Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic manifestations (RVCL-S): An update on basic...

Area of Science:

• Genetics
• Neurology
• Vascular Biology

Background:

• Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a rare, underrecognized systemic small vessel disease.
• It is caused by heterozygous C-terminal truncating TREX1 mutations, leading to vascular retinopathy, neurological deficits, cognitive decline, and systemic issues.
• The underlying pathology is a nonatherosclerotic, amyloid-negative angiopathy affecting small arteries and capillaries.

Purpose of the Study:

• To highlight the importance of timely recognition of RVCL-S to manage complications and avoid unnecessary procedures.
• To emphasize the need for translational research combining basic science and clinical findings to understand RVCL-S pathophysiology.
• To identify potential biomarkers and therapeutic strategies for RVCL-S patients.

Main Methods:

• Review of existing literature on RVCL-S and TREX1 mutations.
• Analysis of clinical manifestations and pathological findings in RVCL-S patients.
• Discussion of future research directions, including translational studies and natural history investigations.

Main Results:

• RVCL-S is characterized by a distinct clinical and pathological profile, including retinopathy, neurological and systemic manifestations, and premature death.
• The exact mechanisms linking truncated TREX1 protein to angiopathy are currently unknown.
• Early diagnosis is crucial for effective management and prevention of complications.

Conclusions:

• Further translational research is critical to elucidate the pathophysiology of RVCL-S.
• Identifying biomarkers and therapeutic targets will improve patient care and outcomes.
• A comprehensive understanding of RVCL-S natural history is needed for effective disease management.