TY - JOUR
T1 - Familial Paget's disease of bone: Long-term follow-up of unaffected relatives with and without Sequestosome 1 mutations
AU - Peeters, Joséphine J. M.
AU - de Ridder, Raphaël
AU - Hamoen, Esther C.
AU - Eekhoff, E. Marelise W.
AU - Smit, Frits
AU - Boudin, Eveline
AU - van Hul, Wim
AU - Papapoulos, Socrates E.
AU - Appelman-Dijkstra, Natasha M.
PY - 2019
Y1 - 2019
N2 - Objective: Familial Paget's disease of bone is inherited as an autosomal-dominant trait and mutations in the sequestosome 1 (SQSTM1) gene have been reported with variable frequency in patients with familial disease. The natural history, however, of the disease in family members with or without SQSTM1 mutations is unknown. Methods: To address this question, we investigated members of families with Paget's disease identified and genotyped in 2000 in The Netherlands without clinical, biochemical or radiological signs of Paget's disease. Seventy-five subjects, median age 56 years (range 44–93), with or without SQSTM1 mutations participated in the present study. Medical history was obtained and clinical examination and laboratory investigations were performed in all. When serum biochemical markers of bone turnover were increased, skeletal scintigraphy with SPECT-CT was performed. Results: After a mean period of 15.9 ± 0.32 (SD) years no subject without SQSTM1 mutations (either from positive or negative families) developed Paget's disease. Of 14 carriers of SQSTM1 mutations, Paget's disease of the pelvis was diagnosed in a 74-year old asymptomatic woman. Conclusion: The incidence of new Paget's disease in SQSTM1 positive subjects was 7.1% and no mutation-negative subject developed the disease within 16 years of follow-up. Subjects without SQSTM1 mutations can be reassured whereas mutation carriers should consider screening. Our findings should be confirmed in other populations as currently unknown environmental factors that might be involved in the development of the disease may differ.
AB - Objective: Familial Paget's disease of bone is inherited as an autosomal-dominant trait and mutations in the sequestosome 1 (SQSTM1) gene have been reported with variable frequency in patients with familial disease. The natural history, however, of the disease in family members with or without SQSTM1 mutations is unknown. Methods: To address this question, we investigated members of families with Paget's disease identified and genotyped in 2000 in The Netherlands without clinical, biochemical or radiological signs of Paget's disease. Seventy-five subjects, median age 56 years (range 44–93), with or without SQSTM1 mutations participated in the present study. Medical history was obtained and clinical examination and laboratory investigations were performed in all. When serum biochemical markers of bone turnover were increased, skeletal scintigraphy with SPECT-CT was performed. Results: After a mean period of 15.9 ± 0.32 (SD) years no subject without SQSTM1 mutations (either from positive or negative families) developed Paget's disease. Of 14 carriers of SQSTM1 mutations, Paget's disease of the pelvis was diagnosed in a 74-year old asymptomatic woman. Conclusion: The incidence of new Paget's disease in SQSTM1 positive subjects was 7.1% and no mutation-negative subject developed the disease within 16 years of follow-up. Subjects without SQSTM1 mutations can be reassured whereas mutation carriers should consider screening. Our findings should be confirmed in other populations as currently unknown environmental factors that might be involved in the development of the disease may differ.
KW - Familial
KW - Follow-up
KW - Paget's disease of bone
KW - SQSTM1
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85071413817&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31449886
U2 - https://doi.org/10.1016/j.bone.2019.115044
DO - https://doi.org/10.1016/j.bone.2019.115044
M3 - Article
C2 - 31449886
SN - 8756-3282
VL - 128
JO - Bone
JF - Bone
M1 - 115044
ER -