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.  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 (in 90%), osteolytic bone lesions consistent with Paget disease (in 50%), and frontotemporal dementia (in 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.

Copy number variation (CNV) analysis of the Paget disease of bone and related disorders genes using a high density targeted (HDT) array is also offered as a panel. Additionally, CTGT offers a comprehensive test (both NGS panel and HDT array panel) for these genes. Panel genes are also offered as individual sequencing and deletion/duplication tests, unless otherwise indicated.

The Paget disease of bone and related disorders NGS panel consists of seven genes: HNRNPA1, HNRNPA2B1, SQSTM1, TNFRSF11A, TNFRSF11B, VCP and ZNF687.