Hereditary endotheliopathy with retinopathy, nephropathy, and stroke (HERNS)

Grand et al. (1988) reported an American family with a cerebroretinal vasculopathy (CRV) with recurrent strokes and visual loss due to characteristic retinal capillary abnormalities. Shortly afterward, Gutmann et al. (1989) described another American family with a similar syndrome of progressive visual loss and leukoencephalopathy without other organ involvement. In 1997, we reported a large Chinese family that presented with a hereditary vasculopathy similar to CRV with subcortical leukoencephalopathy and retinopathy but that also had renal dysfunction (Jen et al., 1997). Ultrastructural studies identified characteristic alterations of vascular basement membranes not previously described; therefore, the syndrome was named hereditary endotheliopathy with retinopathy, nephropathy, and stroke (HERNS). Finally, Terwindt et al. (1998) described a Dutch family with hereditary vascular retinopathy (HVR) with microangiopathy of the retina similar to the above noted families, but without central nervous system involvement. Recently, a genome-wide linkage analysis of the Dutch family with HVR mapped the disease locus to chromosome 3p, which was also consistent with linkage in CRV and HERNS, suggesting that they are allelic syndromes (Ophoff et al., 2001) (Table 36.1). Mutations in TREX1, a gene that codes for a 3'-5' DNA exonuclease, were found in all of these families (Richards et al., 2007).