A 44-year-old man with eye, kidney, and brain dysfunction

Abstract

Retinal vasculopathy with cerebral leukodystrophy (RVCL) is a rare, autosomal dominant condition caused by mutations of TREX1 (3-prime repair exonuclease-1). The phenotypic expressions range from isolated retinal involvement to varying degrees of retinopathy, cerebral infarction with calcium depositions, nephropathy, and hepatopathy. We report a case of RVCL caused by a novel TREX1 mutation. This patient's multisystem presentation, retinal involvement interpreted as "retinal vasculitis," and improvement of neuroimaging abnormalities with dexamethasone led to the accepted diagnosis of a rheumatologic disorder resembling Behçet disease. Clinicians should consider RVCL in any patient with retinal capillary obliterations associated with tumefactive brain lesions or nephropathy.

Figure 1

Neuroimaging on hospital admission. Axial fluid-attenuated inversion recovery (FLAIR; A) magnetic resonance imaging (MRI) of the brain showed a left cerebellar lesion and a right temporo-parieto-occipital tumefactive lesion with confluent white matter hyperintensities that extended through the splenium of the corpus callosum into the left periventricular white matter. Axial diffusion-weighted imaging (DWI; B left) paired with apparent diffusion coefficient (ADC; B right) map revealed foci of restricted diffusion. Gadolinium was not administered due to renal insufficiency. Computerized tomography (CT) of the head demonstrated punctate calcifications scattered throughout the frontal white matter (arrowheads).

Figure 2

Fluorescein angiography of the left eye on admission to our hospital. Extensive retinal ischemia with enlargement of the foveal avascular zone (arrowhead), perivascular fluorescein leakage (curved arrow), hyperfluorescence of vessel walls (arrows), and numerous scars in the retinal periphery from pan-retinal photocoagulation are illustrated.

Figure 3

Brain histopathology, hematoxylin and eosin. The white matter has ill-defined areas of necrosis with dystrophic calcification, with margins that appear to have ischemic changes (A; scale bar: 150 µm). The small blood vessels in the tissue surrounding the areas of necrosis have abnormally thickened walls (B, C; scale bar: 75 µm). Other angiomatoid vascular proliferations are associated with mild chronic inflammatory infiltrate (D; scale bar: 40 µm).

Figure 4

Axial FLAIR MRI of the brain following a 10-week course of high-dose dexamethasone. Note the prominent decrease in the white matter edema with resolution of the mass effect, and postsurgical changes in the right parietal lobe (arrowhead).