A case report comparing clinical, imaging and neuropsychological assessment findings in twins discordant for the VCP p.R155C mutation

Abstract

Inclusion body myopathy, Paget disease of bone and/or frontotemporal dementia is an autosomal dominant disease caused by mutations in the Valosin Containing Protein (VCP) gene. We compared clinical findings including MRI images and neuropsychological assessment data in affected and unaffected twin brothers aged 56 years from a family with the p.R155C VCP gene mutation. The affected twin presented with a 10 year history of progressive proximal muscle weakness, difficulty swallowing, gastroesophageal reflux, fecal incontinence, and peripheral neuropathy. Comprehensive neuropsychological testing revealed rapid cognitive decline in the absence of any behavioral changes in a span of 1 year. This case illustrates that frontotemporal dementia related cognitive impairment may precede behavioral changes in VCP disease as compared with predominance of behavioral impairment reported in previous studies. Our findings suggest that there is a need to establish VCP disease specific tools and normative rates of decline to detect pre-clinical cognitive impairment among affected individuals.

Keywords: Frontotemporal dementia screening; Inclusion body myopathy; Multisystem proteinopathy; Neuropsychological assessment; VCP.

Conflict of interest statement

No conflicts of interest.

Copyright © 2014 Elsevier B.V. All rights reserved.

Figures

Figure 1

T1-weighted sagittal MRI images of the affected (A) and unaffected (B) twins at age 55y. and brain volumes from MRI scans performed at age 55 y.

Figure 2

MRI of thighs and Biodex measurements from twins discordant for the VCP disease. Pixel-intensity histograms of the segmented muscle group in T2-weighted histograms of (A) Control twin and (B) Affected twin (C) Biodex measurements of control and affected twins of VCP disease.

Figure 3

Frontal cortex stained with hematoxylin and eosin shows nonspecific perineuronal vacuolation. Ubiquitin immunohistochemistry was nonspecific in the cerebral cortex and white matter. Scale bar = 200 μm.