Over a five- to ten-year period, this vasculopathy (blood vessel pathology) results in vision loss and destructive brain lesions with neurologic deficits and death. Although brain and eye disease are universally present in patients with RVCL, the disease is truly a multi-system disorder characterized by chronic kidney disease, liver disease, and frequently other manifestations including gastrointestinal disease, osteonecrosis, and hypothyroidism. Diagnosis
Differential diagnosis
Treatment
Currently, there is no therapy that is proven to prevent the blood vessel deterioration. In 2021, Dr. Jonathan Miner of the University of Pennsylvania (Penn) in Philadelphia, and the Hospital of the University of Pennsylvania (Penn Medicine), initiated a clinical trial of crizanlizumab for RVCL. The University of Pennsylvania also sponsors RVCL patient support groups, and collaborates with the RVCL Research Center at Washington University (WashU) on clinical trials and longitudinal studies. Miner also established a large RVCL Research Center, which is conducting clinical trials, performing basic research, and developing novel personalized therapies for RVCL. This includes small molecular inhibitors (to be taken as pills) and gene therapy approaches, with the goal of fully correcting the disease-causing mutation. Developing these personalized therapies is a challenging process that will take years. History
1985–1988: CRV (Cerebral Retinal Vasculopathy) was discovered by multiple investigators including Dr. Gil Grand, Dr. John P. Atkinson, and colleagues at Washington University School of Medicine (WashU).
The normal function of the TREX1 gene is to provide instructions for making the 3-prime repair exonuclease 1 enzyme. This enzyme is a DNA exonuclease, which means it trims molecules of DNA by removing DNA building blocks (nucleotides) from the ends of the molecules. In this way, it breaks down unneeded DNA molecules or fragments that may be generated during genetic material in preparation for cell division, DNA repair, cell death, and other processes. Changes (mutations) to the TREX1 gene can result in a range of conditions, one of which is RVCL. The mutant TREX1 protein is produced and mislocalized. Haploinsufficiency of TREX1 does not explain the disease, since the parents of patients with Aicairdi-Goutieres syndrome, a disease characterized by insufficient TREX1 activity, are completely healthy with only one functional TREX1 allele. Different mutations in the TREX1 gene have also been identified in people with disorders involving the immune system. These disorders include a chronic inflammatory disease called Aicardi-Goutieres syndrome, as well as systemic lupus erythematosus (SLE), including a rare form of SLE called chilblain lupus that mainly affects the skin. Those diseases, which are inflammatory, may have a completely distinct mechanism compared with that of RVCL. The TREX1 gene is located on chromosome 3: base pairs 48,465,519 to 48,467,644

Pathogenesis
The main pathologic process centers on small blood vessels that prematurely "drop out" and disappear. The retina of the eye and white matter of the brain appear to be among the most sensitive to this pathologic process.