Inclusion body myopathy (IBM) associated with Paget disease of the bone (PDB) and frontotemporal dementia (FTD) or Inclusion Body associated with Paget disease of the bone and frontotemporal dementia (IBMPFD), or Multisystem Proteinopathy (MSP1) is an autosomal dominant degenerative disorder caused by mutations in the valosin-containing protein (VCP) gene. We aim to establish a detailed clinical phenotype of VCP disease amongst 112 (90 affected individuals, 12 presymptomatic gene carriers) individuals versus 37 unaffected first-degree relatives to establish useful biomarkers for VCP myopathy and identify the most meaningful tests for monitoring disease progression. Comprehensive studies included the Inclusion Body Myositis Functional Rating Scale (IBMFRS) and fatigue severity scale (FSS) questionnaires, strength measurements using the Manual Muscle Test with Medical Research Council (MRC) scales, hand-held dynamometry using the microFET and Biodex dynamometers, 6 minute walk test, pulmonary function studies, and genotype-phenotype correlations.
The mean MRC whole body total score for the affected individuals was 105.17 compared to the score in carriers (125.83), and unaffected individuals (130) Significant differences were found of the proximal muscle groups affecting shoulder abduction and hip flexion. however, the distal muscle groups strength is retained. As a result of our studies, we found correlations between IBMFRS and MRC (r=0.793, p<0.01), 6MWT (r=0.734, p<0.01) and a significant, yet low, negative correlation (r=-0.477, p=0.008) with the FSS. These results indicate that IBMFRS can be used for assessing motor function in patients with VCP disease and can be used to monitor the progression of motor involvement in VCP disease. Pulmonary function tests revealed compromised lung function due to myopathic involvement of the diaphragm and other accessory muscles of respiration. Based on the MRC scale results, FSS and 6MWT test scores the presymptomatic carriers showed muscle weakness in their shoulders and hips. This study represents a comprehensive evaluation of individuals with VCP MSP1 and provides a useful guide for evaluating and possible monitoring of muscle weakness and pulmonary function progression in this unique cohort of individuals.