This report describes general characteristics of the group of diseases classified as inclusion body myopathy with Paget disease of bone and frontotemporal dementia (IBMPFD). IBMPFD is an autosomal dominant disorder, with multiple genes and mapped loci. A listing of IBMPFD subtypes, as defined by OMIM, may be found in the table below, with links to more detailed reports for subtypes that have been investigated using fly models.
[updated May 2016 by FlyBase; FBrf0222196]
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. [from GeneReviews, Inclusion Body Myopathy with Paget Disease of Bone and/or Frontotemporal Dementia, pubmed:20301649 2016.06.03]
IBMPFD is a autosomal dominant disorder linked to multiple genes, characterized by incomplete penetrance of 3 main features: disabling muscle weakness (in 90%), osteolytic bone lesions consistent with Paget disease (in 51%), and frontotemporal dementia (in 32%). Muscle weakness is an isolated symptom in about 30% of patients and the presenting symptom in greater than half of patients, suggesting that IBMPFD may commonly be seen in a neuromuscular clinic without its other syndromic features (review by Weihl et al., 2009, pubmed:19380227). [From MIM:167320, 2016.06.03]
Most cases of IBMPFD are caused by heterozygous mutation in the VCP gene, while a small number of cases have been associated with heterozygous mutation in the HNRNPA1 or HNRNPA2B1 genes. [From MIM:167320, 2016.06.03]