Valosin-containing protein (VCP)-associated multisystem
proteinopathy (MSP) is a rare
genetic disorder with abnormalities in the autophagy pathway leading to various combinations of
myopathy,
bone diseases, and neurodegeneration. Ninety percent of patients with VCP-associated MSP have
myopathy, but there is no consensus-based guideline. The goal of this working group was to develop a best practice set of provisional recommendations for VCP
myopathy which can be easily implemented across the globe. As an initiative by Cure VCP Disease Inc., a patient advocacy organization, an online survey was initially conducted to identify the practice gaps in VCP
myopathy. All prior published literature on VCP
myopathy was reviewed to better understand the different aspects of management of VCP
myopathy, and several working group sessions were conducted involving international experts to develop this provisional recommendation. VCP
myopathy has a heterogeneous clinical phenotype and should be considered in patients with
limb-girdle muscular dystrophy phenotype, or any
myopathy with an autosomal dominant pattern of inheritance. Genetic testing is the only definitive way to diagnose VCP
myopathy, and single-variant testing in the case of a known familial VCP variant, or multi-gene panel sequencing in undifferentiated cases can be considered. Muscle biopsy is important in cases of diagnostic uncertainty or lack of a definitive pathogenic genetic variant since rimmed vacuoles (present in ~40% cases) are considered a hallmark of VCP
myopathy. Electrodiagnostic studies and magnetic resonance imaging can also help rule out disease mimics. Standardized management of VCP
myopathy will optimize patient care and help future research initiatives.