Retinal vasculopathy with cerebral leukodystrophy with systemic manifestations

Title

Other Names:

Cerebroretinal vasculopathy, hereditary; CRV; Retinopathy, vascular, with cerebral and renal involvement and Raynaud and migraine phenomena; Cerebroretinal vasculopathy, hereditary; CRV; Retinopathy, vascular, with cerebral and renal involvement and Raynaud and migraine phenomena; RVCL; Autosomal Dominant Retinal Vasculopathy with Cerebral Leukodystrophy; ADRVCL; Retinal vasculopathy and cerebral leukoencephalopathy; RVCL-S See More

Categories:

Congenital and Genetic Diseases; Eye diseases; Kidney and Urinary Diseases; Congenital and Genetic Diseases; Eye diseases; Kidney and Urinary Diseases; Musculoskeletal Diseases; Nervous System Diseases See More

Subtypes:

Hereditary vascular retinopathy

Summary Summary

Retinal vasculopathy with cerebral leukodystrophy and systemic manifestations (RVCL-S) affects the small blood vessels in the central nervous system and other organs. Symptoms begin in adulthood and can include loss of vision, Raynaud's disease, kidney and liver disease, and cognitive problems that get worse over time. Other symptoms may include migraines, gastrointestinal bleeding, and hypothyroidism. Death often occurs 10-15 years after the first symptoms appear. RVCL-S is caused by genetic variations in the TREX1 gene, and is inherited in an autosomal dominant pattern. Diagnosis is based on the symptoms, clinical exam, imaging studies of the brain, and may be confirmed by the results of genetic testing. Treatment is focused on managing the symptoms.^[1]^[2]^[3]

RVCL-S is considered to include the following three diseases which were previously thought to be separate conditions: hereditary endotheliopathy, retinopathy, nephropathy, and stroke (HERNS); cerebroretinal vasculopathy (CRV); and hereditary vascular retinopathy (HVR).^[1]

Last updated: 9/29/2020

Symptoms Symptoms

The following list includes the most common signs and symptoms in people with retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S). These features may be different from person to person. Some people may have more symptoms than others and symptoms can range from mild to severe. This list does not include every symptom or feature that has been described in this condition.

Symptoms of RVCL-S may include:^[1]^[2]^[3]

Vision problems due to retina damage (retinopathy)
Raynaud's disease
Kidney disease
Liver disease
Gastrointestinal bleeding
Hypertension
Cognitive problems
Psychiatric disorders

The first symptoms are Raynaud's disease and vision problems which may occur in the 20s. Vision problems tend to lead to blindness. Kidney and liver disease may occur in the 30s. Brain disease starts in the 40-50s. The symptoms of RVCL-S get worse over time, often leading to death in 10 to 15 years.^[2]^[3]

Last updated: 9/29/2020

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 69 |

Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Raynaud phenomenon		0030880
30%-79% of people have these symptoms
Abnormality of the hepatic vasculature	Abnormality of liver blood vessels	0006707
Brain imaging abnormality		0410263
Compensated hypothyroidism		0008223
Elevated alkaline phosphatase	Greatly elevated alkaline phosphatase High serum alkaline phosphatase Increased alkaline phosphatase Increased serum alkaline phosphatase [ more ]	0003155
Elevated gamma-glutamyltransferase level		0030948
Elevated serum creatinine	Elevated creatinine High blood creatinine level Increased creatinine Increased serum creatinine [ more ]	0003259
Glomerular sclerosis		0000096
Hypertension		0000822
Nephropathy		0000112
Nodular regenerative hyperplasia of liver		0011954
Normochromic anemia		0001895
Normocytic anemia		0001897
Proteinuria	High urine protein levels Protein in urine [ more ]	0000093
5%-29% of people have these symptoms
Anxiety	Excessive, persistent worry and fear	0000739
Apathy	Lack of feeling, emotion, interest	0000741
Aphasia	Difficulty finding words Losing words Loss of words [ more ]	0002381
Cardiomyopathy	Disease of the heart muscle	0001638
Cerebral calcification	Abnormal deposits of calcium in the brain	0002514
Depressivity	Depression	0000716
Focal hyperintensity of cerebral white matter on MRI		0040328
Focal hypointensity of cerebral white matter on MRI		0040331
Focal sensory seizure with somatosensory features		0011163
Gastrointestinal hemorrhage	Gastrointestinal bleeding	0002239
Generalized-onset seizure		0002197
Glaucoma		0000501
Hemianopia		0012377
Hemiparesis	Weakness of one side of body	0001269
Irritability	Irritable	0000737
Macular edema		0040049
Memory impairment	Forgetfulness Memory loss Memory problems Poor memory [ more ]	0002354
Micronodular cirrhosis		0001413
Migraine with aura		0002077
Migraine without aura		0002083
Pneumonia		0002090
Progressive neurologic deterioration	Worsening neurological symptoms	0002344
Psychosis		0000709
Retinal cotton wool spot		0031606
Retinal neovascularization		0030666
Sepsis	Infection in blood stream	0100806
Telangiectasia		0001009
Weakness of facial musculature	Decreased facial muscle strength Decreased strength of facial muscles Face weakness Facial muscle weakness Facial weakness Reduced facial muscle strength Weakness of face [ more ]	0030319
1%-4% of people have these symptoms
Avascular necrosis of the capital femoral epiphysis		0005743
Punctate vasculitis skin lesions		0200030
Skin rash		0000988
Percent of people who have these symptoms is not available through HPO
Abnormality of the periventricular white matter		0002518
Adult onset	Symptoms begin in adulthood	0003581
Apraxia		0002186
Autosomal dominant inheritance		0000006
Behavioral abnormality	Behavioral changes Behavioral disorders Behavioral disturbances Behavioral problems Behavioral/psychiatric abnormalities Behavioural/Psychiatric abnormality Psychiatric disorders Psychiatric disturbances [ more ]	0000708
Central nervous system degeneration		0007009
Dementia	Dementia, progressive Progressive dementia [ more ]	0000726
Diminished ability to concentrate	Poor concentration	0031987
Dysarthria	Difficulty articulating speech	0001260
Elevated erythrocyte sedimentation rate	High ESR	0003565
Elevated hepatic transaminase	High liver enzymes	0002910
Hematuria	Blood in urine	0000790
Limb pain		0009763
Lower limb hyperreflexia	Overactive lower leg reflex	0002395
Migraine	Intermittent migraine headaches Migraine headache Migraine headaches [ more ]	0002076
Progressive	Worsens with time	0003676
Progressive forgetfulness		0007017
Progressive visual loss	Progressive loss of vision Progressive vision loss Progressive visual impairment Slowly progressive visual loss Vision loss, progressive Visual loss, progressive [ more ]	0000529
Retinal exudate		0001147
Retinal hemorrhage	Retinal bleeding	0000573
Seizure		0001250
Stroke		0001297
Vasculitis in the skin		0200029
Visual impairment	Impaired vision Loss of eyesight Poor vision [ more ]	0000505

Showing of 69 |

Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 2/1/2021

Cause Cause

Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is caused by the TREX1 gene not working correctly. DNA changes known as pathogenic variants are responsible for making genes work incorrectly or sometimes, not at all.^[1]

Last updated: 9/29/2020

Inheritance Inheritance

Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is inherited in an autosomal dominant pattern.^[1] All individuals inherit two copies of each gene. Autosomal means the gene is found on one of the numbered chromosomes found in both sexes. Dominant means that only one altered copy of a gene is necessary to have the condition. The alteration can be inherited from either parent. Sometimes an autosomal dominant condition occurs because of a new genetic alteration (de novo) and there is no history of this condition in the family.

Each child of an individual with an autosomal dominant condition has a 50% or 1 in 2 chance of inheriting the alteration and the condition. Typically, children who inherit a dominant alteration will have the condition, but they may be more or less severely affected than their parent. Sometimes a person may have a gene alteration for an autosomal dominant condition and show no signs or symptoms of the condition.

Last updated: 9/29/2020

Diagnosis Diagnosis

Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is diagnosed based on the symptoms, clinical examination, and imaging studies of the brain. The diagnosis can be confirmed based on the results of genetic testing.^[1]^[3]

Last updated: 9/29/2020

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Treatment Treatment

Treatment of retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is focused on managing the symptoms.

Specialists involved in the care of someone with RVCL-S may include:^[1]

Ophthalmologist
Neurologist
Nephrologist
Liver specialist
Endocrinologist
Hematologist
Rheumatologist

Last updated: 9/29/2020

Statistics Statistics

There are about 200 reports of people with retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) in the medical literature.^[4] It is not known exactly how many people have this condition.

Last updated: 9/29/2020

Do you have updated information on this disease? We want to hear from you.

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from MedlinePlus Genetics.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Patient Registry

A registry supports research by collecting of information about patients that share something in common, such as being diagnosed with Retinal vasculopathy with cerebral leukodystrophy with systemic manifestations. The type of data collected can vary from registry to registry and is based on the goals and purpose of that registry. Some registries collect contact information while others collect more detailed medical information. Learn more about registries.

Registries for Retinal vasculopathy with cerebral leukodystrophy with systemic manifestations:
Myelin Disorders Bioregistry Project

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Energy 4 a Cure Foundation
5000 Eldorado Parkway, Suite 150, #403
Firsco, TX 75033
Telephone: 281-825-2854
E-mail: info@RVCLresearch.org
Website: http://www.rvclresearch.org/index.php

Organizations Providing General Support

Do you know of an organization? We want to hear from you.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

MedlinePlus Genetics contains information on Retinal vasculopathy with cerebral leukodystrophy with systemic manifestations. This website is maintained by the National Library of Medicine.

In-Depth Information

The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Retinal vasculopathy with cerebral leukodystrophy with systemic manifestations. Click on the link to view a sample search on this topic.

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

Have a question? Contact a GARD Information Specialist.

References References

de Boer I, Pelzer N, Terwindt G. Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations. GeneReviews. Updated Sept 19, 2020; https://www.ncbi.nlm.nih.gov/books/NBK546576.
Pelzer N, Hoogeveen ES, Haan J, Bunnik R, Poot CC, et al. Systemic features of retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations: a monogenic small vessel disease.. J Intern Med. Mar 2019; 285(3):317-332. https://pubmed.ncbi.nlm.nih.gov/30411414.
Stam AH, Kothari PH, Shaikh A, Gschwendter A, Jen JC, et al. Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations. Brain. Nov. 1, 2016; 139(11):2902-2922. https://pubmed.ncbi.nlm.nih.gov/27604306.
Ford AL, Chin VW, Fellah S, Binkley MM, Bodin AM, et al. Lesion evolution and neurodegeneration in RVCL-S: A monogenic microvasculopathy. Neurology. Sep 2020; 4:10. https://pubmed.ncbi.nlm.nih.gov/32887784.