Author(s): Authors Kimonis V, Donkervoort S, Watts G
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Excerpt CLINICAL CHARACTERISTICS: Inclusion body myopathy associated with Paget disease of bone (PDB) and/or frontotemporal dementia (IBMPFD) is characterized by adult-onset proximal and distal muscle weakness (clinically resembling a limb-girdle muscular dystrophy syndrome), early-onset PDB, and premature frontotemporal dementia (FTD). Muscle weakness progresses to involve other limb and respiratory muscles. Cardiac failure and cardiomyopathy have been observed in later stages. PDB involves focal areas of increased bone turnover that typically lead to spine and/or hip pain and localized enlargement and deformity of the long bones; pathologic fractures occur on occasion. Early stages of FTD are characterized by dysnomia, dyscalculia, comprehension deficits, paraphasic errors, and relative preservation of memory, and later stages by inability to speak, auditory comprehension deficits for even one-step commands, alexia, and agraphia. Mean age at diagnosis for muscle disease and PDB is 42 years; for FTD, 55 years. DIAGNOSIS/TESTING: In IBMPFD, the diagnosis of muscle disease is based on serum CK concentration, electromyogram (EMG), and skeletal muscle histology; the diagnosis of PDB is based on serum alkaline phosphatase (ALP) concentration, urine concentrations of pyridinoline (PYD) and deoxypyridinoline (DPD), and skeletal radiographs or radionuclide scan; and the diagnosis of FTD is based on on comprehensive neuropsychological assessment. VCP is the only gene in which mutation is known to cause IBMPFD. MANAGEMENT: Treatment of manifestations: Weight control to avoid obesity; physical therapy and stretching exercises to promote mobility and prevent contractures; mechanical aids (canes, walkers, orthotics, wheelchairs) for ambulation/mobility; surgical intervention for foot deformity and scoliosis; respiratory aids when indicated; social and emotional support; assisted living arrangements for muscle weakness and/or dementia; bisphosphonates to relieve pain and disability from PDB. Surveillance: At periodic intervals: echocardiogram and EKG to monitor for evidence of cardiomyopathy; pulmonary function studies; alkaline phosphatase, skeletal x-rays and bone scans to monitor for PDB onset and effectiveness of therapy; assessment of behavior and mental status. GENETIC COUNSELING: IBMPFD is inherited in an autosomal dominant manner. An estimated 80\% of affected individuals have an affected parent; approximately 20\% have the disorder as a result of de novo mutation. Each child of an individual with IBMPFD has a 50\% chance of inheriting the pathogenic variant. Prenatal testing for pregnancies at increased risk is possible if the pathogenic variant in the family is known. Copyright © 1993-2016, University of Washington, Seattle. All rights reserved.
This article was published in Inclusion Body Myopathy with Paget Disease of Bone and/or Frontotemporal Dementia
and referenced in Journal of Stem Cell Research & Therapy