Test Directory

Paget disease of bone (PDB) is a common metabolic bone disorder characterized by focal and disorganized increases of bone turnover affecting one or more sites throughout the skeleton. Most patients with PDB are asymptomatic but can present with bone pain, osteoarthritis, pathological fracture, bone deformity, deafness, and nerve compression syndromes. PDB2, PDB3, PDB5 and PDB6 are caused by mutations in the TNFRSF11A, SQSTM1, TNFRSF11B and ZNF687 genes, respectively. PDB2 (MIM 602080), PDB3 (MIM 167250) and PDB6 (MIM 616833) are autosomal dominant disorders. The age of onset for PDB3 and PDB6 is usually over 40 years. PDB5 (MIM 239000) is an autosomal recessive disorder. PDB2 and PDB5 have an earlier onset than PDB3 and PDB6. Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia (IBMPFD) is an autosomal dominant disorder characterized by incomplete penetrance of 3 main features: disabling muscle weakness (90%), osteolytic bone lesions consistent with Paget disease (50%), and frontotemporal dementia (30%). The age at onset of muscle weakness and bone disease is between 24 to 61 and 23 to 65 years, respectively.  The mean age at onset of dementia is 57 years.  Mutations in three genes can cause IBMPFD: VCP (IBMPFD1; MIM 167320), HNRPA2B1 (IBMPFD2; MIM 615422) and HNRNPA1 (IBMPFD3; MIM 615424).