title: 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.
authors.affiliation: Division of Genetics and Genomic Medicine, Department of Pediatrics, University of California, Irvine, CA, USA.
authors.forename: Abhilasha
authors.initials: A
authors.lastname: Surampalli
authors.affiliation: Departments of Anatomy & Neurobiology, University of Kentucky Medical College, Lexington, KY, USA.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Gold
authors.affiliation: Department of Neurology, University of Kentucky Medical College, Lexington, KY, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Smith
authors.affiliation: Division of Neuropathology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Rudy J
authors.initials: RJ
authors.lastname: Castellani
authors.affiliation: Division of Genetics and Genomic Medicine, Department of Pediatrics, University of California, Irvine, CA, USA.
authors.forename: Manaswitha
authors.initials: M
authors.lastname: Khare
authors.affiliation: Department of Radiology, University of California Irvine Medical Center, Orange, CA, USA.
authors.forename: Hon
authors.initials: H
authors.lastname: Yu
authors.affiliation: Child Development Center, Department of Pediatrics, University of California Irvine, Irvine, CA, USA.
authors.forename: Celeste
authors.initials: C
authors.lastname: Nguyen
authors.affiliation: Division of Genetics and Genomic Medicine, Department of Pediatrics, University of California, Irvine, CA, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Lan
authors.affiliation: Division of Genetics and Genomic Medicine, Department of Pediatrics, University of California, Irvine, CA, USA.
authors.forename: Marie
authors.initials: M
authors.lastname: Wencel
authors.affiliation: Child Development Center, Department of Pediatrics, University of California Irvine, Irvine, CA, USA.
authors.forename: Sharon
authors.initials: S
authors.lastname: Wigal
authors.affiliation: Departments of Orthopedics, Physiology & Biophysics, University of California Irvine, Irvine, CA, USA.
authors.forename: Vince
authors.initials: V
authors.lastname: Caiozzo
authors.affiliation: Division of Genetics and Genomic Medicine, Department of Pediatrics, University of California, Irvine, CA, USA. Electronic address: vkimonis@uci.edu.
authors.forename: Virginia
authors.initials: V
authors.lastname: Kimonis
mesh_terms: D015502:Absorptiometry, Photon; D000251:Adenosine Triphosphatases / Q000235:genetics*; D000469:Alkaline Phosphatase / Q000097:blood; D018797:Cell Cycle Proteins / Q000235:genetics*; D003402:Creatine Kinase / Q000097:blood; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D018979:Myositis, Inclusion Body / Q000097:blood / Q000235:genetics* / Q000473:pathology; D014427:Twins; D000074405:Valosin Containing Protein
chemical_list: D018797:Cell Cycle Proteins; D003402:Creatine Kinase; D000469:Alkaline Phosphatase; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein
keywords: Frontotemporal dementia screening; Inclusion body myopathy; Multisystem proteinopathy; Neuropsychological assessment; VCP