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Disease Profile

Retinal vasculopathy with cerebral leukodystrophy with systemic manifestations

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

-

ICD-10

-

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Cerebroretinal vasculopathy, hereditary; CRV; Retinopathy, vascular, with cerebral and renal involvement and Raynaud and migraine phenomena;

Categories

Congenital and Genetic Diseases; Eye diseases; Kidney and Urinary Diseases;

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]

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]

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.

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

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]

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 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

    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

      Organizations Providing General Support

          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.

              References

              1. 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.
              2. 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.
              3. 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.
              4. 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.

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