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Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations(RVCLS)

MedGen UID:
348124
Concept ID:
C1860518
Disease or Syndrome
Synonyms: Cerebroretinal vasculopathy, hereditary; Retinopathy, vascular, with cerebral and renal involvement and Raynaud and migraine phenomena; RVCLS; Vasculopathy, retinal, with cerebral leukodystrophy
SNOMED CT: Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (783787000); RVCL - retinal vasculopathy cerebral leukoencephalopathy (783787000); RVCL-S - retinal vasculopathy, cerebral leukoencephalopathy, systemic manifestations (783787000)
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): TREX1 (3p21.31)
 
Monarch Initiative: MONDO:0008641
OMIM®: 192315
Orphanet: ORPHA247691

Disease characteristics

Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a small-vessel disease that affects highly vascularized tissues including the retina, brain, liver, and kidneys. Age of onset is often between 35 and 50 years. The most common presenting finding is decreased visual acuity and/or visual field defects. Neurologic manifestations may include hemiparesis, facial weakness, aphasia, and hemianopsia. Migraines and seizures are less frequently described. Renal manifestations may include mild-to-moderate increase in serum creatinine and mild proteinuria; progression to end-stage renal disease (ESRD) is uncommon. Hepatic manifestations frequently include mildly elevated levels of alkaline phosphatase and gamma-glutamyltransferase (GGT). Less common findings include psychiatric disorders, hypertension, mild-to-moderate anemia, and Raynaud phenomenon. [from GeneReviews]
Authors:
Irene de Boer  |  Nadine Pelzer  |  Gisela Terwindt   view full author information

Additional description

From OMIM
Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCLS) 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 phenomenon, micronodular cirrhosis, and glomerular dysfunction (summary by Richards et al., 2007).  http://www.omim.org/entry/192315

Clinical features

From HPO
Limb pain
MedGen UID:
10540
Concept ID:
C0030196
Sign or Symptom
Chronic pain in the limbs with no clear focal etiology.
Hematuria
MedGen UID:
5488
Concept ID:
C0018965
Disease or Syndrome
The presence of blood in the urine. Hematuria may be gross hematuria (visible to the naked eye) or microscopic hematuria (detected by dipstick or microscopic examination of the urine).
Proteinuria
MedGen UID:
10976
Concept ID:
C0033687
Finding
Increased levels of protein in the urine.
Raynaud phenomenon
MedGen UID:
20474
Concept ID:
C0034735
Disease or Syndrome
An episodic vasoconstriction resulting in discoloration of the skin and pain in the affected areas, often involving fingers or toes. Classically associated with triphasic color changes (white, blue, red) but may be biphasic. Often occurs in response to cold temperatures or emotional stress. May be primary or secondary to an underlying autoimmune disease.
Stroke disorder
MedGen UID:
52522
Concept ID:
C0038454
Disease or Syndrome
Sudden impairment of blood flow to a part of the brain due to occlusion or rupture of an artery to the brain.
Vasculitis in the skin
MedGen UID:
488809
Concept ID:
C0262988
Disease or Syndrome
A type of vasculitis (inflammation of blood vessel walls) that affects skeletal muscle tissue.
Punctate vasculitis skin lesions
MedGen UID:
479323
Concept ID:
C3277693
Finding
Gastrointestinal hemorrhage
MedGen UID:
8971
Concept ID:
C0017181
Pathologic Function
Hemorrhage affecting the gastrointestinal tract.
Micronodular cirrhosis
MedGen UID:
75640
Concept ID:
C0267812
Disease or Syndrome
A type of cirrhosis characterized by the presence of small regenerative nodules.
Apraxia
MedGen UID:
8166
Concept ID:
C0003635
Mental or Behavioral Dysfunction
A defect in the understanding of complex motor commands and in the execution of certain learned movements, i.e., deficits in the cognitive components of learned movements.
Atypical behavior
MedGen UID:
14048
Concept ID:
C0004941
Sign or Symptom
Atypical behavior is an abnormality in a person's actions that can be controlled or modulated by the will of the individual. While abnormal behaviors can be difficult to control, they are distinct from other abnormal actions that cannot be affected by the individual's will.
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
Hemiparesis
MedGen UID:
6783
Concept ID:
C0018989
Finding
Loss of strength in the arm, leg, and sometimes face on one side of the body. Hemiplegia refers to a complete loss of strength, whereas hemiparesis refers to an incomplete loss of strength.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Migraine
MedGen UID:
57451
Concept ID:
C0149931
Disease or Syndrome
Migraine is a chronic neurological disorder characterized by episodic attacks of headache and associated symptoms.
Diminished ability to concentrate
MedGen UID:
65900
Concept ID:
C0235198
Finding
The inability to focus or concentrate on a specific task, activity, or object. The subject may find themselves unable to grasp or understand written text and re-reads frequently without understanding. Familiar tasks or activities are severely compromised due to the lack of ability to concentrate. Thinking through multi-step problems is typically very difficult or impossible, leading to avoidance of such activities.
Dementia
MedGen UID:
99229
Concept ID:
C0497327
Mental or Behavioral Dysfunction
A loss of global cognitive ability of sufficient amount to interfere with normal social or occupational function. Dementia represents a loss of previously present cognitive abilities, generally in adults, and can affect memory, thinking, language, judgment, and behavior.
Lower limb hyperreflexia
MedGen UID:
322973
Concept ID:
C1836696
Finding
Abnormal periventricular white matter morphology
MedGen UID:
435926
Concept ID:
C2673431
Finding
A structural abnormality of the myelinated axons (white matter) located near the cerebral ventricles.
Central nervous system degeneration
MedGen UID:
479317
Concept ID:
C3277687
Finding
Progressive forgetfulness
MedGen UID:
479318
Concept ID:
C3277688
Finding
Edema
MedGen UID:
4451
Concept ID:
C0013604
Pathologic Function
An abnormal accumulation of fluid beneath the skin, or in one or more cavities of the body.
Elevated erythrocyte sedimentation rate
MedGen UID:
57727
Concept ID:
C0151632
Finding
An increased erythrocyte sedimentation rate (ESR). The ESR is a test that measures the distance that erythrocytes have fallen after one hour in a vertical column of anticoagulated blood under the influence of gravity. The ESR is a nonspecific finding. An elevation may indicate inflammation or may be caused by any condition that elevates fibrinogen.
Elevated circulating hepatic transaminase concentration
MedGen UID:
116013
Concept ID:
C0235996
Finding
Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage.
Telangiectasia
MedGen UID:
21088
Concept ID:
C0039446
Finding
Telangiectasias refer to small dilated blood vessels located near the surface of the skin or mucous membranes, measuring between 0.5 and 1 millimeter in diameter. Telangiectasia are located especially on the tongue, lips, palate, fingers, face, conjunctiva, trunk, nail beds, and fingertips.
Retinal hemorrhage
MedGen UID:
11210
Concept ID:
C0035317
Pathologic Function
Hemorrhage occurring within the retina.
Retinal exudate
MedGen UID:
116111
Concept ID:
C0240897
Finding
Fluid which has escaped from retinal blood vessels with a high concentration of lipid, protein, and cellular debris with a typically bright, reflective, white or cream colored appearance on the surface of the retina.
Macular edema
MedGen UID:
75732
Concept ID:
C0271051
Disease or Syndrome
Thickening of the retina that takes place due to accumulation of fluid in the macula as a nonspecific response to blood-retinal barrier breakdown. Macular edema is a common pathological response to a wide variety of ocular insults, most commonly after intraocular (e.g. cataract) surgery or in association with retinal vascular (e.g. diabetic eye disease, retinal vein occlusion) or inflammatory (e.g. uveitis) disease.
Progressive visual loss
MedGen UID:
326867
Concept ID:
C1839364
Finding
A reduction of previously attained ability to see.
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.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVRetinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations

Professional guidelines

PubMed

Mancuso M, Arnold M, Bersano A, Burlina A, Chabriat H, Debette S, Enzinger C, Federico A, Filla A, Finsterer J, Hunt D, Lesnik Oberstein S, Tournier-Lasserve E, Markus HS
Eur J Neurol 2020 Jun;27(6):909-927. Epub 2020 Mar 20 doi: 10.1111/ene.14183. PMID: 32196841

Recent clinical studies

Etiology

Wilms AE, de Boer I, Pelzer N, In't Veld SGJG, Middelkoop HAM, Teunissen CE, Terwindt GM
J Neurol 2024 Jul;271(7):4138-4145. Epub 2024 Apr 6 doi: 10.1007/s00415-024-12292-6. PMID: 38581544Free PMC Article
Foddis M, Blumenau S, Holtgrewe M, Paquette K, Westra K, Alonso I, Macario MDC, Morgadinho AS, Velon AG, Santo G, Santana I, Mönkäre S, Kuuluvainen L, Schleutker J, Pöyhönen M, Myllykangas L, Pavlovic A, Kostic V, Dobricic V, Lohmann E, Hanagasi H, Santos M, Guven G, Bilgic B, Bras J, Beule D, Dirnagl U, Guerreiro R, Sassi C
Neurobiol Aging 2023 Mar;123:208-215. Epub 2022 Nov 26 doi: 10.1016/j.neurobiolaging.2022.11.013. PMID: 36586737
Mancuso M, Arnold M, Bersano A, Burlina A, Chabriat H, Debette S, Enzinger C, Federico A, Filla A, Finsterer J, Hunt D, Lesnik Oberstein S, Tournier-Lasserve E, Markus HS
Eur J Neurol 2020 Jun;27(6):909-927. Epub 2020 Mar 20 doi: 10.1111/ene.14183. PMID: 32196841
Mulder IA, Rubio-Beltran E, Ibrahimi K, Dzyubachyk O, Khmelinskii A, Hoehn M, Terwindt GM, Wermer MJH, MaassenVanDenBrink A, van den Maagdenberg AMJM
Stroke 2020 Jan;51(1):300-307. Epub 2019 Dec 6 doi: 10.1161/STROKEAHA.119.025176. PMID: 31805844
Hedderich DM, Lummel N, Deschauer M, Kümpfel T, Schuh E, Patzig M, Zimmer C, Huber T
Clin Neuroradiol 2020 Jun;30(2):229-236. Epub 2019 Jan 9 doi: 10.1007/s00062-018-0755-4. PMID: 30627749

Diagnosis

Xie N, Sun Q, Yang J, Zhou Y, Xu H, Zhou L, Zhou Y
Orphanet J Rare Dis 2021 Jan 30;16(1):56. doi: 10.1186/s13023-021-01712-9. PMID: 33516249Free PMC Article
Mancuso M, Arnold M, Bersano A, Burlina A, Chabriat H, Debette S, Enzinger C, Federico A, Filla A, Finsterer J, Hunt D, Lesnik Oberstein S, Tournier-Lasserve E, Markus HS
Eur J Neurol 2020 Jun;27(6):909-927. Epub 2020 Mar 20 doi: 10.1111/ene.14183. PMID: 32196841
Hedderich DM, Lummel N, Deschauer M, Kümpfel T, Schuh E, Patzig M, Zimmer C, Huber T
Clin Neuroradiol 2020 Jun;30(2):229-236. Epub 2019 Jan 9 doi: 10.1007/s00062-018-0755-4. PMID: 30627749
Pelzer N, Hoogeveen ES, Haan J, Bunnik R, Poot CC, van Zwet EW, Inderson A, Fogteloo AJ, Reinders MEJ, Middelkoop HAM, Kruit MC, van den Maagdenberg AMJM, Ferrari MD, Terwindt GM
J Intern Med 2019 Mar;285(3):317-332. Epub 2018 Nov 8 doi: 10.1111/joim.12848. PMID: 30411414
Stam AH, Kothari PH, Shaikh A, Gschwendter A, Jen JC, Hodgkinson S, Hardy TA, Hayes M, Kempster PA, Kotschet KE, Bajema IM, van Duinen SG, Maat-Schieman MLC, de Jong PTVM, de Smet MD, de Wolff-Rouendaal D, Dijkman G, Pelzer N, Kolar GR, Schmidt RE, Lacey J, Joseph D, Fintak DR, Grand MG, Brunt EM, Liapis H, Hajj-Ali RA, Kruit MC, van Buchem MA, Dichgans M, Frants RR, van den Maagdenberg AMJM, Haan J, Baloh RW, Atkinson JP, Terwindt GM, Ferrari MD
Brain 2016 Nov 1;139(11):2909-2922. doi: 10.1093/brain/aww217. PMID: 27604306Free PMC Article

Therapy

de Boer I, Stam AH, Buntinx L, Zielman R, van der Steen I, van den Maagdenberg AMJM, de Koning EJP, Ferrari MD, de Hoon JN, Terwindt GM
Neurology 2018 Sep 4;91(10):e956-e963. Epub 2018 Aug 3 doi: 10.1212/WNL.0000000000006119. PMID: 30076273

Prognosis

Yan Y, Jiang S, Wang R, Wang X, Li P, Wu B
BMC Neurol 2021 Jun 9;21(1):219. doi: 10.1186/s12883-021-02250-4. PMID: 34107918Free PMC Article
Hedderich DM, Lummel N, Deschauer M, Kümpfel T, Schuh E, Patzig M, Zimmer C, Huber T
Clin Neuroradiol 2020 Jun;30(2):229-236. Epub 2019 Jan 9 doi: 10.1007/s00062-018-0755-4. PMID: 30627749

Clinical prediction guides

Hoogeveen ES, Pelzer N, Ghariq E, van Osch MJ, Dahan A, Terwindt GM, Kruit MC
J Cereb Blood Flow Metab 2021 Apr;41(4):831-840. Epub 2020 Jun 17 doi: 10.1177/0271678X20929430. PMID: 33736510Free PMC Article
Mancuso M, Arnold M, Bersano A, Burlina A, Chabriat H, Debette S, Enzinger C, Federico A, Filla A, Finsterer J, Hunt D, Lesnik Oberstein S, Tournier-Lasserve E, Markus HS
Eur J Neurol 2020 Jun;27(6):909-927. Epub 2020 Mar 20 doi: 10.1111/ene.14183. PMID: 32196841
Nagiel A, Lalane RA, Jen JC, Kreiger AE
Retin Cases Brief Rep 2018 Fall;12 Suppl 1:S87-S91. doi: 10.1097/ICB.0000000000000641. PMID: 29028736

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