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Cone dystrophy 4(COD4)

MedGen UID:
416518
Concept ID:
C2751308
Disease or Syndrome
Synonyms: COD4; Cone-Rod Dystrophy 4
 
Gene (location): PDE6C (10q23.33)
 
Monarch Initiative: MONDO:0013129
OMIM®: 613093

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 OMIM
Cone photoreceptor disorders form a clinical spectrum of diseases that include progressive cone dystrophy (COD) and complete and incomplete achromatopsia (ACHM). Impairment or death of cone photoreceptor cells is the clinical hallmark of these disorders. COD is a progressive cone disorder in which patients may initially have normal cone function but develop progressive visual acuity loss, increasing photophobia, color vision disturbances, and diminished cone responses on ERG, usually in the first or second decade of life. The visual acuity of these patients generally worsens to legal blindness before the fourth decade of life. ACHM is a stationary congenital autosomal recessive cone disorder characterized by low visual acuity, photophobia, nystagmus, and severe color vision defects. Patients with the complete ACHM subtype have no cone function on electroretinography, whereas those with incomplete ACHM show residual cone function (summary by Thiadens et al., 2009).  http://www.omim.org/entry/613093

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.
Reduced visual acuity
MedGen UID:
65889
Concept ID:
C0234632
Finding
Diminished clarity of vision.
Absent foveal reflex
MedGen UID:
602333
Concept ID:
C0423420
Finding
Lack of the foveal reflex, which normally occurs as a result of the reflection of light from the ophthalmoscope in the foveal pit upon examination. The foveal reflex is a bright pinpoint of light that is observed to move sideways or up and down in response to movement of the opthalmoscope.
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.
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.
Undetectable light-adapted electroretinogram
MedGen UID:
893040
Concept ID:
C4072955
Finding
No detectable response to the light-adapted 3.0 ERG (single-flash cone response). This type of ERG measures responses of the cone system; a-waves arise from cone photoreceptors and cone off-bipolar cells; the b-wave comes from On- and Off-cone bipolar cells.
Cone-rod dystrophy
MedGen UID:
896366
Concept ID:
C4085590
Disease or Syndrome
The first signs and symptoms of cone-rod dystrophy, which often occur in childhood, are usually decreased sharpness of vision (visual acuity) and increased sensitivity to light (photophobia). These features are typically followed by impaired color vision (dyschromatopsia), blind spots (scotomas) in the center of the visual field, and partial side (peripheral) vision loss. Over time, affected individuals develop night blindness and a worsening of their peripheral vision, which can limit independent mobility. Decreasing visual acuity makes reading increasingly difficult and most affected individuals are legally blind by mid-adulthood. As the condition progresses, individuals may develop involuntary eye movements (nystagmus).\n\nThere are more than 30 types of cone-rod dystrophy, which are distinguished by their genetic cause and their pattern of inheritance: autosomal recessive, autosomal dominant, and X-linked. Additionally, cone-rod dystrophy can occur alone without any other signs and symptoms or it can occur as part of a syndrome that affects multiple parts of the body.\n\nCone-rod dystrophy is a group of related eye disorders that causes vision loss, which becomes more severe over time. These disorders affect the retina, which is the layer of light-sensitive tissue at the back of the eye. In people with cone-rod dystrophy, vision loss occurs as the light-sensing cells of the retina gradually deteriorate.

Professional guidelines

PubMed

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Xiao X, Ye L, Chen C, Zheng H, Yuan J
Curr Gene Ther 2022;22(4):342-351. doi: 10.2174/1566523222666220216101539. PMID: 35170407Free PMC Article
Zhang F, Kurokawa K, Bernucci MT, Jung HW, Lassoued A, Crowell JA, Neitz J, Neitz M, Miller DT
Invest Ophthalmol Vis Sci 2021 Feb 1;62(2):8. doi: 10.1167/iovs.62.2.8. PMID: 33544131Free 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

Fardeau C, Alafaleq M, Dhaenens CM, Dollfus H, Koné-Paut I, Grunewald O, Morel JB, Titah C, Saadoun D, Lazeran PO, Meunier I
Clin Genet 2023 Apr;103(4):453-458. Epub 2022 Dec 30 doi: 10.1111/cge.14286. PMID: 36543582
Fischer MD, Michalakis S, Wilhelm B, Zobor D, Muehlfriedel R, Kohl S, Weisschuh N, Ochakovski GA, Klein R, Schoen C, Sothilingam V, Garcia-Garrido M, Kuehlewein L, Kahle N, Werner A, Dauletbekov D, Paquet-Durand F, Tsang S, Martus P, Peters T, Seeliger M, Bartz-Schmidt KU, Ueffing M, Zrenner E, Biel M, Wissinger B
JAMA Ophthalmol 2020 Jun 1;138(6):643-651. doi: 10.1001/jamaophthalmol.2020.1032. PMID: 32352493Free PMC Article
Tsang SH, Aycinena ARP, Sharma T
Adv Exp Med Biol 2018;1085:167-170. doi: 10.1007/978-3-319-95046-4_32. PMID: 30578505
Tsang SH, Sharma T
Adv Exp Med Biol 2018;1085:119-123. doi: 10.1007/978-3-319-95046-4_24. PMID: 30578497
Jiang F, Pan Z, Xu K, Tian L, Xie Y, Zhang X, Chen J, Dong B, Li Y
Invest Ophthalmol Vis Sci 2016 Jan 1;57(1):145-52. doi: 10.1167/iovs.15-18190. PMID: 26780318

Diagnosis

Fardeau C, Alafaleq M, Dhaenens CM, Dollfus H, Koné-Paut I, Grunewald O, Morel JB, Titah C, Saadoun D, Lazeran PO, Meunier I
Clin Genet 2023 Apr;103(4):453-458. Epub 2022 Dec 30 doi: 10.1111/cge.14286. PMID: 36543582
Fischer MD, Michalakis S, Wilhelm B, Zobor D, Muehlfriedel R, Kohl S, Weisschuh N, Ochakovski GA, Klein R, Schoen C, Sothilingam V, Garcia-Garrido M, Kuehlewein L, Kahle N, Werner A, Dauletbekov D, Paquet-Durand F, Tsang S, Martus P, Peters T, Seeliger M, Bartz-Schmidt KU, Ueffing M, Zrenner E, Biel M, Wissinger B
JAMA Ophthalmol 2020 Jun 1;138(6):643-651. doi: 10.1001/jamaophthalmol.2020.1032. PMID: 32352493Free PMC Article
Zampaglione E, Kinde B, Place EM, Navarro-Gomez D, Maher M, Jamshidi F, Nassiri S, Mazzone JA, Finn C, Schlegel D, Comander J, Pierce EA, Bujakowska KM
Genet Med 2020 Jun;22(6):1079-1087. Epub 2020 Feb 10 doi: 10.1038/s41436-020-0759-8. PMID: 32037395Free 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
Hamel C
Orphanet J Rare Dis 2006 Oct 11;1:40. doi: 10.1186/1750-1172-1-40. PMID: 17032466Free PMC Article

Therapy

Rigaudière F, Nasser H, Delouvrier E, Milani P, Schiff M
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Fischer MD, Michalakis S, Wilhelm B, Zobor D, Muehlfriedel R, Kohl S, Weisschuh N, Ochakovski GA, Klein R, Schoen C, Sothilingam V, Garcia-Garrido M, Kuehlewein L, Kahle N, Werner A, Dauletbekov D, Paquet-Durand F, Tsang S, Martus P, Peters T, Seeliger M, Bartz-Schmidt KU, Ueffing M, Zrenner E, Biel M, Wissinger B
JAMA Ophthalmol 2020 Jun 1;138(6):643-651. doi: 10.1001/jamaophthalmol.2020.1032. PMID: 32352493Free PMC Article
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
Jones WT, Kipling MD
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Prognosis

Ma DJ, Lee HS, Kim K, Choi S, Jang I, Cho SH, Yoon CK, Lee EK, Yu HG
BMC Med Genomics 2021 Mar 10;14(1):74. doi: 10.1186/s12920-021-00874-6. PMID: 33691693Free PMC Article
Fischer MD, Michalakis S, Wilhelm B, Zobor D, Muehlfriedel R, Kohl S, Weisschuh N, Ochakovski GA, Klein R, Schoen C, Sothilingam V, Garcia-Garrido M, Kuehlewein L, Kahle N, Werner A, Dauletbekov D, Paquet-Durand F, Tsang S, Martus P, Peters T, Seeliger M, Bartz-Schmidt KU, Ueffing M, Zrenner E, Biel M, Wissinger B
JAMA Ophthalmol 2020 Jun 1;138(6):643-651. doi: 10.1001/jamaophthalmol.2020.1032. PMID: 32352493Free PMC Article
Zampaglione E, Kinde B, Place EM, Navarro-Gomez D, Maher M, Jamshidi F, Nassiri S, Mazzone JA, Finn C, Schlegel D, Comander J, Pierce EA, Bujakowska KM
Genet Med 2020 Jun;22(6):1079-1087. Epub 2020 Feb 10 doi: 10.1038/s41436-020-0759-8. PMID: 32037395Free PMC Article
Jiang F, Pan Z, Xu K, Tian L, Xie Y, Zhang X, Chen J, Dong B, Li Y
Invest Ophthalmol Vis Sci 2016 Jan 1;57(1):145-52. doi: 10.1167/iovs.15-18190. PMID: 26780318
Hamel C
Orphanet J Rare Dis 2006 Oct 11;1:40. doi: 10.1186/1750-1172-1-40. PMID: 17032466Free PMC Article

Clinical prediction guides

Fardeau C, Alafaleq M, Dhaenens CM, Dollfus H, Koné-Paut I, Grunewald O, Morel JB, Titah C, Saadoun D, Lazeran PO, Meunier I
Clin Genet 2023 Apr;103(4):453-458. Epub 2022 Dec 30 doi: 10.1111/cge.14286. PMID: 36543582
Ma DJ, Lee HS, Kim K, Choi S, Jang I, Cho SH, Yoon CK, Lee EK, Yu HG
BMC Med Genomics 2021 Mar 10;14(1):74. doi: 10.1186/s12920-021-00874-6. PMID: 33691693Free PMC Article
Fischer MD, Michalakis S, Wilhelm B, Zobor D, Muehlfriedel R, Kohl S, Weisschuh N, Ochakovski GA, Klein R, Schoen C, Sothilingam V, Garcia-Garrido M, Kuehlewein L, Kahle N, Werner A, Dauletbekov D, Paquet-Durand F, Tsang S, Martus P, Peters T, Seeliger M, Bartz-Schmidt KU, Ueffing M, Zrenner E, Biel M, Wissinger B
JAMA Ophthalmol 2020 Jun 1;138(6):643-651. doi: 10.1001/jamaophthalmol.2020.1032. PMID: 32352493Free PMC Article
Zampaglione E, Kinde B, Place EM, Navarro-Gomez D, Maher M, Jamshidi F, Nassiri S, Mazzone JA, Finn C, Schlegel D, Comander J, Pierce EA, Bujakowska KM
Genet Med 2020 Jun;22(6):1079-1087. Epub 2020 Feb 10 doi: 10.1038/s41436-020-0759-8. PMID: 32037395Free 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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