Corticobasal Degeneration and Frontotemporal Dementia Presentations in a Kindred with Nonspecific Histopathology

Abstract

We report the clinical, neuropsychological, electroencephalographic and radiologic findings in a kindred with varying clinical presentations of a neurodegenerative disorder. Postmortem examination of one member with clinically suspected corticobasal degeneration (CBD) revealed nonspecific histopathology maximally involving the frontoparietal cortex with negligible degenerative changes in the basal ganglia and substantia nigra. The findings in this and other kindreds demonstrate that (1) similar findings on ancillary testing can occur in relatives presumably suffering from the same pathophysiologic process despite dissimilar clinical presentations, (2) the ‘CBD syndrome’ is not specific for CBD, (3) extrapyramidal dysfunction can exist in the absence of appreciable basal ganglia and nigral degeneration, (4) nonspecific histopathology can underlie familial focal/asymmetric cortical degeneration syndromes and (5) many of the findings in CBD are comparable to those reported in frontotemporal dementia.

Prominent phenotypic variability associated with mutations in Progranulin

“…Four of our cases with PGRN mutations had striking increased signal in the subcortical white matter adjacent to the cortical regions where atrophy was maximal, and in two other cases with focal temporal lobe atrophy, milder degrees of subcortical signal changes were present. Few FTDP cases with PGRN mutations and MRI scans have been reported, and the MR images and data presented in this report, along with our other reports (Boeve et al 2002;, provide far more detail than other reports of PGRN mutation families. The relative sensitivity and specificity of these subcortical signal changes for cases harboring a PGRN mutation remains to be determined.…”

“…This hemispheric predilection has not been described in kindreds with mutations in MAPT. As previously suggested (Boeve et al 2002), some genetic factors may dictate the development of neurologic disease, while others may determine the neurodegenerative topography, analogous to prion disease (Goldfarb et al 1992).…”

“…Representative MRI scans are shown in Figure 2, and Figure 3 is a schematic drawing localizing the mutations in PGRN. Descriptions of Kindred 7 (Mesulam et al 2007), two members of Kindred 1 (Boeve et al 2002) and the proband of Kindred 5 ) have previously been reported.…”

Similar clinical and neuroimaging features in monozygotic twin pair with mutation in progranulin

“…Neurology Familial frontotemporal dementia (FTD) due to mutations in progranulin (PGRN) has been associated with a broad spectrum of phenotypic variability, including behavioral variant FTD, primary progressive aphasia, corticobasal syndrome, an anterograde amnesic disorder similar to Alzheimer disease dementia, and a syndrome resembling Lewy body dementia. [1][2][3][4][5][6][7] There has been a wide range in age at onset, implying probable nongenetic as well as individual differences in disease expression along with additional modifying factors such as single nucleotide polymorphisms.…”

“…[1][2][3][4][5][6][7] There has been a wide range in age at onset, implying probable nongenetic as well as individual differences in disease expression along with additional modifying factors such as single nucleotide polymorphisms. 8 Monozygotic twins provide a unique opportunity to better understand the manifestations of autosomal dominant inherited neurodegenerative diseases.…”