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Corneal dystrophy, Fuchs endothelial, 1(FECD1)

MedGen UID:
338172
Concept ID:
C1850959
Disease or Syndrome
Synonyms: Corneal dystrophy Fuchs endothelial early-onset; Fuchs' endothelial dystrophy type 1
 
Gene (location): COL8A2 (1p34.3)
 
Monarch Initiative: MONDO:0007637
OMIM®: 136800

Definition

Fuchs endothelial corneal dystrophy (FECD) is a progressive, bilateral condition characterized by dysfunction of the corneal epithelium, leading to reduced vision. The prevalence of FECD has been estimated at about 5% among persons over the age of 40 years in the United States. The vision loss in patients with FECD results from a loss of corneal transparency associated with irregularity of inner corneal layers in early disease and edema of the cornea in advanced disease. Ultrastructural features of FECD include loss and attenuation of endothelial cells, with thickening and excrescences of the underlying basement membrane. These excrescences, called guttae, are the clinical hallmark of FECD and become more numerous with progression of the disease. As the endothelial layer develops confluent guttae in the central cornea, the cells are no longer able to keep the cornea dehydrated and clear (summary by Baratz et al., 2010). Genetic Heterogeneity of Fuchs Endothelial Corneal Dystrophy More common, late-onset forms of FECD have been shown to be caused by mutation in the SLC4A11 gene (610206) on chromosome 20p13 (FECD4; 613268), in the ZEB1 gene (189909) on chromosome 10p11.2 (FECD6; 613270), and in the AGBL1 gene (615496) on chromosome 15q25 (FECD8; 615523). Other loci for late-onset FECD have been identified on chromosomes 13pter-q12.13 (FECD2; 610158), 18q21.2-q21.32 (FECD3; 613267), 5q33.1-q35.2 (FECD5; 613269), and 9p (FECD7; 613271). [from OMIM]

Additional description

From MedlinePlus Genetics
Fuchs endothelial dystrophy is a condition that causes vision problems. The first symptom of this condition is typically blurred vision in the morning that usually clears during the day. Over time, affected individuals lose the ability to see details (visual acuity). People with Fuchs endothelial dystrophy also become sensitive to bright lights.

Fuchs endothelial dystrophy specifically affects the front surface of the eye called the cornea. Deposits called guttae, which are detectable during an eye exam, form in the middle of the cornea and eventually spread throughout the cornea. These guttae contribute to the ongoing cell death within the cornea, leading to worsening vision problems. Tiny blisters may develop on the cornea, which can burst and cause eye pain.

The signs and symptoms of Fuchs endothelial dystrophy usually begin in a person's forties or fifties. A very rare early-onset variant of this condition starts to affect vision in a person's twenties.  https://medlineplus.gov/genetics/condition/fuchs-endothelial-dystrophy

Clinical features

From HPO
Corneal dystrophy
MedGen UID:
3619
Concept ID:
C0010036
Disease or Syndrome
The term corneal dystrophy embraces a heterogenous group of bilateral genetically determined non-inflammatory corneal diseases that are restricted to the cornea.
Descemet Membrane Folds
MedGen UID:
509797
Concept ID:
C0155116
Anatomical Abnormality
Presence of folds in the Descemet membrane, which is the basement membrane of the endothelial (inner) cell layer of the cornea. Descemet membrane folds are generally a manifestation of inflammation or edema of the cornea.
Corneal degeneration
MedGen UID:
56352
Concept ID:
C0155118
Disease or Syndrome
Corneal guttata
MedGen UID:
488833
Concept ID:
C0271288
Finding
Corneal guttata are droplet-like accumulations of non-banded collagen on the posterior surface of Descemet's membrane. The presence of focal thickenings of Descemet's membrane histologically named guttae. Cornea guttata can be easily diagnosed in vivo and ex vivo by means of specular microscopy as it gives dark areas where no endothelial cells are visible.
Corneal stromal edema
MedGen UID:
96883
Concept ID:
C0474444
Finding
Abnormal accumulation of fluid and swelling of the stroma of cornea.

Recent clinical studies

Etiology

de Jong B, Brandi-Dohrn F, van der Meulen IJE, van den Berg TJTP, Wacker K
Cornea 2023 Feb 1;42(2):164-171. Epub 2022 Feb 4 doi: 10.1097/ICO.0000000000003002. PMID: 35120348
Kannabiran C, Chaurasia S, Ramappa M, Mootha VV
Indian J Ophthalmol 2022 Jul;70(7):2239-2248. doi: 10.4103/ijo.IJO_992_22. PMID: 35791103Free PMC Article
Maier PC, Reinhard T
Klin Monbl Augenheilkd 2022 Jun;239(6):767-774. Epub 2022 Apr 14 doi: 10.1055/a-1756-5199. PMID: 35426114
Afshari NA, Igo RP Jr, Morris NJ, Stambolian D, Sharma S, Pulagam VL, Dunn S, Stamler JF, Truitt BJ, Rimmler J, Kuot A, Croasdale CR, Qin X, Burdon KP, Riazuddin SA, Mills R, Klebe S, Minear MA, Zhao J, Balajonda E, Rosenwasser GO, Baratz KH, Mootha VV, Patel SV, Gregory SG, Bailey-Wilson JE, Price MO, Price FW Jr, Craig JE, Fingert JH, Gottsch JD, Aldave AJ, Klintworth GK, Lass JH, Li YJ, Iyengar SK
Nat Commun 2017 Mar 30;8:14898. doi: 10.1038/ncomms14898. PMID: 28358029Free PMC Article
Schmedt T, Silva MM, Ziaei A, Jurkunas U
Exp Eye Res 2012 Feb;95(1):24-34. Epub 2011 Aug 10 doi: 10.1016/j.exer.2011.08.002. PMID: 21855542Free PMC Article

Diagnosis

Kannabiran C, Chaurasia S, Ramappa M, Mootha VV
Indian J Ophthalmol 2022 Jul;70(7):2239-2248. doi: 10.4103/ijo.IJO_992_22. PMID: 35791103Free PMC Article
Maier PC, Reinhard T
Klin Monbl Augenheilkd 2022 Jun;239(6):767-774. Epub 2022 Apr 14 doi: 10.1055/a-1756-5199. PMID: 35426114
Afshari NA, Igo RP Jr, Morris NJ, Stambolian D, Sharma S, Pulagam VL, Dunn S, Stamler JF, Truitt BJ, Rimmler J, Kuot A, Croasdale CR, Qin X, Burdon KP, Riazuddin SA, Mills R, Klebe S, Minear MA, Zhao J, Balajonda E, Rosenwasser GO, Baratz KH, Mootha VV, Patel SV, Gregory SG, Bailey-Wilson JE, Price MO, Price FW Jr, Craig JE, Fingert JH, Gottsch JD, Aldave AJ, Klintworth GK, Lass JH, Li YJ, Iyengar SK
Nat Commun 2017 Mar 30;8:14898. doi: 10.1038/ncomms14898. PMID: 28358029Free PMC Article
Kreps EO, Derveaux T, De Keyser F, Kestelyn P
Ocul Immunol Inflamm 2016 Jun;24(3):348-57. Epub 2015 Jul 29 doi: 10.3109/09273948.2015.1005239. PMID: 26222767
Aldave AJ, Han J, Frausto RF
Clin Genet 2013 Aug;84(2):109-19. Epub 2013 Jun 10 doi: 10.1111/cge.12191. PMID: 23662738Free PMC Article

Therapy

Maier AB, Pilger D, Gundlach E, Winterhalter S, Torun N, Dietrich-Ntoukas T
Graefes Arch Clin Exp Ophthalmol 2023 Feb;261(2):467-476. Epub 2022 Aug 30 doi: 10.1007/s00417-022-05813-4. PMID: 36040539Free PMC Article
Jad A, Céline T, Bahram B, Phuc L, Nathalie C
Int Ophthalmol 2013 Apr;33(2):189-94. Epub 2012 Oct 16 doi: 10.1007/s10792-012-9649-7. PMID: 23070707
Sharma N, Sachdev R, Pandey RM, Titiyal JS, Sinha R, Tandon R, Vajpayee RB
Int Ophthalmol 2012 Aug;32(4):313-9. Epub 2012 Jun 3 doi: 10.1007/s10792-012-9521-9. PMID: 22661049

Prognosis

Brandi-Dohrn F, Jiang J, Grewing V, Fritz M, Zander D, Lieberum JL, Kladny AM, Siegel H, Bixler S, Müller C, Reinhard T, Wacker K
Cornea 2024 Jan 1;43(1):83-87. Epub 2023 May 8 doi: 10.1097/ICO.0000000000003291. PMID: 37157119
Kaufman AR, Bal S, Boakye J, Jurkunas UV
Cornea 2023 Aug 1;42(8):1037-1040. Epub 2022 Dec 19 doi: 10.1097/ICO.0000000000003221. PMID: 36729028
Maier PC, Reinhard T
Klin Monbl Augenheilkd 2022 Jun;239(6):767-774. Epub 2022 Apr 14 doi: 10.1055/a-1756-5199. PMID: 35426114
Perone JM, Goetz C, Zevering Y, Derumigny A, Bloch F, Vermion JC, Lhuillier L
Cornea 2022 Nov 1;41(11):1362-1371. Epub 2021 Oct 22 doi: 10.1097/ICO.0000000000002872. PMID: 34690269
Zander D, Grewing V, Glatz A, Lapp T, Maier PC, Reinhard T, Wacker K
JAMA Ophthalmol 2021 Apr 1;139(4):423-430. doi: 10.1001/jamaophthalmol.2020.6994. PMID: 33599696Free PMC Article

Clinical prediction guides

Bhadra P, Sahoo S, Sahu SK, Priyadarshini S, Mohanty A, Das S
Indian J Ophthalmol 2023 Feb;71(2):505-509. doi: 10.4103/ijo.IJO_1288_22. PMID: 36727349Free PMC Article
Arsiwalla T, Trinh T, Goolam S, Benito-Pascual B, Devasahayam RN, Moloney G
Cornea 2022 Aug 1;41(8):1064-1067. Epub 2021 Oct 20 doi: 10.1097/ICO.0000000000002873. PMID: 35830584
Zander D, Grewing V, Glatz A, Lapp T, Maier PC, Reinhard T, Wacker K
JAMA Ophthalmol 2021 Apr 1;139(4):423-430. doi: 10.1001/jamaophthalmol.2020.6994. PMID: 33599696Free PMC Article
Castellucci M, Novara C, Casuccio A, Cillino G, Giordano C, Failla V, Bonfiglio V, Vadalà M, Cillino S
Medicina (Kaunas) 2021 Feb 3;57(2) doi: 10.3390/medicina57020133. PMID: 33546152Free PMC Article
Afshari NA, Igo RP Jr, Morris NJ, Stambolian D, Sharma S, Pulagam VL, Dunn S, Stamler JF, Truitt BJ, Rimmler J, Kuot A, Croasdale CR, Qin X, Burdon KP, Riazuddin SA, Mills R, Klebe S, Minear MA, Zhao J, Balajonda E, Rosenwasser GO, Baratz KH, Mootha VV, Patel SV, Gregory SG, Bailey-Wilson JE, Price MO, Price FW Jr, Craig JE, Fingert JH, Gottsch JD, Aldave AJ, Klintworth GK, Lass JH, Li YJ, Iyengar SK
Nat Commun 2017 Mar 30;8:14898. doi: 10.1038/ncomms14898. PMID: 28358029Free PMC Article

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