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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

Authors:

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
There 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\nThe 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\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

Bianco L, Arrigo A, Antropoli A, Manitto MP, Martina E, Aragona E, Bandello F, Battaglia Parodi M
JAMA Ophthalmol 2023 Sep 1;141(9):826-833. doi: 10.1001/jamaophthalmol.2023.3188. PMID: 37498587Free PMC Article
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
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

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

Tsang SH, Aycinena ARP, Sharma T
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Tsang SH, Sharma T
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Jiang F, Pan Z, Xu K, Tian L, Xie Y, Zhang X, Chen J, Dong B, Li Y
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Benjamin J, Ebstein RP, Belmaker RH
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Diagnosis

Sawa M
Jpn J Ophthalmol 2024 Jul;68(4):259-292. Epub 2024 Jul 16 doi: 10.1007/s10384-024-01075-1. PMID: 39012573
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
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Hamel C
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Therapy

Hassall MM, Barnard AR, MacLaren RE
Yale J Biol Med 2017 Dec;90(4):543-551. Epub 2017 Dec 19 PMID: 29259520Free PMC Article
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Prognosis

Fenner BJ, Whitmore SS, DeLuca AP, Andorf JL, Daggett HT, Luse MA, Haefeli LM, Riley JB, Critser DB, Wilkinson ME, Dumitrescu AV, Drack AV, Boyce TM, Russell JF, Binkley EM, Sohn EH, Russell SR, Boldt HC, Mullins RF, Tucker BA, Scheetz TE, Han IC, Stone EM
Ophthalmology 2024 Aug;131(8):985-997. Epub 2024 Feb 1 doi: 10.1016/j.ophtha.2024.01.035. PMID: 38309476Free PMC Article
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
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

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 K, Gotmare ND, Bhattacharyya M
Indian J Ophthalmol 2022 Jan;70(1):261-265. doi: 10.4103/ijo.IJO_1696_21. PMID: 34937251Free PMC Article
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
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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