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

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.

Hereditary Systemic Angiopathy (HSA) with cerebral calcifications, retinopathy, progressive nephropathy, and hepatopathy

“…Compared to HSA, these syndromes are less systemic in nature, although hepatic involvement has been suspected in two CRV patients [22,28]. A combination of prominent retinopathy and systemic vasculopathy (HERNS) has been reported in a Chinese family [7]. In contrast to HSA, neither cerebral calcifications nor recurrent seizures have been reported in HERNS patients.…”

“…In contrast to HSA, neither cerebral calcifications nor recurrent seizures have been reported in HERNS patients. Furthermore, the clinical symptoms in HERNS patients neither include prominent liver and gastrointestinal dysfunction nor myopathy or cardiopathy [7,21]. An autosomal recessive cerebroretinal vasculopathy with cerebral calcifications has recently been reported in a German sister pair [15,16,20].…”

“…CADASIL is the prototypical example of a hereditary systemic small vessel disease and remains the only one which has been genetically characterized [9]. Other conditions with small vessel pathology include CARASIL [29], HERNS [7], CRV [5,28], HVR [17,23,25], HIHRTL [27] and a recently described syndrome with leukoencephalopathy, cerebral calcifications, and cysts [10,14]. HERNS, CRV and HRV have been linked to chromosome 3p21.1-3p21.3 [17] and may therefore have a common genetic origin.…”

Monogenic Vessel Diseases Related to Ischemic Stroke: A Clinical Approach

“…Magnetic resonance imaging reveals contrast-enhancing subcortical lesions with surrounding edema, especially in the frontoparietal region (Jen et al, 1997). However, the diagnosis is confirmed by genetic analysis.…”

“…Ultrastructural studies revealed alterations in arterioles and capillaries consisting in multilayered basement membrane in the brain and in other tissues such as kidney and skin biopsies (Jen et al, 1997).…”