Science News: VCP-Related Myopathy: A Case Series and a Review of Literature

Published October 26, 2023

Science News

Submitted by: Justin Willer, MD
Edited by: Pritikanta Paul, MD

Citation: Iannibelli E, Gibertini S, Cheli M, et al. VCP-related myopathy: a case series and a review of literature. Acta Myol. 2023;42(1):2-13. Published 2023 Mar 31. doi:10.36185/2532-1900-2444

Summary: Valosin containing protein (VCP) controls the ubiquitin proteasome system, endolysosomal sorting, and autophagy. Frontotemporal dementia, inclusion body myopathy, and Paget’s disease of bone all have been related to dominant missense mutations in the VCP gene causing a multisystem proteinopathy.

In this study, the authors describe a series of five patients with VCP mutations, a majority with lower limb weakness with distal predominance. Beevor’s sign suggesting lower abdominal muscle weakness was noted in two patients never described before in VCP related myopathy. One patient also had upper limb proximal muscle weakness and mild tongue and orbicularis oculi muscle weakness. Only one patient also had mild length-dependent sensory predominant peripheral neuropathy. Three patients had elevated creatine kinase (CK), two patients had cardiac involvement, and one had restrictive lung disease with concomitant obstructive lung disease. EMG showed abnormal spontaneous activity and complex repetitive discharges. A myopathic pattern was noted in 4/5 patients combined with neurogenic findings in two patients. 

Muscle biopsy showed fiber degeneration and regeneration and rimmed vacuoles in most. Muscle imaging showed fatty replacement primarily in adductor magnus, vastus intermedius and medialis, and tibialis anterior and medial gastrocnemius. Genetic testing revealed VCP mutations all reported as pathogenic in the literature.

The authors summarize that the findings indicate that VCP gene mutations might lead to a primarily skeletal muscle-related phenotype, without affecting the central nervous system, contrary to some previous reports. Further research is needed to fully comprehend the wide-ranging and distinct clinical phenotypes associated with these mutations.

Comments: This disease affects the peripheral nervous system at multiple levels. This is an intriguing manner that single gene VCP mutation impacts various aspects of the nervous system, encompassing proximal myopathy, distal myopathy, as well as involvement of upper motor neurons.