Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic Manifestations (RVCL-S)

Abstract

Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a systemic small vessel disease that affects various organs, including the brain, retina, kidneys, and liver. The disease is characterised by retinal vasculopathy, white matter lesions, focal and global brain dysfunction, and several systemic manifestations. These symptoms arise from C-terminal truncating mutations in the three prime repair exonuclease-1 (TREX1) gene. The mutations lead to the insertion of a premature stop codon, inducing the production of truncated proteins. How these truncated proteins exactly cause the disease manifestations is not yet known. However, prior studies appeared to indicate endothelial dysfunction as an important mechanism. Besides endothelial dysfunction, inflammation and serotonergic system malfunction have also been proposed as potential underlying mechanisms. Hence, these processes could potentially help to bridge the gap between the truncated TREX1 proteins and the clinical manifestations of RVCL-S. Therefore, the purpose of this review is to provide an overview of the main suggested theories concerning the pathophysiology of RVCL-S, including ideas for diagnostic markers and novel therapeutic targets