291Free PMC Article
Georgiou M, Robson AG, Singh N, Pontikos N, Kane T, Hirji N, Ripamonti C, Rotsos T, Dubra A, Kalitzeos A, Webster AR, Carroll J, Michaelides M
Invest Ophthalmol Vis Sci 2019 Dec 2;60(15):5112-5123. doi: 10.1167/iovs.19-27761. PMID: 31826238Free PMC Article
Tsang SH, Sharma T
Adv Exp Med Biol 2018;1085:119-123. doi: 10.1007/978-3-319-95046-4_24. PMID: 30578497

Diagnosis

Michaelides M, Hirji N, Wong SC, Besirli CG, Zaman S, Kumaran N, Georgiadis A, Smith AJ, Ripamonti C, Gottlob I, Robson AG, Thiadens A, Henderson RH, Fleck P, Anglade E, Dong X, Capuano G, Lu W, Berry P, Kane T, Naylor S, Georgiou M, Kalitzeos A, Ali RR, Forbes A, Bainbridge J
Am J Ophthalmol 2023 Sep;253:243-251. Epub 2023 May 11 doi: 10.1016/j.ajo.2023.05.009. PMID: 37172884
Kuht HJ, Maconachie GDE, Han J, Kessel L, van Genderen MM, McLean RJ, Hisaund M, Tu Z, Hertle RW, Gronskov K, Bai D, Wei A, Li W, Jiao Y, Smirnov V, Choi JH, Tobin MD, Sheth V, Purohit R, Dawar B, Girach A, Strul S, May L, Chen FK, Heath Jeffery RC, Aamir A, Sano R, Jin J, Brooks BP, Kohl S, Arveiler B, Montoliu L, Engle EC, Proudlock FA, Nishad G, Pani P, Varma G, Gottlob I, Thomas MG
Ophthalmology 2022 Jun;129(6):708-718. Epub 2022 Feb 11 doi: 10.1016/j.ophtha.2022.02.010. PMID: 35157951Free PMC Article
Georgiou M, Robson AG, Singh N, Pontikos N, Kane T, Hirji N, Ripamonti C, Rotsos T, Dubra A, Kalitzeos A, Webster AR, Carroll J, Michaelides M
Invest Ophthalmol Vis Sci 2019 Dec 2;60(15):5112-5123. doi: 10.1167/iovs.19-27761. PMID: 31826238Free PMC Article
Pascual-Camps I, Barranco-Gonzalez H, Aviñó-Martínez J, Silva E, Harto-Castaño M
J Pediatr Ophthalmol Strabismus 2018 Mar 1;55(2):85-92. Epub 2017 Dec 19 doi: 10.3928/01913913-20171117-01. PMID: 29257187
Schallhorn CS, Granet DB, Ferreyra HA
Retin Cases Brief Rep 2018 Spring;12(2):143-148. doi: 10.1097/ICB.0000000000000451. PMID: 27820752

Therapy

Michaelides M, Hirji N, Wong SC, Besirli CG, Zaman S, Kumaran N, Georgiadis A, Smith AJ, Ripamonti C, Gottlob I, Robson AG, Thiadens A, Henderson RH, Fleck P, Anglade E, Dong X, Capuano G, Lu W, Berry P, Kane T, Naylor S, Georgiou M, Kalitzeos A, Ali RR, Forbes A, Bainbridge J
Am J Ophthalmol 2023 Sep;253:243-251. Epub 2023 May 11 doi: 10.1016/j.ajo.2023.05.009. PMID: 37172884
Reichel FF, Michalakis S, Wilhelm B, Zobor D, Muehlfriedel R, Kohl S, Weisschuh N, Sothilingam V, Kuehlewein L, Kahle N, Seitz I, Paquet-Durand F, Tsang SH, Martus P, Peters T, Seeliger M, Bartz-Schmidt KU, Ueffing M, Zrenner E, Biel M, Wissinger B, Fischer D
Br J Ophthalmol 2022 Nov;106(11):1567-1572. Epub 2021 May 18 doi: 10.1136/bjophthalmol-2021-319067. PMID: 34006508
Lee EJ, Chiang WJ, Kroeger H, Bi CX, Chao DL, Skowronska-Krawczyk D, Mastey RR, Tsang SH, Chea L, Kim K, Lambert SR, Grandjean JM, Baumann B, Audo I, Kohl S, Moore AT, Wiseman RL, Carroll J, Lin JH
JCI Insight 2020 Apr 9;5(7) doi: 10.1172/jci.insight.136041. PMID: 32271167Free PMC Article
Zobor D, Werner A, Stanzial F, Benedicenti F, Rudolph G, Kellner U, Hamel C, Andréasson S, Zobor G, Strasser T, Wissinger B, Kohl S, Zrenner E; RD-CURE Consortium
Invest Ophthalmol Vis Sci 2017 Feb 1;58(2):821-832. doi: 10.1167/iovs.16-20427. PMID: 28159970
Langlo CS, Erker LR, Parker M, Patterson EJ, Higgins BP, Summerfelt P, Razeen MM, Collison FT, Fishman GA, Kay CN, Zhang J, Weleber RG, Yang P, Pennesi ME, Lam BL, Chulay JD, Dubra A, Hauswirth WW, Wilson DJ, Carroll J; ACHM-001 study group
Retina 2017 Oct;37(10):1956-1966. doi: 10.1097/IAE.0000000000001434. PMID: 28145975Free PMC Article

Prognosis

Andersen MKG, Bertelsen M, Grønskov K, Kohl S, Kessel L
Genes (Basel) 2023 Mar 10;14(3) doi: 10.3390/genes14030690. PMID: 36980963Free PMC Article
Reuter P, Walter M, Kohl S, Weisschuh N
Sci Rep 2023 Feb 18;13(1):2896. doi: 10.1038/s41598-023-29452-9. PMID: 36801918Free PMC Article
Kuht HJ, Maconachie GDE, Han J, Kessel L, van Genderen MM, McLean RJ, Hisaund M, Tu Z, Hertle RW, Gronskov K, Bai D, Wei A, Li W, Jiao Y, Smirnov V, Choi JH, Tobin MD, Sheth V, Purohit R, Dawar B, Girach A, Strul S, May L, Chen FK, Heath Jeffery RC, Aamir A, Sano R, Jin J, Brooks BP, Kohl S, Arveiler B, Montoliu L, Engle EC, Proudlock FA, Nishad G, Pani P, Varma G, Gottlob I, Thomas MG
Ophthalmology 2022 Jun;129(6):708-718. Epub 2022 Feb 11 doi: 10.1016/j.ophtha.2022.02.010. PMID: 35157951Free PMC Article
Andersen MKG, Kessel L
Invest Ophthalmol Vis Sci 2021 Feb 1;62(2):10. doi: 10.1167/iovs.62.2.10. PMID: 33560291Free PMC Article
Georgiou M, Robson AG, Singh N, Pontikos N, Kane T, Hirji N, Ripamonti C, Rotsos T, Dubra A, Kalitzeos A, Webster AR, Carroll J, Michaelides M
Invest Ophthalmol Vis Sci 2019 Dec 2;60(15):5112-5123. doi: 10.1167/iovs.19-27761. PMID: 31826238Free PMC Article

Clinical prediction guides

Amaral RAS, Motta FL, Zin OA, da Palma MM, Rodrigues GD, Sallum JMF
Genes (Basel) 2023 Jun 20;14(6) doi: 10.3390/genes14061296. PMID: 37372476Free PMC Article
Kuht HJ, Maconachie GDE, Han J, Kessel L, van Genderen MM, McLean RJ, Hisaund M, Tu Z, Hertle RW, Gronskov K, Bai D, Wei A, Li W, Jiao Y, Smirnov V, Choi JH, Tobin MD, Sheth V, Purohit R, Dawar B, Girach A, Strul S, May L, Chen FK, Heath Jeffery RC, Aamir A, Sano R, Jin J, Brooks BP, Kohl S, Arveiler B, Montoliu L, Engle EC, Proudlock FA, Nishad G, Pani P, Varma G, Gottlob I, Thomas MG
Ophthalmology 2022 Jun;129(6):708-718. Epub 2022 Feb 11 doi: 10.1016/j.ophtha.2022.02.010. PMID: 35157951Free PMC Article
Brunetti-Pierri R, Karali M, Melillo P, Di Iorio V, De Benedictis A, Iaccarino G, Testa F, Banfi S, Simonelli F
Int J Mol Sci 2021 Feb 7;22(4) doi: 10.3390/ijms22041681. PMID: 33562422Free PMC Article
Oh JK, Ryu J, Lima de Carvalho JR Jr, Levi SR, Lee W, Tsamis E, Greenstein VC, Mahajan VB, Allikmets R, Tsang SH
Am J Ophthalmol 2020 Oct;218:40-53. Epub 2020 May 21 doi: 10.1016/j.ajo.2020.05.016. PMID: 32445700Free PMC Article
Tsang SH, Sharma T
Adv Exp Med Biol 2018;1085:119-123. doi: 10.1007/978-3-319-95046-4_24. PMID: 30578497

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