Defining retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations.

Abstract

This scientific commentary refers to ‘Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations’, by Stam et al. (doi:10.1093/brain/aww217) . Cerebral small vessel diseases refer to pathological processes that affect the structure or function of small vessels of the brain, including arteries, arterioles, capillaries, and occasionally venules (Pantoni, 2010). While the majority of small vessel diseases are sporadic age-related conditions driven by a complex interaction between genetic and cardiovascular risk factors or cerebrovascular amyloid deposition, inherited (familial) cerebral small vessel diseases have been increasingly reported in recent years (Joutel and Faraci, 2014). Of these inherited diseases, CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) and Fabry’s disease are among the most prevalent (Pantoni, 2010). The list of other, rarely observed single-gene small vessel diseases, often with systemic manifestations outside the brain, seems to be steadily increasing, posing diagnostic challenges in clinical practice. One such disorder is the fatal autosomal dominant condition caused by mutations in TREX1 (three prime repair exonuclease 1). TREX1 encodes a 3′-5′ DNA exonuclease involved in clearing cytosolic nucleic acids (Richards et al. , 2007). The disease was originally reported under different names, including hereditary vascular retinopathy, cerebroretinal vasculopathy, and hereditary endotheliopathy with retinopathy, nephropathy, and stroke (HERNS), thought to represent distinct autosomal dominant neurovascular syndromes. The mapping of all three syndromes to a common locus on chromosome 3p21.1-p21.3 and the identification of pathogenic heterozygous C-terminal frame-shift mutations in TREX1 (Richards et al. , 2007 …