Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations

See Charidimou (doi: 10.1093/aww253 ) for a scientific commentary on this article . Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic Manifestations is a newly recognised and often misdiagnosed neurovascular syndrome caused by mutations in TREX1 . Stam et al . provide the first comprehensive clinical, pathological and radiological characterization of RVCL-S, and highlight cerebral mass lesions, impaired liver and kidney function, and premature death. See Charidimou (doi: 10.1093/aww253 ) for a scientific commentary on this article . Retinal Vasculopathy with Cerebral Leukoencephalopathy and Systemic Manifestations is a newly recognised and often misdiagnosed neurovascular syndrome caused by mutations in TREX1 . Stam et al . provide the first comprehensive clinical, pathological and radiological characterization of RVCL-S, and highlight cerebral mass lesions, impaired liver and kidney function, and premature death. See Charidimou (doi: 10.1093/aww253 ) for a scientific commentary on this article . Cerebroretinal vasculopathy, hereditary vascular retinopathy, and hereditary endotheliopathy, retinopathy, nephropathy and stroke are neurovascular syndromes initially described as distinct entities. Recently they were shown to be one disease caused by C-terminal frame-shift mutations in TREX1 , which was termed ‘retinal vasculopathy with cerebral leukodystrophy’. Here we defined the genetic and clinicopathologic spectrum of this clinically and pathophysiologically poorly characterized and frequently misdiagnosed fatal neurovascular disorder. We identified five different TREX1 mutations in 78 members from 11 unrelated families and by using a standardized study protocol we retrospectively reviewed and aggregated the associated clinical, neuroimaging, and pathology data. Findings were similar across mutations and families. Sixty-four mutation carriers had vascular retinopathy. Neuroimaging revealed (i) punctate, hyperintense, white matter lesions with or without nodular enhancement in 97% of them; (ii) rim-enhancing mass lesions in 84%; and (iii) calcifications in the white matter in 52%. Ninety per cent had clinical manifestations of brain disease, including focal neurological deficits (68%), migraine (59%), cognitive impairment (56%), psychiatric disturbances (42%), and seizures (17%). One mutation carrier had enhancing brain lesions and neurological features but unknown retinopathy status. Additional systemic features included liver disease (78%