Encyclopedia
Juvenile Paget disease is a disorder that affects bone growth. This disease causes bones to be abnormally large, misshapen, and easily broken (fractured).
- genetic conditions
1. Introduction
The signs of juvenile Paget disease appear in infancy or early childhood. As bones grow, they become progressively weaker and more deformed. These abnormalities usually become more severe during the adolescent growth spurt, when bones grow very quickly.
Juvenile Paget disease affects the entire skeleton, resulting in widespread bone and joint pain. The bones of the skull tend to grow unusually large and thick, which can lead to hearing loss. The disease also affects bones of the spine (vertebrae). The deformed vertebrae can collapse, leading to abnormal curvature of the spine. Additionally, weight-bearing long bones in the legs tend to bow and fracture easily, which can interfere with standing and walking.
2. Frequency
Juvenile Paget disease is rare; about 50 affected individuals have been identified worldwide.
3. Causes
Juvenile Paget disease is caused by mutations in the TNFRSF11B gene. This gene provides instructions for making a protein that is involved in bone remodeling, a normal process in which old bone is broken down and new bone is created to replace it.
Bones are constantly being remodeled, and the process is carefully controlled to ensure that bones stay strong and healthy. Mutations in the TNFRSF11B gene lead to a much faster rate of bone remodeling starting early in life. Bone tissue is broken down more quickly than usual, and when new bone tissue grows it is larger, weaker, and less organized than normal bone. This abnormally fast bone remodeling underlies the problems with bone growth characteristic of juvenile Paget disease.
4. Inheritance
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
5. Other Names for This Condition
-
chronic congenital idiopathic hyperphosphatasemia
-
familial idiopathic hyperphosphatasemia
-
familial osteoectasia
-
hyperostosis corticalis deformans juvenilis
-
hyperphosphatasemia with bone disease
-
hyperphosphatasia, familial idiopathic
-
idiopathic hyperphosphatasia
-
JPD
-
juvenile Paget's disease
-
osteochalasia desmalis familiaris
-
osteoectasia with hyperphosphatasia
This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/condition/juvenile-paget-disease
References
- Chong B, Hegde M, Fawkner M, Simonet S, Cassinelli H, Coker M, Kanis J, SeidelJ, Tau C, Tüysüz B, Yüksel B, Love D; International HyperphosphatasiaCollaborative Group. Idiopathic hyperphosphatasia and TNFRSF11B mutations:relationships between phenotype and genotype. J Bone Miner Res. 2003Dec;18(12):2095-104.
- Cundy T, Hegde M, Naot D, Chong B, King A, Wallace R, Mulley J, Love DR,Seidel J, Fawkner M, Banovic T, Callon KE, Grey AB, Reid IR, Middleton-Hardie CA,Cornish J. A mutation in the gene TNFRSF11B encoding osteoprotegerin causes anidiopathic hyperphosphatasia phenotype. Hum Mol Genet. 2002 Sep 1;11(18):2119-27.
- Cundy T. Idiopathic hyperphosphatasia. Semin Musculoskelet Radiol. 2002Dec;6(4):307-12. Review.
- Daroszewska A, Ralston SH. Mechanisms of disease: genetics of Paget's disease of bone and related disorders. Nat Clin Pract Rheumatol. 2006 May;2(5):270-7.Review.
- Janssens K, de Vernejoul MC, de Freitas F, Vanhoenacker F, Van Hul W. Anintermediate form of juvenile Paget's disease caused by a truncating TNFRSF11Bmutation. Bone. 2005 Mar;36(3):542-8.
- Lucas GJ, Daroszewska A, Ralston SH. Contribution of genetic factors to thepathogenesis of Paget's disease of bone and related disorders. J Bone Miner Res. 2006 Dec;21 Suppl 2:P31-7. Review.
- Ralston SH. Juvenile Paget's disease, familial expansile osteolysis and other genetic osteolytic disorders. Best Pract Res Clin Rheumatol. 2008Mar;22(1):101-11. doi: 10.1016/j.berh.2007.11.005. Review.
- Whyte MP, Obrecht SE, Finnegan PM, Jones JL, Podgornik MN, McAlister WH, Mumm S. Osteoprotegerin deficiency and juvenile Paget's disease. N Engl J Med. 2002Jul 18;347(3):175-84.
