Open AccessNeuropathology and Genetics of Cerebroretinal Vasculopathies
Author(s) -
Kolar Grant R.,
Kothari Parul H.,
Khanlou Negar,
Jen Joanna C.,
Schmidt Robert E.,
Vinters Harry V.
Publication year - 2014
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/bpa.12178
Subject(s) - pathology , fibrinoid necrosis , cadasil , leukodystrophy , neuropathology , leukoencephalopathy , medicine , frameshift mutation , biology , mutation , genetics , disease , vasculitis , gene
Cerebroretinal vasculopathy ( CRV ) and the related diseases hereditary endotheliopathy with retinopathy, neuropathy, and stroke ( HERNS ), hereditary vascular retinopathy ( HVR ) and hereditary systemic angiopathy ( HSA ) [subsequently combined as retinovasculopathy and cerebral leukodystrophy ( RVCL )] are devastating autosomal‐dominant disorders of early to middle‐age onset presenting with a core constellation of neurologic and ophthalmologic findings. This family of diseases is linked by specific mutations targeting a core region of a gene. Frameshift mutations in the carboxyl‐terminus of t hree p rime e xonuclease‐ 1 ( TREX 1), the major mammalian 3′ to 5′ DNA exonuclease on chromosome 3p21.1‐p21.3, result in a systemic vasculopathy that follows an approximately 5‐year course leading to death secondary to progressive neurologic decline, with sometimes a more protracted course in HERNS . Neuropathological features include a fibrinoid vascular necrosis or thickened hyalinized vessels associated with white matter ischemia, necrosis and often striking dystrophic calcifications. Ultrastructural studies of the vessel walls often demonstrate unusual multilaminated basement membranes.