RVCL
MCID: VSC016
MIFTS: 40

Vasculopathy, Retinal, with Cerebral Leukodystrophy (RVCL)

Categories: Genetic diseases, Rare diseases

Aliases & Classifications for Vasculopathy, Retinal, with Cerebral Leukodystrophy

MalaCards integrated aliases for Vasculopathy, Retinal, with Cerebral Leukodystrophy:

Name: Vasculopathy, Retinal, with Cerebral Leukodystrophy 58 76 30 13 6 41 74
Rvcl 58 54 76
Crv 58 54 76
Retinopathy, Vascular, with Cerebral and Renal Involvement and Raynaud and Migraine Phenomena 58 54
Retinal Vasculopathy with Cerebral Leukodystrophy 54 38
Cerebroretinal Vasculopathy, Hereditary 58 54
Vascular Retinopathy with Cerebral and Renal Involvement and Raynaud and Migraine Phenomena 76
Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic Manifestations 54
Autosomal Dominant Retinal Vasculopathy with Cerebral Leukodystrophy 54
Hereditary Endotheliopathy with Retinopathy-Nephropathy-Stroke 76
Retinal Vasculopathy and Cerebral Leukoencephalopathy 54
Cerebroretinal Vasculopathy, Hereditary; Crv 58
Cerebroretinal Vasculopathy 76
Rvcl-S 54
Adrvcl 54
Herns 76

Characteristics:

OMIM:

58
Inheritance:
autosomal dominant

Miscellaneous:
progressive disorder
onset in adulthood
death occurs 5 to 10 years after onset


HPO:

33
vasculopathy, retinal, with cerebral leukodystrophy:
Onset and clinical course adult onset progressive
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Vasculopathy, Retinal, with Cerebral Leukodystrophy

NIH Rare Diseases : 54 Retinal vasculopathy with cerebral leukodystrophy (RVCL) is a rare, genetic condition that primarily affects the central nervous system. Symptoms begin in adulthood (usually in the 40s) and may include loss of vision, mini-strokes, and dementia. Death can sometimes occur within 10 years of the first symptoms appearing. RVCL is inherited in an autosomal dominant manner and is caused by mutations in the TREX1 gene. Treatments currently aim to manage or alleviate the symptoms rather than treating the underlying cause.RVCL is now considered to include the following 3 conditions which were previously thought to be distinct: hereditary endotheliopathy, retinopathy, nephropathy, and stroke (HERNS); cerebroretinal vasculopathy (CRV); and hereditary vascular retinopathy (HVR).

MalaCards based summary : Vasculopathy, Retinal, with Cerebral Leukodystrophy, also known as rvcl, is related to hereditary endotheliopathy, retinopathy, nephropathy, and stroke and leukodystrophy, and has symptoms including seizures and hemiparesis. An important gene associated with Vasculopathy, Retinal, with Cerebral Leukodystrophy is TREX1 (Three Prime Repair Exonuclease 1), and among its related pathways/superpathways are Cytosolic DNA-sensing pathway and Chks in Checkpoint Regulation. The drugs Aclarubicin and Anti-Bacterial Agents have been mentioned in the context of this disorder. Affiliated tissues include brain, retina and skin, and related phenotypes are leukodystrophy and focal white matter lesions

OMIM : 58 Retinal vasculopathy with cerebral leukodystrophy is an adult-onset autosomal dominant disorder involving the microvessels of the brain and resulting in central nervous system degeneration with progressive loss of vision, stroke, motor impairment, and cognitive decline. Death occurs in most patients 5 to 10 years after onset. A subset of affected individuals have systemic vascular involvement evidenced by Raynaud's phenomenon, micronodular cirrhosis, and glomerular dysfunction (summary by Richards et al., 2007). (192315)

UniProtKB/Swiss-Prot : 76 Vasculopathy, retinal, with cerebral leukodystrophy: A microvascular endotheliopathy resulting in central nervous system degeneration and retinopathy, with progressive loss of vision, stroke, motor impairment, and cognitive decline. The ocular manifestations are characterized by telangiectasias, microaneurysms and retinal capillary obliteration starting in the macula. Diseased cerebral white matter has prominent small infarcts that often coalesce to pseudotumors.

Wikipedia : 77 Autosomal Dominant Retinal Vasculopathy with Cerebral Leukodystrophy (AD-RVCL) (previously known also as... more...

Related Diseases for Vasculopathy, Retinal, with Cerebral Leukodystrophy

Diseases related to Vasculopathy, Retinal, with Cerebral Leukodystrophy via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 hereditary endotheliopathy, retinopathy, nephropathy, and stroke 11.5
2 leukodystrophy 10.5
3 inguinal hernia 10.3
4 multiple sclerosis 10.3
5 cutaneous collagenous vasculopathy 10.2
6 hereditary vascular retinopathy 10.2
7 cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1 10.1
8 aicardi-goutieres syndrome 1 9.7 SHISA5 TREX1
9 aicardi-goutieres syndrome 9.3 ATRIP SHISA5 TREX1

Graphical network of the top 20 diseases related to Vasculopathy, Retinal, with Cerebral Leukodystrophy:



Diseases related to Vasculopathy, Retinal, with Cerebral Leukodystrophy

Symptoms & Phenotypes for Vasculopathy, Retinal, with Cerebral Leukodystrophy

Human phenotypes related to Vasculopathy, Retinal, with Cerebral Leukodystrophy:

33 (show all 37)
# Description HPO Frequency HPO Source Accession
1 leukodystrophy 33 hallmark (90%) HP:0002415
2 focal white matter lesions 33 hallmark (90%) HP:0007042
3 seizures 33 frequent (33%) HP:0001250
4 dysarthria 33 frequent (33%) HP:0001260
5 behavioral abnormality 33 frequent (33%) HP:0000708
6 retinopathy 33 frequent (33%) HP:0000488
7 progressive visual loss 33 frequent (33%) HP:0000529
8 migraine 33 frequent (33%) HP:0002076
9 apraxia 33 frequent (33%) HP:0002186
10 mental deterioration 33 frequent (33%) HP:0001268
11 stroke 33 frequent (33%) HP:0001297
12 hemiparesis 33 frequent (33%) HP:0001269
13 abnormal retinal vascular morphology 33 frequent (33%) HP:0008046
14 ataxia 33 occasional (7.5%) HP:0001251
15 proteinuria 33 occasional (7.5%) HP:0000093
16 nephropathy 33 occasional (7.5%) HP:0000112
17 glomerulopathy 33 occasional (7.5%) HP:0100820
18 hematuria 33 occasional (7.5%) HP:0000790
19 sensory impairment 33 occasional (7.5%) HP:0003474
20 micronodular cirrhosis 33 occasional (7.5%) HP:0001413
21 visual impairment 33 HP:0000505
22 elevated hepatic transaminase 33 HP:0002910
23 dementia 33 HP:0000726
24 lower limb hyperreflexia 33 HP:0002395
25 central nervous system degeneration 33 HP:0007009
26 retinal hemorrhage 33 HP:0000573
27 abnormality of the periventricular white matter 33 HP:0002518
28 raynaud phenomenon 33 HP:0030880
29 elevated erythrocyte sedimentation rate 33 HP:0003565
30 telangiectasia 33 HP:0001009
31 retinal exudate 33 HP:0001147
32 macular edema 33 HP:0040049
33 vasculitis in the skin 33 HP:0200029
34 progressive forgetfulness 33 HP:0007017
35 limb pain 33 HP:0009763
36 punctate vasculitis skin lesions 33 HP:0200030
37 diminished ability to concentrate 33 HP:0031987

Symptoms via clinical synopsis from OMIM:

58
Neurologic Central Nervous System:
seizures
dysarthria
migraine
apraxia
stroke
more
Head And Neck Eyes:
retinal hemorrhage
macular edema
retinal exudates
retinal vasculopathy
decreased visual acuity, progressive
more
Abdomen Liver:
micronodular cirrhosis (less common)

Skin Nails Hair Skin:
punctate vasculitis skin lesions

Laboratory Abnormalities:
proteinuria
hematuria
abnormal liver enzymes

Cardiovascular Vascular:
raynaud phenomenon

Genitourinary Kidneys:
glomerular dysfunction (variable)

Neurologic Behavioral Psychiatric Manifestations:
psychiatric disturbances

Clinical features from OMIM:

192315

UMLS symptoms related to Vasculopathy, Retinal, with Cerebral Leukodystrophy:


seizures, hemiparesis

Drugs & Therapeutics for Vasculopathy, Retinal, with Cerebral Leukodystrophy

Drugs for Vasculopathy, Retinal, with Cerebral Leukodystrophy (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 7)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Aclarubicin Investigational Phase 1 57576-44-0 451415
2 Anti-Bacterial Agents Phase 1
3 Immunologic Factors Phase 1
4 Adjuvants, Immunologic Phase 1
5 Aclacinomycins Phase 1
6 Topoisomerase Inhibitors Phase 1
7 Antibiotics, Antitubercular Phase 1

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Aclarubicin for the Treatment of Retinal Vasculopathy With Cerebral Leukodystrophy Active, not recruiting NCT02723448 Phase 1 aclarubicin

Search NIH Clinical Center for Vasculopathy, Retinal, with Cerebral Leukodystrophy

Genetic Tests for Vasculopathy, Retinal, with Cerebral Leukodystrophy

Genetic tests related to Vasculopathy, Retinal, with Cerebral Leukodystrophy:

# Genetic test Affiliating Genes
1 Vasculopathy, Retinal, with Cerebral Leukodystrophy 30 TREX1

Anatomical Context for Vasculopathy, Retinal, with Cerebral Leukodystrophy

MalaCards organs/tissues related to Vasculopathy, Retinal, with Cerebral Leukodystrophy:

42
Brain, Retina, Skin

Publications for Vasculopathy, Retinal, with Cerebral Leukodystrophy

Articles related to Vasculopathy, Retinal, with Cerebral Leukodystrophy:

(show all 15)
# Title Authors Year
1
In Reply to 'TREX1 Mutation Causing Autosomal Dominant Thrombotic Microangiopathy and CKD Is in Fact a Case of RVCL-S Presenting With Renal Features'. ( 30846257 )
2019
2
TREX1 Mutation Causing Autosomal Dominant Thrombotic Microangiopathy and CKD Is in Fact a Case of RVCL-S Presenting With Renal Features. ( 30846258 )
2019
3
Retinal Vasculopathy With Cerebral Leukodystrophy: Clinicopathologic Features of an Autopsied Patient With a Heterozygous TREX 1 Mutation. ( 30561700 )
2018
4
Renal histopathological findings of retinal vasculopathy with cerebral leukodystrophy. ( 29322432 )
2018
5
Phenotypic Variability in a Mexican Mestizo Family with Retinal Vasculopathy with Cerebral Leukodystrophy and TREX1 Mutation p.V235Gfs*6. ( 29718010 )
2018
6
RVCL-S and CADASIL display distinct impaired vascular function. ( 30076273 )
2018
7
Retinal vasculopathy with cerebral leukoencephalopathy (RVCL): A rare mimic of tumefactive MS. ( 30194247 )
2018
8
Tumefactive lesions in retinal vasculopathy with cerebral leucoencephalopathy and systemic manifestations (RVCL-S): a role for neuroinflammation? ( 28794152 )
2017
9
TREX1 C-terminal frameshift mutations in the systemic variant of retinal vasculopathy with cerebral leukodystrophy. ( 25213617 )
2015
10
Multiple sclerosis-like lesions and type I interferon signature in a patient with RVCL. ( 25566545 )
2015
11
Novel ophthalmic pathology in an autopsy case of autosomal dominant retinal vasculopathy with cerebral leukodystrophy. ( 21131853 )
2011
12
C-terminal truncations in human 3'-5' DNA exonuclease TREX1 cause autosomal dominant retinal vasculopathy with cerebral leukodystrophy. ( 17660820 )
2007
13
Hereditary endotheliopathy with retinopathy, nephropathy, and stroke (HERNS). ( 9371916 )
1997
14
A new autosomal dominant vascular retinopathy syndrome. ( 1821204 )
1991
15
Cerebroretinal vasculopathy. A new hereditary syndrome. ( 3174024 )
1988

Variations for Vasculopathy, Retinal, with Cerebral Leukodystrophy

ClinVar genetic disease variations for Vasculopathy, Retinal, with Cerebral Leukodystrophy:

6 (show top 50) (show all 81)
# Gene Variation Type Significance SNP ID Assembly Location
1 TREX1 NM_033629.2(TREX1): c.341G> A (p.Arg114His) single nucleotide variant risk factor rs72556554 GRCh37 Chromosome 3, 48508395: 48508395
2 TREX1 NM_033629.2(TREX1): c.341G> A (p.Arg114His) single nucleotide variant risk factor rs72556554 GRCh38 Chromosome 3, 48466996: 48466996
3 TREX1 TREX1, 1-BP INS, 3688G insertion Pathogenic
4 TREX1 NM_033629.5(TREX1): c.703_706dup (p.Thr236Serfs) duplication Pathogenic GRCh38 Chromosome 3, 48467358: 48467361
5 TREX1 NM_033629.5(TREX1): c.703_706dup (p.Thr236Serfs) duplication Pathogenic GRCh37 Chromosome 3, 48508757: 48508760
6 TREX1 NM_033629.5(TREX1): c.531T= (p.Tyr177=) single nucleotide variant Benign rs11797 GRCh37 Chromosome 3, 48508585: 48508585
7 TREX1 NM_033629.5(TREX1): c.531T= (p.Tyr177=) single nucleotide variant Benign rs11797 GRCh38 Chromosome 3, 48467186: 48467186
8 TREX1 NM_033629.5(TREX1): c.797A> G (p.Glu266Gly) single nucleotide variant Conflicting interpretations of pathogenicity rs55999987 GRCh37 Chromosome 3, 48508851: 48508851
9 TREX1 NM_033629.5(TREX1): c.797A> G (p.Glu266Gly) single nucleotide variant Conflicting interpretations of pathogenicity rs55999987 GRCh38 Chromosome 3, 48467452: 48467452
10 TREX1 NM_033629.4(TREX1): c.907A> C (p.Thr303Pro) single nucleotide variant Uncertain significance rs76224909 GRCh37 Chromosome 3, 48508961: 48508961
11 TREX1 NM_033629.4(TREX1): c.907A> C (p.Thr303Pro) single nucleotide variant Uncertain significance rs76224909 GRCh38 Chromosome 3, 48467562: 48467562
12 TREX1 NM_033629.4(TREX1): c.340C> T (p.Arg114Cys) single nucleotide variant Likely pathogenic rs760838030 GRCh37 Chromosome 3, 48508394: 48508394
13 TREX1 NM_033629.4(TREX1): c.340C> T (p.Arg114Cys) single nucleotide variant Likely pathogenic rs760838030 GRCh38 Chromosome 3, 48466995: 48466995
14 TREX1 NM_033629.4(TREX1): c.912G> A (p.Leu304=) single nucleotide variant Benign rs3135945 GRCh38 Chromosome 3, 48467567: 48467567
15 TREX1 NM_033629.4(TREX1): c.912G> A (p.Leu304=) single nucleotide variant Benign rs3135945 GRCh37 Chromosome 3, 48508966: 48508966
16 TREX1 NM_033629.5(TREX1): c.-515T> C single nucleotide variant Likely benign rs148393533 GRCh38 Chromosome 3, 48465821: 48465821
17 TREX1 NM_033629.5(TREX1): c.-515T> C single nucleotide variant Likely benign rs148393533 GRCh37 Chromosome 3, 48507220: 48507220
18 TREX1 NM_033629.4(TREX1): c.-510delC deletion Likely benign rs3135939 GRCh38 Chromosome 3, 48465826: 48465826
19 TREX1 NM_033629.4(TREX1): c.-510delC deletion Likely benign rs3135939 GRCh37 Chromosome 3, 48507225: 48507225
20 TREX1 NM_033629.5(TREX1): c.-100C> T single nucleotide variant Uncertain significance rs886058623 GRCh38 Chromosome 3, 48466236: 48466236
21 TREX1 NM_033629.5(TREX1): c.-100C> T single nucleotide variant Uncertain significance rs886058623 GRCh37 Chromosome 3, 48507635: 48507635
22 TREX1 NM_033629.5(TREX1): c.-60C> T single nucleotide variant Likely benign rs2279076 GRCh38 Chromosome 3, 48466276: 48466276
23 TREX1 NM_033629.5(TREX1): c.-60C> T single nucleotide variant Likely benign rs2279076 GRCh37 Chromosome 3, 48507675: 48507675
24 TREX1 NM_033629.5(TREX1): c.9G> A (p.Ser3=) single nucleotide variant Uncertain significance rs762687506 GRCh38 Chromosome 3, 48466664: 48466664
25 TREX1 NM_033629.5(TREX1): c.9G> A (p.Ser3=) single nucleotide variant Uncertain significance rs762687506 GRCh37 Chromosome 3, 48508063: 48508063
26 TREX1 NM_033629.4(TREX1): c.198G> A (p.Lys66=) single nucleotide variant Benign/Likely benign rs3135943 GRCh38 Chromosome 3, 48466853: 48466853
27 TREX1 NM_033629.4(TREX1): c.198G> A (p.Lys66=) single nucleotide variant Benign/Likely benign rs3135943 GRCh37 Chromosome 3, 48508252: 48508252
28 TREX1 NM_033629.5(TREX1): c.418A> G (p.Met140Val) single nucleotide variant Uncertain significance rs761526437 GRCh38 Chromosome 3, 48467073: 48467073
29 TREX1 NM_033629.5(TREX1): c.418A> G (p.Met140Val) single nucleotide variant Uncertain significance rs761526437 GRCh37 Chromosome 3, 48508472: 48508472
30 TREX1 NM_033629.5(TREX1): c.-199A> G single nucleotide variant Uncertain significance rs767364235 GRCh38 Chromosome 3, 48466137: 48466137
31 TREX1 NM_033629.5(TREX1): c.-199A> G single nucleotide variant Uncertain significance rs767364235 GRCh37 Chromosome 3, 48507536: 48507536
32 TREX1 NM_033629.5(TREX1): c.-68T> C single nucleotide variant Benign rs3135941 GRCh38 Chromosome 3, 48466268: 48466268
33 TREX1 NM_033629.5(TREX1): c.-68T> C single nucleotide variant Benign rs3135941 GRCh37 Chromosome 3, 48507667: 48507667
34 TREX1 NM_033629.5(TREX1): c.183G> A (p.Pro61=) single nucleotide variant Likely benign rs55852466 GRCh38 Chromosome 3, 48466838: 48466838
35 TREX1 NM_033629.5(TREX1): c.183G> A (p.Pro61=) single nucleotide variant Likely benign rs55852466 GRCh37 Chromosome 3, 48508237: 48508237
36 TREX1 NM_033629.5(TREX1): c.312G> C (p.Leu104=) single nucleotide variant Uncertain significance rs56162833 GRCh38 Chromosome 3, 48466967: 48466967
37 TREX1 NM_033629.5(TREX1): c.312G> C (p.Leu104=) single nucleotide variant Uncertain significance rs56162833 GRCh37 Chromosome 3, 48508366: 48508366
38 TREX1 NM_033629.5(TREX1): c.*37T> C single nucleotide variant Benign rs3135946 GRCh38 Chromosome 3, 48467637: 48467637
39 TREX1 NM_033629.5(TREX1): c.*37T> C single nucleotide variant Benign rs3135946 GRCh37 Chromosome 3, 48509036: 48509036
40 TREX1 NM_033629.5(TREX1): c.-127G> C single nucleotide variant Uncertain significance rs577465983 GRCh38 Chromosome 3, 48466209: 48466209
41 TREX1 NM_033629.5(TREX1): c.-127G> C single nucleotide variant Uncertain significance rs577465983 GRCh37 Chromosome 3, 48507608: 48507608
42 TREX1 NM_033629.5(TREX1): c.394C> G (p.Pro132Ala) single nucleotide variant Likely benign rs200510205 GRCh38 Chromosome 3, 48467049: 48467049
43 TREX1 NM_033629.5(TREX1): c.394C> G (p.Pro132Ala) single nucleotide variant Likely benign rs200510205 GRCh37 Chromosome 3, 48508448: 48508448
44 TREX1 NM_033629.4(TREX1): c.462T> C (p.Asp154=) single nucleotide variant Benign/Likely benign rs3135944 GRCh38 Chromosome 3, 48467117: 48467117
45 TREX1 NM_033629.4(TREX1): c.462T> C (p.Asp154=) single nucleotide variant Benign/Likely benign rs3135944 GRCh37 Chromosome 3, 48508516: 48508516
46 TREX1 NM_033629.5(TREX1): c.536T> C (p.Leu179Pro) single nucleotide variant Uncertain significance rs886058625 GRCh38 Chromosome 3, 48467191: 48467191
47 TREX1 NM_033629.5(TREX1): c.536T> C (p.Leu179Pro) single nucleotide variant Uncertain significance rs886058625 GRCh37 Chromosome 3, 48508590: 48508590
48 TREX1 NM_033629.5(TREX1): c.-287C> T single nucleotide variant Uncertain significance rs377157141 GRCh38 Chromosome 3, 48466049: 48466049
49 TREX1 NM_033629.5(TREX1): c.-287C> T single nucleotide variant Uncertain significance rs377157141 GRCh37 Chromosome 3, 48507448: 48507448
50 TREX1 NM_033629.5(TREX1): c.-206G> T single nucleotide variant Uncertain significance rs886058622 GRCh38 Chromosome 3, 48466130: 48466130

Expression for Vasculopathy, Retinal, with Cerebral Leukodystrophy

Search GEO for disease gene expression data for Vasculopathy, Retinal, with Cerebral Leukodystrophy.

Pathways for Vasculopathy, Retinal, with Cerebral Leukodystrophy

Pathways related to Vasculopathy, Retinal, with Cerebral Leukodystrophy according to KEGG:

38
# Name Kegg Source Accession
1 Cytosolic DNA-sensing pathway hsa04623

Pathways related to Vasculopathy, Retinal, with Cerebral Leukodystrophy according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.56 ATRIP TREX1
2
Show member pathways
10.99 ATRIP SHISA5

GO Terms for Vasculopathy, Retinal, with Cerebral Leukodystrophy

Cellular components related to Vasculopathy, Retinal, with Cerebral Leukodystrophy according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nuclear envelope GO:0005635 8.62 SHISA5 TREX1

Biological processes related to Vasculopathy, Retinal, with Cerebral Leukodystrophy according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 DNA repair GO:0006281 9.16 ATRIP TREX1
2 DNA replication GO:0006260 8.96 ATRIP TREX1
3 nucleic acid phosphodiester bond hydrolysis GO:0090305 8.62 ATRIP TREX1

Molecular functions related to Vasculopathy, Retinal, with Cerebral Leukodystrophy according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 exonuclease activity GO:0004527 8.62 ATRIP TREX1

Sources for Vasculopathy, Retinal, with Cerebral Leukodystrophy

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