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

TLDR

The study reports a Chinese American family with an autosomal dominant syndrome of retinopathy, nephropathy, and stroke affecting 11 members across three generations. Patients exhibited macular edema, retinal telangiectases, proteinuria, hematuria, migraine‑like headaches, psychiatric disturbances, dysarthria, hemiparesis, and apraxia, and neuroimaging showed contrast‑enhancing subcortical lesions with edema, and ultrastructural analysis revealed multilaminated vascular basement membranes, while genetic testing ruled out CADASIL, confirming a distinct autosomal dominant multi‑infarct syndrome.

Abstract

We describe a Chinese American family with a hereditary syndrome consisting of retinopathy, nephropathy, and stroke, affecting 11 members spanning three generations. Ophthalmologic evaluations revealed macular edema with capillary dropout and perifoveal microangiopathic telangiectases. Several members had renal abnormalities with proteinuria and hematuria. Initial manifestations were visual impairment and renal dysfunction; neurologic deficits occurred in the third or fourth decade of life. Symptoms included migraine-like headache, psychiatric disturbance, dysarthria, hemiparesis, and apraxia. Neuroimaging consistently demonstrated contrast-enhancing subcortical lesions with surrounding edema. Ultrastructural studies showed distinctive multilaminated vascular basement membranes in the brain and in other tissues, including the kidney, stomach, appendix, omentum, and skin. Genetic analysis ruled out linkage to the CADASIL locus on chromosome 19. Distinct from CADASIL, hereditary endotheliopathy with retinopathy, nephropathy, and stroke (HERNS) is an autosomal dominant multi-infarct syndrome with systemic involvement.