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Achromatopsia 4(ACHM4)

MedGen UID:
330669
Concept ID:
C1841721
Disease or Syndrome
Synonym: ACHM4
 
Gene (location): GNAT2 (1p13.3)
 
Monarch Initiative: MONDO:0013465
OMIM®: 613856

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 descriptions

From OMIM
Achromatopsia, also referred to as rod monochromacy, is an autosomal recessive ocular disorder characterized by total colorblindness, low visual acuity, photophobia, and nystagmus (Kohl et al., 2002). For a general description and a discussion of genetic heterogeneity of achromatopsia, see 216900.  http://www.omim.org/entry/613856
From MedlinePlus Genetics
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.

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 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.  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.
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.
Visual impairment
MedGen UID:
777085
Concept ID:
C3665347
Finding
Visual impairment (or vision impairment) is vision loss (of a person) to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive correction, medication, or surgery.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Professional guidelines

PubMed

Singh SR, Vaidya H, Borrelli E, Chhablani J
Surv Ophthalmol 2023 Jul-Aug;68(4):655-668. Epub 2023 Mar 18 doi: 10.1016/j.survophthal.2023.03.003. PMID: 36934831
Poonam NS, Alam MS, Oberoi P, Mukherjee B
Indian J Ophthalmol 2022 Dec;70(12):4419-4426. doi: 10.4103/ijo.IJO_719_22. PMID: 36453357Free PMC Article
Sheck LHN, Esposti SD, Mahroo OA, Arno G, Pontikos N, Wright G, Webster AR, Khan KN, Michaelides M
Mol Genet Genomic Med 2021 Dec;9(12):e1663. Epub 2021 Mar 22 doi: 10.1002/mgg3.1663. PMID: 33749171Free PMC Article

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

Singh SR, Vaidya H, Borrelli E, Chhablani J
Surv Ophthalmol 2023 Jul-Aug;68(4):655-668. Epub 2023 Mar 18 doi: 10.1016/j.survophthal.2023.03.003. PMID: 36934831
Sheck LHN, Esposti SD, Mahroo OA, Arno G, Pontikos N, Wright G, Webster AR, Khan KN, Michaelides M
Mol Genet Genomic Med 2021 Dec;9(12):e1663. Epub 2021 Mar 22 doi: 10.1002/mgg3.1663. PMID: 33749171Free PMC Article
Eghrari AO, Bishop RJ, Ross RD, Davis B, Larbelee J, Amegashie F, Dolo RF, Prakalapakorn SG, Gaisie C, Gargu C, Sosu Y, Sackor J, Cooper PZ, Wallace A, Nyain R, Gray M, Kamara F, Burkholder B, Brady CJ, Ray V, Tawse KL, Yeung I, Neaton JD, Higgs ES, Lane HC, Reilly C, Sneller MC, Fallah MP
JAMA Netw Open 2021 Jan 4;4(1):e2032216. doi: 10.1001/jamanetworkopen.2020.32216. PMID: 33399856Free 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
Yam JC, Kwok AK
Hong Kong Med J 2006 Aug;12(4):294-304. PMID: 16912357

Diagnosis

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
Sheck LHN, Esposti SD, Mahroo OA, Arno G, Pontikos N, Wright G, Webster AR, Khan KN, Michaelides M
Mol Genet Genomic Med 2021 Dec;9(12):e1663. Epub 2021 Mar 22 doi: 10.1002/mgg3.1663. PMID: 33749171Free PMC Article
Barboni MTS, Hauzman E, Nagy BV, Martins CMG, Aher AJ, Tsai TI, Bonci DMO, Ventura DF, Kremers J
Vision Res 2019 May;158:135-145. Epub 2019 Mar 7 doi: 10.1016/j.visres.2019.02.011. PMID: 30844384
Pedersen HR, Hagen LA, Landsend ECS, Gilson SJ, Utheim ØA, Utheim TP, Neitz M, Baraas RC
Invest Ophthalmol Vis Sci 2018 Apr 1;59(5):2142-2152. doi: 10.1167/iovs.17-23047. PMID: 29801149Free PMC Article
Regan D
J Opt Soc Am 1977 Nov;67(11):1475-89. doi: 10.1364/josa.67.001475. PMID: 411904

Therapy

Tirpack AR, Vanner EA, Sheheitli H, Mendoza CE, Grajewski A, Chang TC
J Glaucoma 2020 Feb;29(2):117-123. doi: 10.1097/IJG.0000000000001416. PMID: 31821182
Hassall MM, Barnard AR, MacLaren RE
Yale J Biol Med 2017 Dec;90(4):543-551. Epub 2017 Dec 19 PMID: 29259520Free PMC Article
Sengillo JD, Justus S, Tsai YT, Cabral T, Tsang SH
Am J Med Genet C Semin Med Genet 2016 Dec;172(4):349-366. Epub 2016 Nov 8 doi: 10.1002/ajmg.c.31534. PMID: 27862925Free PMC Article
Yam JC, Kwok AK
Hong Kong Med J 2006 Aug;12(4):294-304. PMID: 16912357
Jones WT, Kipling MD
Br J Ind Med 1972 Oct;29(4):460-1. doi: 10.1136/oem.29.4.460. PMID: 4539087Free PMC Article

Prognosis

Singh SR, Vaidya H, Borrelli E, Chhablani J
Surv Ophthalmol 2023 Jul-Aug;68(4):655-668. Epub 2023 Mar 18 doi: 10.1016/j.survophthal.2023.03.003. PMID: 36934831
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
Sheck LHN, Esposti SD, Mahroo OA, Arno G, Pontikos N, Wright G, Webster AR, Khan KN, Michaelides M
Mol Genet Genomic Med 2021 Dec;9(12):e1663. Epub 2021 Mar 22 doi: 10.1002/mgg3.1663. PMID: 33749171Free PMC Article
Bayer L, Funk J, Töteberg-Harms M
Int Ophthalmol 2020 Mar;40(3):597-605. Epub 2019 Nov 8 doi: 10.1007/s10792-019-01218-1. PMID: 31705359
Yam JC, Kwok AK
Hong Kong Med J 2006 Aug;12(4):294-304. PMID: 16912357

Clinical prediction guides

Lankford HV, Hovis JK
Wilderness Environ Med 2023 Dec;34(4):610-617. Epub 2023 Sep 27 doi: 10.1016/j.wem.2023.08.003. PMID: 37775373
Singh SR, Vaidya H, Borrelli E, Chhablani J
Surv Ophthalmol 2023 Jul-Aug;68(4):655-668. Epub 2023 Mar 18 doi: 10.1016/j.survophthal.2023.03.003. PMID: 36934831
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
Sheck LHN, Esposti SD, Mahroo OA, Arno G, Pontikos N, Wright G, Webster AR, Khan KN, Michaelides M
Mol Genet Genomic Med 2021 Dec;9(12):e1663. Epub 2021 Mar 22 doi: 10.1002/mgg3.1663. PMID: 33749171Free 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

Recent systematic reviews

Bailey KGH, Carter T
Occup Med (Lond) 2016 Jun;66(4):268-275. doi: 10.1093/occmed/kqw012. PMID: 27162253

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