Inclusion body myopathy with Paget disease of bone and frontotemporal dementia (Q102553)

Autosomal dominantly inherited multisystem degenerative disorder caused by mutations in p97/VCP (valosin-containing protein). Myopathy is present in 90%of affected individuals, characterised by adult-onset, proximal and distal muscle weakness with associated atrophy. Affected skeletal muscle contains “rimmed vacuoles” and both myonuclear and sarcoplasmic inclusions. The penetrance of fronto-temporal dementia is approximately 30% and its onset is at a later age than myopathy. CNS tissue has prominent intranuclear ubiquitinated and TDP-43-positive inclusions. Paget disease of the bone manifests in approximately 50% of patients at a similar age to the myopathy. Pagetoid osteoclasts have ubiquitinated nuclear and cytosolic inclusions as well.