retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations

Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations

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 is associated witih DNA damage (chromosome damage) caused by a toxic mutant TREX1 protein, which causes organ damage mimicking radiation injury. RVCL affects small blood vessels, which disrupts blood flow to 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. Other organ are also involved in many cases, including the kidney, liver, gastrointestinal tract, thyroid, and bone. Symptoms of RVCL commonly begin between ages 35 and 55, 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 some patients live more than 20 years after initial symptoms. Clinical trials are underway, as are efforts to develop personalized medicines for patients with RVCL. The Clayco Foundation supports research efforts to develop treatments and a gene therapy for RVCL, working closely with physician-scientists at multiple academic institutions including at the University of Penns...