IllnessMorbus Paget [of bone], differential diagnosis

NGS +

In Paget's disease, the bone mass increases but becomes weaker with a parallel increase in fracture tendency. The classic form of Paget's disease of the bones typically occurs in middle age or later - usually in one or a few bones. Many people with Paget's disease have no symptoms, and the disease is often diagnosed incidentally. Symptoms include arthritic pain, for example. Other complications depend on which bones are affected. Osteosarcomas develop in less than 1/1 000 patients with Paget's disease. Early-onset Paget's disease is less common, occurring in the teens or twenties. The features are similar to those of the classic form associated with hearing loss at younger age. Three genes are associated with Paget's disease: SQSTM1, TNFRSF11A and TNFRSF11B. Mutations in SQSTM1 are the most common genetic cause, accounting for 10-50% of familial cases and 5-30% of the many patients without family history. All three genes are involved in bone remodelling. In 15-40% of all cases of classic Paget's disease with early onset, the disease shows autosomal dominant inheritance patterns. In the remaining cases, the inheritance is multifactorial. Close relatives of patients with classic Paget's disease have up to a 10-fold higher risk of developing the disease than people without affected relatives. The multifactorial cause of Paget's disease in many disease cases explains the à priori difficulty in assessing the molecular genetic diagnostic yield.

References: https://www.ncbi.nlm.nih.gov/books/NBK1476/

https://www.ncbi.nlm.nih.gov/books/NBK1450

• Alias: Ostitis deformans Paget
• Allelic: Amyotrophic lateral sclerosis 18 (PFN1)
• Allelic: Amyotrophic lateral sclerosis 20 (HNRNPA1)
• Allelic: Amyotrophic lateral sclerosis [MONDO:0004976] (HNRNPA2B1)
• Allelic: Charcot-Marie-Tooth disease, type 2Y (VCP)
• Allelic: Frontotemporal dementia and/or amyotrophic lateral sclerosis 3 (SQSTM1)
• Allelic: Frontotemporal dementia and/or amyotrophic lateral sclerosis 6 (VCP)
• Allelic: Neurodegeneration with ataxia, dystonia, gaze palsy, childhood-onset (SQSTM1)
• Inclusion body myopathy + early-onset Paget disease + frontotemporal dementia 1 (VCP)
• Inclusion body myopathy + early-onset Paget disease with/-out frontotemporal dementia 2 (HNRNPA2B1)
• Inclusion body myopathy + early-onset Paget disease without frontotemporal dementia 3 (HNRNPA1)
• Myopathy, distal, with rimmed vacuoles (SQSTM1)
• Osteolysis, familial expansile (TNFRSF11A)
• Osteopetrosis, AR 7 (TNFRSF11A)
• Paget disease of bone 2, early-onset (TNFRSF11A)
• Paget disease of bone 3 (SQSTM1)
• Paget disease of bone 5, juvenile-onset (TNFRSF11B)
• Paget disease of bone 6 (ZNF687)
• Paget’s disease of bone [MONDO:0005382] (PFN1)