# Exploring targeted therapy in retinal vasculopathy with cerebral leukoencephalopathy: a case report and review of literature

## TL;DR

A patient with a rare genetic disorder shows new symptoms and a family study reveals similar immune changes, suggesting the need for early monitoring.

## Contribution

This case expands the known phenotypic spectrum of RVCL-S and highlights the value of immunological monitoring in carriers.

## Key findings

- A TREX1 mutation carrier showed sarcoidosis-like pulmonary granulomas alongside classic RVCL-S symptoms.
- Transcriptomic analysis in the patient and asymptomatic daughter revealed mild upregulation of inflammatory pathways.
- Treatment with a Janus kinase inhibitor led to transient clinical stabilization in the patient.

## Abstract

Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a rare autosomal dominant microvascular disorder caused by C-terminal truncating mutations in TREX1 gene, which impair protein localization and lead to multisystem involvement. We report a patient carrying the pathogenic TREX1 variant NM_033629.6:c.703dup (p.Val235fs), the most frequently described mutation in RVCL-S, whose clinical course was consistent with the classic phenotype but with simultaneous pulmonary granulomatous lesions compatible with sarcoidosis. Transcriptomic analysis in both the patient and his pre-asymptomatic daughter, who carries the same variant, revealed a similarly mild upregulation of inflammatory signaling pathways. Treatment with a Janus kinase inhibitor in the patient was followed by transient clinical stabilization before subsequent progression. This case expands the phenotypic spectrum of RVCL-S and underscores the importance of systematic immunological monitoring and clinical surveillance to support future development of timely strategies in asymptomatic carriers.