Retinal vasculopathy with cerebral leukocencephalopathy and systemic manifestations (RVCL or RVCL-S, also previously known as retinal vasculopathy with cerebral leukodystrophy, RVCL; or cerebroretinal vasculopathy, CRV; or hereditary vascular retinopathy, HVR; or hereditary endotheliopathy, retinopathy, nephropathy, and stroke, HERNS) is an inherited condition resulting from a frameshift mutation in the C-terminal region of the TREX1 gene. This disease affects  small blood vessels, leading to damage of multiple organs including but not limited to the retina and the white matter of the central nervous system. Patients with RVCL develop vision loss, brain lesions, strokes, brain atrophy, and dementia. Patients with RVCL also exhibit other organ involvement, including kidney, liver, gastrointestinal tract, thyroid, and bone disease. Symptoms of RVCL commonly begin between ages 40 and 50, although sometimes disease onset occurs earlier or later. The overall prognosis is poor, and death can sometimes occur within 5 or 10 years of the first symptoms appearing, although patients sometimes live about 20 years after initial symptoms. Clinical trials are underway, as are efforts to develop personalized medicines for patients with RVCL. Presentation
For most patients, disease onset is between ages 35 and 55. Earliest onset is usually not before age 35. Late onset is usually not after age 55. RVCL affects multiple organs. All patients develop brain and eye disease, leading to disability, vision loss, and premature death. All patients with RVCL develop kidney and liver disease, with elevated alkaline phosphatase. Some patients develop bone lesions (osteonecrosis) as well as hypothyroidism. Sometimes patients also develop gastrointestinal symptoms or bleeding.
1988: 10 families worldwide were identified as having CRV (now known as RVCL or RVCL-S)
1991: Related disease reported, HERNS (Hereditary Endiotheliopathy with Retinopathy, Nephropathy and Stroke – UCLA
1998: Related disease reported, HRV (Hereditary Retinal Vasculopathy) – Leiden University, Netherlands
2001: Localized to Chromosome 3. 2007: The specific genetic defect in all of these families was discovered in a single gene called TREX1 on chromosome 3. 2008: Name changed to AD-RVCL Autosomal Dominant-Retinal Vasculopathy with Cerebral Leukodystrophy
2009: Testing for the disease available to persons 21 and older
2011: 20 families worldwide were identified as having CRV
2012: Obtained mouse models for further research and to test therapeutic agents
2021: At least 42 families and 200 patients worldwide are known to have RVCL (or RVCL-S). [1]
2021: Dr. Jonathan Miner of the University of Pennsylvania (Penn) initiates the second clinical trial for RVCL, in collaboration with Dr. Andria Ford of WashU. Miner also establishes an International Registry in collaboration with colleagues. References


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