Autosomal Dominant Subcortical Gliosis Presenting as Frontotemporal Dementia: Clinical and Histopathological Descriptions

Abstract

We describe a multigenerational kindred with a frontotemporal dementia clinical syndrome (FTDS), extensive subcortical gliosis neuropathology and autosomal dominant genetics. Members of the unique kindred now reported were evaluated at the University of Virginia. Studies were performed in order to establish the likely presence of an underlying neurodegenerative pathogenesis. An extended family tree was assembled. Results from five prospective brain autopsy evaluations and one retrospective brain autopsy were considered. Kindred members affected with this FTDS syndrome have extensive subcortical gliosis capping the frontal horns of the lateral ventricles, evident by neuroradiologic examination. Histopathologic analyses show florid subcortical gliosis, and reveal neither tau nor ubiquitin inclusions. The presence of both maternal and paternal transmission indicate this is an autosomal dominant disorder. Subcortical gliosis in this kindred is either due to mutation of a novel gene, or else represents a unique, previously unrecognized FTDS variant caused by mutation of an already known gene. The kindred is extensive enough to facilitate linkage analysis. Determining the basis of this kindred's autosomal dominant subcortical gliosis could potentially yield mechanistic insight into vascular‐attributed cognitive impairment/dementia syndromes.