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

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Abstract

Several hereditary conditions affecting cerebral, retinal and systemic microvessels have recently been described. They include CADASIL, CRV, and HERNS. We here report on a variant form of a hereditary systemic angiopathy (HSA) affecting two generations of a Caucasian family. Clinical symptoms of HSA appear in the mid-forties and are characterized by visual impairment, migrainelike headache, skin rash, epileptic seizures, progressive motor paresis and cognitive decline. Late symptoms include hepatic and renal failure. Retinal capillary microaneurysms and arteriolar tortuosity are associated with marked optic disc atrophy. Radiological hallmarks consist of multiple cerebral calcifications and tumor-like subcortical white matter lesions. Brain, peripheral nerve, muscle, kidney and colon biopsies have revealed a multi organ small vessel involvement with partly altered endothelium, perivascular inflammation and thrombotic microangiopathy.

No curative therapeutic options are known for hereditary cerebral vasculopathies. The use of cyclophosphamide, azathioprine and methotrexate was of no benefit in our cases of HSA. Early diagnosis of hereditary systemic angiopathies is important in order to prevent patients from repetitive invasive diagnostic measures and to avoid the use of inappropriate and potentially harmful drugs.

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Abbreviations

HSA:

hereditary systemic angiopathy

ADAMTS:

a disintegrin-like and metalloproteinase with thrombospondin motifs

CADASIL:

cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

CARASIL:

cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy

CRV:

cerebroretinal vasculopathy

HERNS:

hereditary endotheliopathy with retinopathy, nephropathy, and stroke

HIHRTL:

hereditary infantile hemiparesis, retinal arteriolar tortuosity, and leukoencephalopathy

MELAS:

mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes

vWF:

von Willebrand factor

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Authors and Affiliations

  1. Dept. of Neurology, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland

    D. T. Winkler MD, PhD, P. Lyrer MD & A. J. Steck MD

  2. Dept. of Neuropathology, Institute of Pathology, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland

    D. T. Winkler MD, PhD, A. Probst MD, M. J. Mihatsch MD & M. Tolnay MD

  3. Institut de Génétique et de Biologie, Moléculaire et Cellulaire, CNRS/INSERM/ULP, 10142, 67404, Illkirch Cedex CU de Strasbourg, France

    D. Devys MD, PhD

  4. University Eye Clinic, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland

    T. Haufschild MD

  5. Dept. of Neuroradiology, Institute of Radiology, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland

    S. Haller MD

  6. Cantonal Institute of Pathology, Mühlemattstrasse 22, 4410, Liestal, Switzerland

    N. Willi MD

  7. Institute of Pathology, University Hospital Basel, Schönbeinstrasse 40, 4031, Basel, Switzerland

    M. Tolnay MD

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  1. D. T. Winkler MD, PhD
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Correspondence to M. Tolnay MD.

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Winkler, D.T., Lyrer, P., Probst, A. et al. Hereditary Systemic Angiopathy (HSA) with cerebral calcifications, retinopathy, progressive nephropathy, and hepatopathy. J Neurol 255, 77–88 (2008). https://doi.org/10.1007/s00415-008-0675-3

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  • DOI: https://doi.org/10.1007/s00415-008-0675-3

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