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Autosomal dominant vitreoretinochoroidopathy(ADVIRC; VRCP)

MedGen UID:
854768
Concept ID:
C3888099
Disease or Syndrome
Synonyms: Vitreoretinochoroidopathy; Vitreoretinochoroidopathy dominant; VITREORETINOCHOROIDOPATHY WITH MICROCORNEA, GLAUCOMA, AND CATARACT; VITREORETINOCHOROIDOPATHY, AUTOSOMAL DOMINANT, WITH NANOPHTHALMOS; VRCP autosomal dominant
SNOMED CT: Autosomal dominant vitreoretinochoroidopathy (711162004); Vitreoretinochoroidopathy with microcornea, glaucoma and cataract (711162004); Autosomal dominant vitreoretinochoroidopathy with nanophthalmos (711162004)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): BEST1 (11q12.3)
 
Monarch Initiative: MONDO:0008662
OMIM®: 193220
Orphanet: ORPHA3086

Disease characteristics

Excerpted from the GeneReview: Bestrophinopathies
Bestrophinopathies, the spectrum of ophthalmic disorders caused by pathogenic variants in BEST1, are typically characterized by retinal degeneration. The four recognized phenotypes are the three autosomal dominant disorders: Best vitelliform macular dystrophy (BVMD), BEST1 adult-onset vitelliform macular dystrophy (AVMD), and autosomal dominant vitreoretinochoroidopathy (ADVIRC); and autosomal recessive bestrophinopathy (ARB). Onset is usually in the first decade (except AVMD in which onset is age 30 to 50 years). Slow visual deterioration is the usual course. Choroidal neovascularization can occur in rare cases. ADVIRC is also associated with panophthalmic involvement including nanophthalmos, microcornea, hyperopia, and narrow anterior chamber angle with angle closure glaucoma. [from GeneReviews]
Authors:
Ian M MacDonald  |  Thomas Lee  |  Jessica Lawrence   view full author information

Additional description

From MedlinePlus Genetics
Autosomal dominant vitreoretinochoroidopathy (ADVIRC) is a disorder that affects several parts of the eyes, including the clear gel that fills the eye (the vitreous), the light-sensitive tissue that lines the back of the eye (the retina), and the network of blood vessels within the retina (the choroid). The eye abnormalities in ADVIRC can lead to varying degrees of vision impairment, from mild reduction to complete loss, although some people with the condition have normal vision.

The signs and symptoms of ADVIRC vary, even among members of the same family. Many affected individuals have microcornea, in which the clear front covering of the eye (cornea) is small and abnormally curved. The area behind the cornea can also be abnormally small, which is described as a shallow anterior chamber. Individuals with ADVIRC can develop increased pressure in the eyes (glaucoma) or clouding of the lens of the eye (cataract). In addition, some people have breakdown (degeneration) of the vitreous or the choroid.

A characteristic feature of ADVIRC, visible with a special eye exam, is a circular band of excess coloring (hyperpigmentation) in the retina. This feature can help physicians diagnose the disorder. Affected individuals may also have white spots on the retina.  https://medlineplus.gov/genetics/condition/autosomal-dominant-vitreoretinochoroidopathy

Clinical features

From HPO
Retinal arteriolar constriction
MedGen UID:
853673
Concept ID:
C2176208
Finding
Decreased retinal arteriolar diameters, which may decrease blood flow and slow oxygen delivery to regions of the retina.
Retinal arteriolar occlusion
MedGen UID:
870318
Concept ID:
C4024761
Finding
Blockage of retinal arteriole, generally associated with interruption of blood flow and oxygen delivery to affected regions of the retina.
Developmental cataract
MedGen UID:
3202
Concept ID:
C0009691
Congenital Abnormality
A cataract that occurs congenitally as the result of a developmental defect, in contrast to the majority of cataracts that occur in adulthood as the result of degenerative changes of the lens.
Glaucoma
MedGen UID:
42224
Concept ID:
C0017601
Disease or Syndrome
Glaucoma refers loss of retinal ganglion cells in a characteristic pattern of optic neuropathy usually associated with increased intraocular pressure.
Microphthalmia
MedGen UID:
10033
Concept ID:
C0026010
Congenital Abnormality
Microphthalmia is an eye abnormality that arises before birth. In this condition, one or both eyeballs are abnormally small. In some affected individuals, the eyeball may appear to be completely missing; however, even in these cases some remaining eye tissue is generally present. Such severe microphthalmia should be distinguished from another condition called anophthalmia, in which no eyeball forms at all. However, the terms anophthalmia and severe microphthalmia are often used interchangeably. Microphthalmia may or may not result in significant vision loss.\n\nPeople with microphthalmia may also have a condition called coloboma. Colobomas are missing pieces of tissue in structures that form the eye. They may appear as notches or gaps in the colored part of the eye called the iris; the retina, which is the specialized light-sensitive tissue that lines the back of the eye; the blood vessel layer under the retina called the choroid; or in the optic nerves, which carry information from the eyes to the brain. Colobomas may be present in one or both eyes and, depending on their size and location, can affect a person's vision.\n\nPeople with microphthalmia may also have other eye abnormalities, including clouding of the lens of the eye (cataract) and a narrowed opening of the eye (narrowed palpebral fissure). Additionally, affected individuals may have an abnormality called microcornea, in which the clear front covering of the eye (cornea) is small and abnormally curved.\n\nBetween one-third and one-half of affected individuals have microphthalmia as part of a syndrome that affects other organs and tissues in the body. These forms of the condition are described as syndromic. When microphthalmia occurs by itself, it is described as nonsyndromic or isolated.
Night blindness
MedGen UID:
10349
Concept ID:
C0028077
Disease or Syndrome
Inability to see well at night or in poor 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.
Retinal detachment
MedGen UID:
19759
Concept ID:
C0035305
Disease or Syndrome
Primary or spontaneous detachment of the retina occurs due to underlying ocular disease and often involves the vitreous as well as the retina. The precipitating event is formation of a retinal tear or hole, which permits fluid to accumulate under the sensory layers of the retina and creates an intraretinal cleavage that destroys the neurosensory process of visual reception. Vitreoretinal degeneration and tear formation are painless phenomena, and in most cases, significant vitreoretinal pathology is found only after detachment of the retina starts to cause loss of vision or visual field. Without surgical intervention, retinal detachment will almost inevitably lead to total blindness (summary by McNiel and McPherson, 1971).
Retinal neovascularization
MedGen UID:
20550
Concept ID:
C0035320
Pathologic Function
In wound repair, neovascularization (NV) involves the sprouting of new vessels from pre-existent vessels to repair or replace damaged vessels. In the retina, NV is a response to ischemia. The NV adheres to the inner surface of the retina and outer surface of the vitreous. NV are deficient in tight junctions and hence leak plasma into surrounding tissue including the vitreous. Plasma causes the vitreous gel to degenerate, contract, and eventually collapse which pulls on the retina. Since retinal NV is adherent to both retina and vitreous, as the vitreous contracts the NV may be sheared resulting in vitreous hemorrhage or the NV may remain intact and pull the retina with the vitreous resulting in retinal elevation referred to as traction retinal detachment.
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.
Vitreous hemorrhage
MedGen UID:
12119
Concept ID:
C0042909
Pathologic Function
Bleeding within the vitreous compartment of the eye.
Staphyloma posticum
MedGen UID:
509934
Concept ID:
C0155360
Disease or Syndrome
A localized defect in the posterior eye wall with protrusion of uveal tissue due to alterations in scleral thickness and structure.
Color vision defect
MedGen UID:
115964
Concept ID:
C0234629
Finding
An anomaly in the ability to discriminate between or recognize colors.
Microcornea
MedGen UID:
78610
Concept ID:
C0266544
Congenital Abnormality
A congenital abnormality of the cornea in which the cornea and the anterior segment of the eye are smaller than normal. The horizontal diameter of the cornea does not reach 10 mm even in adulthood.
Blindness
MedGen UID:
99138
Concept ID:
C0456909
Disease or Syndrome
Blindness is the condition of lacking visual perception defined as a profound reduction in visual perception. On the 6m visual acuity scale, blindness is defined as less than 3/60. On the 20ft visual acuity scale, blindness is defined as less than 20/400. On the decimal visual acuity scale, blindness is defined as less than 0.05. Blindness is typically characterized by a visual field of no greater than 10 degrees in radius around central fixation.
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.
Pulverulent cataract
MedGen UID:
318793
Concept ID:
C1833118
Congenital Abnormality
A kind of congenital cataract that is characterized by a hollow sphere of punctate opacities involving the fetal nucleus and that usually occurs bilaterally.
Abnormality of chorioretinal pigmentation
MedGen UID:
870374
Concept ID:
C4024819
Finding
Pigmentary retinopathy
MedGen UID:
1643295
Concept ID:
C4551715
Disease or Syndrome
An abnormality of the retina characterized by pigment deposition. It is typically associated with migration and proliferation of macrophages or retinal pigment epithelial cells into the retina; melanin from these cells causes the pigmentary changes. Pigmentary retinopathy is a common final pathway of many retinal conditions and is often associated with visual loss.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVAutosomal dominant vitreoretinochoroidopathy

Professional guidelines

Curated

Ramsden SC, Davidson AE, Leroy BP, Moore AT, Webster AR, Black GC, Manson FD
Eur J Hum Genet 2012 May;20(5) Epub 2012 Jan 11 doi: 10.1038/ejhg.2011.251. PMID: 22234150Free PMC Article

Recent clinical studies

Etiology

Boulanger-Scemama E, Sahel JA, Mohand-Said S, Antonio A, Condroyer C, Zeitz C, Audo I
Retina 2019 May;39(5):867-878. doi: 10.1097/IAE.0000000000002041. PMID: 29370033
Chen CJ, Kaufman S, Packo K, Stöhr H, Weber BH, Goldberg MF
Ophthalmic Genet 2016;37(1):102-8. Epub 2016 Feb 5 doi: 10.3109/13816810.2015.1039893. PMID: 26849243
Kellner S, Stöhr H, Fiebig B, Weinitz S, Farmand G, Kellner U, Weber BH
Ophthalmic Genet 2016 Jun;37(2):201-8. Epub 2016 Jan 15 doi: 10.3109/13816810.2015.1033556. PMID: 26771239
Vincent A, McAlister C, Vandenhoven C, Héon E
Eye (Lond) 2011 Jan;25(1):113-8. Epub 2010 Nov 12 doi: 10.1038/eye.2010.165. PMID: 21072067Free PMC Article

Diagnosis

Boulanger-Scemama E, Sahel JA, Mohand-Said S, Antonio A, Condroyer C, Zeitz C, Audo I
Retina 2019 May;39(5):867-878. doi: 10.1097/IAE.0000000000002041. PMID: 29370033
Mano F, LoBue SA, Olsen TW, Marmorstein AD, Pulido JS
Ophthalmic Genet 2018 Dec;39(6):749-753. Epub 2018 Sep 17 doi: 10.1080/13816810.2018.1520264. PMID: 30222024
Lafaut BA, Loeys B, Leroy BP, Spileers W, De Laey JJ, Kestelyn P
Graefes Arch Clin Exp Ophthalmol 2001 Aug;239(8):575-82. doi: 10.1007/s004170100318. PMID: 11585313
Traboulsi EI, Payne JW
Arch Ophthalmol 1993 Feb;111(2):194-6. doi: 10.1001/archopht.1993.01090020048021. PMID: 8431155
Kaufman SJ, Goldberg MF, Orth DH, Fishman GA, Tessler H, Mizuno K
Arch Ophthalmol 1982 Feb;100(2):272-8. doi: 10.1001/archopht.1982.01030030274008. PMID: 7065944

Therapy

Mano F, LoBue SA, Olsen TW, Marmorstein AD, Pulido JS
Ophthalmic Genet 2018 Dec;39(6):749-753. Epub 2018 Sep 17 doi: 10.1080/13816810.2018.1520264. PMID: 30222024
Kellner S, Stöhr H, Fiebig B, Weinitz S, Farmand G, Kellner U, Weber BH
Ophthalmic Genet 2016 Jun;37(2):201-8. Epub 2016 Jan 15 doi: 10.3109/13816810.2015.1033556. PMID: 26771239

Prognosis

Boulanger-Scemama E, Sahel JA, Mohand-Said S, Antonio A, Condroyer C, Zeitz C, Audo I
Retina 2019 May;39(5):867-878. doi: 10.1097/IAE.0000000000002041. PMID: 29370033
Kellner S, Stöhr H, Fiebig B, Weinitz S, Farmand G, Kellner U, Weber BH
Ophthalmic Genet 2016 Jun;37(2):201-8. Epub 2016 Jan 15 doi: 10.3109/13816810.2015.1033556. PMID: 26771239
Vincent A, McAlister C, Vandenhoven C, Héon E
Eye (Lond) 2011 Jan;25(1):113-8. Epub 2010 Nov 12 doi: 10.1038/eye.2010.165. PMID: 21072067Free PMC Article
Edwards AO
Eye (Lond) 2008 Oct;22(10):1233-42. Epub 2008 Feb 29 doi: 10.1038/eye.2008.38. PMID: 18309337
Traboulsi EI, Payne JW
Arch Ophthalmol 1993 Feb;111(2):194-6. doi: 10.1001/archopht.1993.01090020048021. PMID: 8431155

Clinical prediction guides

Mano F, LoBue SA, Olsen TW, Marmorstein AD, Pulido JS
Ophthalmic Genet 2018 Dec;39(6):749-753. Epub 2018 Sep 17 doi: 10.1080/13816810.2018.1520264. PMID: 30222024
Chen CJ, Kaufman S, Packo K, Stöhr H, Weber BH, Goldberg MF
Ophthalmic Genet 2016;37(1):102-8. Epub 2016 Feb 5 doi: 10.3109/13816810.2015.1039893. PMID: 26849243
Vincent A, McAlister C, Vandenhoven C, Héon E
Eye (Lond) 2011 Jan;25(1):113-8. Epub 2010 Nov 12 doi: 10.1038/eye.2010.165. PMID: 21072067Free PMC Article
Boon CJ, Klevering BJ, Leroy BP, Hoyng CB, Keunen JE, den Hollander AI
Prog Retin Eye Res 2009 May;28(3):187-205. Epub 2009 Apr 16 doi: 10.1016/j.preteyeres.2009.04.002. PMID: 19375515

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