A Novel TREX1 Frameshift Variant (c.802del p. (Arg268Glyfs*9) Associated with Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic Manifestations: a Case Report

Background: Report a Novel TREX1 Frameshift Variant (c.802del p. (Arg268Glyfs*9) associated with Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic Manifestations (RVCL-S) and accompanying clinical features of the disease. Case presentation: A 42-year-old male with multiple substance abuse disorder presented to the emergency room in a state of confusion with worsening headaches. Neuroimaging (Computed Tomography scan/ Magnetic Resonance Imaging scan) was performed and brain mass with midline shift was noted. The differential diagnoses included brain abscess versus multiple sclerosis or mass lesion. Extensive workup did not confirm infection or demyelinating disease. Treatment with broad spectrum antibiotics yielded no benefit and brain biopsy showed inflammatory necrosis only. In addition to his brain lesions, peripheral neovascular retinopathy was found and treated with laser photocoagulation. He had a positive family history of retinal vasculopathy with cerebral leukodystrophy (RVCL) affecting father, paternal grandmother, and paternal cousins. Genetic testing showed a pathogenic TREX1 c.802del p. (Arg268Glyfs*9) variant. To our knowledge, this variant and its accompanying clinical features have not been previously reported. Conclusions: Retinal vasculopathy with cerebral leukodystrophy and systemic manifestations (RVCL-S) is a rare, autosomal dominant microangiopathy caused by truncating TREX 1 mutations, characterized by vascular retinopathy, neurological features, cognitive decline, Raynaud’s phenomenon, anemia, and renal and hepatic involvement. The patient developed avascular necrosis of the femur. We describe clinical, ophthalmic, radiographic, and systemic features of this 42-year-old male with the novel TREX1 c.802del p. (Arg268Glyfs*9) variant with a review of the literature. Cerebral lesions with surrounding edema often require corticosteroid therapy and early recognition of RVCL-S may prevent unnecessary invasive procedures. There is no cure and patients are at risk for premature death. A genetic evaluation is essential to establish the diagnosis.