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ORPHA:247691

Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations

low confidenceDisorder

Also known as: RVCL · RVCL-S · Retinal vasculopathy and cerebral leukoencephalopathy

Publications

4,994

Trials

1

Interventional, condition-specific

Researchers

1,030

Distinct authors in sample

Gene link

TREX1

Definitive

Readiness

4/6

Stages with a signal

Clinical definition (Orphanet)

A rare genetic cerebral small vessel disease characterized by loss of visual acuity due to retinal vasculopathy, in combination with more variable neurological signs and symptoms including stroke, cognitive decline, migraine-like headaches, and , among others, typically beginning in middle age. Psychiatric features such as depression and anxiety may also occur. Systemic vascular involvement with Raynaud phenomenon, micronodular liver cirrhosis, and glomerular kidney dysfunction is present in a subset of patients.

How rare: How common this is has not been clearly measured.

Orphanet entry

Cross-references

Joined from Mondo / Orphanet. MeSH labels may enter searches; UMLS / OMIM / NCIT are stored for reference.

Additional Mondo synonyms (3)

hereditary vascular retinopathy · retinal vasculopathy and cerebral leukoencephalopathy · vasculopathy, retinal, with cerebral leukoencephalopathy and systemic manifestations

Research stages

Trial readiness signals

Where this condition sits on an open-data research pipeline — not how close a treatment is, and not medical advice. Empty stages often mean “not in these databases under this Mondo ID,” not “impossible.”

4/6 stages with a signal

An interventional trial matched this condition name on ClinicalTrials.gov — see trials below.

  1. Gene identifiedPresent

    Definitive — TREX1

  2. LiteraturePresent

    4,994 matched papers (3,571 in last 10 years) Source

  3. Phenotype characterisedPresent

    80 HPO annotations (e.g. Abnormal cerebral white matter morphology; Gastrointestinal hemorrhage; Cerebral calcification) Source

  4. Animal modelNot found

    No Alliance genotype “model of” associations via Monarch for these Mondo IDs

  5. Orphan designationNot found

    No FDA or EMA orphan-drug designation matched this disease via UMLS or preferred name Source

  6. Interventional trialPresent

    1 matched on ClinicalTrials.gov

Biology

Genes and phenotypes

Gene–disease validity from GenCC, plus phenotypes and animal models joined from Monarch Initiative via Mondo ID — not a clinical diagnosis aid.

Do we know what causes it?

Yes — we know a specific gene responsible (TREX1).

GenCC classification: Definitive.

Phenotypes (Monarch / HPO)

80

Associated phenotypes · MONDO:0008641

  • Abnormal cerebral white matter morphology
  • Gastrointestinal hemorrhage
  • Cerebral calcification
  • Focal sensory seizure with somatosensory features
  • Hemianopia

Showing 5 of 80 — open Monarch for the full list.

Animal models (Monarch / Alliance)

None returned for this Mondo ID. Empty here is not proof that no model organism work exists under another name or gene.

Monarch fetch 2026-07-29

Therapies

Designations, candidates, and chemicals

FDA OOPD and EMA orphan designations, Open Targets clinical candidates, and CTD chemical associations via MyDisease.info. These never change the interventional-trial headline.

Orphan designation (FDA · EMA)

No designation matched this disease via UMLS or preferred name on the FDA OOPD mirror or EMA orphan register. Absence here is not proof that none exists under another wording.

Open Targets candidates

1

Drugs / clinical candidates · MONDO_0008641

CTD chemicals (MyDisease.info)

No CTD chemical associations returned for this Mondo ID.

Literature

Is anyone studying this?

4,994

4,994 papers have been published on this condition. That is a real research literature — still far smaller than common diseases (breast cancer: over 700,000 papers). Median papers in the last 10 years for a rare disease in this dataset (publications denominator n=3967) is 59.

4,994 papers since the earliest indexed year in this search — median last-10-year count for a rare disease in this dataset is 59 (publications denominator n=3967).

3,571 in the last 10 years · low confidence

Phrase hits: 182 · MeSH hits: 0

Open Europe PMC search

Who's working on it?

1,030

Distinct author names in 182 sampled papers — named people below.

Who's working on it?

People publishing on this condition (sampled Europe PMC records). Affiliation is the most recent found in that sample.

  1. 01
    Terwindt GM17 papers · 2024

    Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.

    Papers in Europe PMC
  2. 02
    Miner JJ13 papers · 2026

    Department of Medicine and Microbiology, RVCL Research Center, and Colton Center for Autoimmunity, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.

    Papers in Europe PMC
  3. 03
    de Boer I10 papers · 2024

    Leiden University Medical Center, Leiden, the Netherlands.

    Papers in Europe PMC
  4. 04
    Pelzer N9 papers · 2024

    Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.

    Papers in Europe PMC
  5. 05
    Atkinson JP8 papers · 2026

    Department of Medicine, Division of Rheumatology, Washington University School of Medicine, St. Louis, MO.

    Papers in Europe PMC
  6. 06
    Ferrari MD7 papers · 2019

    Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands.

    Papers in Europe PMC
  7. 07
    van den Maagdenberg AMJM7 papers · 2020

    Leiden University Medical Center, Leiden, the Netherlands.

    Papers in Europe PMC
  8. 08
    Ford AL6 papers · 2026

    From the Department of Neurology (A.L.F., V.W.C., S.F., M.B.M., A.M.B., V.B., Y.T., P.K., Y.C., J.H., J.-M.L.), Mallinckrodt Institute of Radiology (A.L.F., J.-M.L., H.A.), Department of Ophthalmology (M.G.G.), and Department of Medicine (M.B., M.K.L., D.H., J.J.M., J.P.A.), Division of Rheumatology, Washington University School of Medicine, St. Louis, MO; Department of Radiology (D.L.), The Johns Hopkins University School of Medicine, Baltimore, MD; and Department of Neurology (J.C.J.), Icahn School of Medicine at Mount Sinai, New York, NY. forda@wustl.edu.

    Papers in Europe PMC
  9. 09
    Jen JC6 papers · 2021

    Departments of Neurology and Neurobiology, UCLA School of Medicine, Los Angeles, CA.

    Papers in Europe PMC
  10. 10
    Kruit MC6 papers · 2026

    Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.

    Papers in Europe PMC

Clinical research

Is a treatment being tested?

1

interventional trials for this specific condition

1 interventional trial matched this specific condition name; none in our sample are currently recruiting.

Data as of 11 September 2026 · last trial check 28 July 2026

1 interventional trial — more than 77.2% of diseases in the trials denominator have none at all (5501 of 7126; this disease is at the 80.1th percentile).

low confidence · 80.1th percentile (trials denominator)

Recruiting interventional trials

From the matched ClinicalTrials.gov set

1 interventional trials matched after quoted-phrase search and title/condition post-filter.

No currently recruiting studies in the matched set. Open the same search on ClinicalTrials.gov.

Other registries (secondary)

Broader net from EU CTIS, ISRCTN, and ICTRP when available — deduped against ClinicalTrials.gov IDs already counted above. Dual-model LLM relevance gates what we keep. These rows are not added to the interventional headline.

raw 0 · after dedupe 0 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 0 · dropped 0 · fetched 2026-07-30

Source notes: ictrp: Error: ICTRP public search unavailable (WHO portal is SPA-only; SOAP needs partnership). Tried: https://apps.who.int/tri

No secondary-registry studies passed dual-model relevance for this condition name (after dedupe).

Where to find support

Condition-specific patient organisations, when Orphanet lists them, are on the disease’s Orphanet page. We also link umbrella groups that support undiagnosed and ultra-rare families.

Orphanet entry for Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations — check Associations / patient organisations on that page.

India — NPRD

Last verified 2026-07-26

This ORPHAcode is not on our curated NPRD list (direct or Mondo-parent match). That does not decide clinical eligibility; families in India should ask a notified Centre of Excellence about current coverage.

Hand-curated for this project. ORPHAcode mappings are best-effort and may be incomplete or imprecise for umbrella categories. Parent (Mondo) matches mean the policy lists a broader category — confirm eligibility with a Centre of Excellence. Financial entitlements summarised from public policy statements and may change. This is not official government guidance.

How we counted this

Europe PMC query (preferred label + any corrected label + Orphanet and Mondo exact synonyms, stoplisted; unioned with resolved MeSH labels when available). UMLS / OMIM / NCIT cross-references are stored on the overview but are not added to the query string.

("Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations" OR "RVCL-S" OR "Retinal vasculopathy and cerebral leukoencephalopathy" OR "hereditary vascular retinopathy" OR "vasculopathy, retinal, with cerebral leukoencephalopathy and systemic manifestations") OR (MESH:"Vasculopathy, Retinal, With Cerebral Leukodystrophy") OR ("TREX1" OR "TREX1 syndrome" OR "TREX1-related")

Run this search on Europe PMC

MeSH descriptor terms unioned into the query: Vasculopathy, Retinal, With Cerebral Leukodystrophy

ClinicalTrials.gov query (quoted phrases + MeSH via query.cond, plus recall-expansion terms when used):

"Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations" OR "RVCL-S" OR "Retinal vasculopathy and cerebral leukoencephalopathy" OR "hereditary vascular retinopathy" OR "vasculopathy, retinal, with cerebral leukoencephalopathy and systemic manifestations" OR "Vasculopathy, Retinal, With Cerebral Leukodystrophy"

Interventional trials matched via: mesh (mesh = registered under a MeSH descriptor no name phrase would catch; recall-expansion = gene / selected parent terms used only for trials).

Study-type breakdown: 1 interventional · 0 observational · 0 expanded access. Only interventional studies enter the trial headline.

Query health: ok — strategies attempted: phrase, mesh; with hits: phrase, mesh

Run this search on ClinicalTrials.gov

Synonyms dropped by stoplist: RVCL

Confidence reasoning

  • Preferred label is multi-word and distinctive
  • 1 synonym(s) dropped by stoplist (may under-count)
  • "hereditary vascular retinopathy" also appears on ORPHA:71291
  • Publication count (4994) is extremely high with unknown/missing prevalence — treat as possible over-matching, not proven research intensity

Ingested 2026-07-27T10:34:55.088Z