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

Neuromuscul Disord. 2015 Feb;25(2):177-83. doi: 10.1016/j.nmd.2014.10.003. Epub 2014 Oct 22.

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.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorptiometry, Photon
  • Adenosine Triphosphatases / genetics*
  • Alkaline Phosphatase / blood
  • Cell Cycle Proteins / genetics*
  • Creatine Kinase / blood
  • DNA Mutational Analysis
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Middle Aged
  • Mutation / genetics*
  • Myositis, Inclusion Body / blood
  • Myositis, Inclusion Body / genetics*
  • Myositis, Inclusion Body / pathology
  • Twins
  • Valosin Containing Protein

Substances

  • Cell Cycle Proteins
  • Creatine Kinase
  • Alkaline Phosphatase
  • Adenosine Triphosphatases
  • VCP protein, human
  • Valosin Containing Protein