Disease Information for Pagets disease, juvenile

Bakwin-Eiger syndrome; Juvenile Paget"s disease; Synonyms:

Chronic hyperphosphatasia, chronic idiopathic; hyperphosphatasia, chronic osteopathy-hyperphosphatasia syndrome, familial osteoectasia, familial osteoectasia-macrocranium syndrome, hereditary hyperphosphatasia, hyperostosis corticalis deformans juvenilis, hyperphosphatasia-osteoectasia syndrome, hyperostosis corticalis deformans juvenilis, infantile hyperphosphatasia, osteoectasia with macrocranium, osteochalasia desmalis familiaris, osteoectasia-hyperphosphatasia syndrome; Hereditary skeletal dysplasia affecting both sexes with characteristic cortical hyperplasia, macrocrania and hyperphosphatasis; Also elevated uric acid, and aminopeptidase, and urinary peptide-bound hydroxyproline and uric acid; The symptoms appear in late infancy and consist of growth deficiency, enlarging of head, hearing loss due to nerve compression, angioid streaks of the retina, optic atrophy, hypertension, blue sclerae, dental caries, fusiform swelling and bowing of the tubular bones and, occasionally, multiple fractures; Demineralisation and osteoporosis may be very severe in some cases and mild in others; Usually, normal intelligence; Autosomal recessively inheritable disturbance with considerable intrafamilial variability of expression; [Whonamedit_com 2005] ---------------------------------------------Paget"s disease of bone is a chronic, slowly progressive skeletal condition of abnormally rapid bone destruction (osteolytic) and reformation (osteoblastic); The new bone may occur in one or more regions of the body and is structurally abnormal, dense and fragile; This abnormal development may cause bone pain, arthritis, deformities and fractures; The bones most frequently affected are in the spine, skull, pelvis and lower legs; The exact cause of Paget’s disease is not known;----------[NORD 2005]---------------------------- Background Juvenile Paget"s disease, an autosomal recessive osteopathy, is characterized by rapidly remodeling woven bone, osteopenia, fractures, and progressive skeletal deformity; Cases: Methods We evaluated two apparently unrelated Navajo patients with juvenile Paget"s disease for defects in the gene encoding osteoprotegerin (TNFRSF11B) using polymerase-chain-reaction (PCR) amplification followed by direct sequencing and Southern blotting of genomic DNA; Genetic markers near TNFRSF11B were evaluated by both a PCR method that involved sequence-tagged site-content mapping of a deletion of TNFRSF11B and PCR spanning the DNA break points; Results Both patients had a homozygous deletion of TNFRSF11B, with identical break points, on chromosome 8q24-2; The defect spans approximately 100 kb, but neighboring genes are intact; We found that serum levels of osteoprotegerin and soluble osteoclast differentiation factor were undetectable and markedly increased, respectively; Conclusions: Juvenile Paget"s disease can result from osteoprotegerin deficiency caused by homozygous deletion of TNFRSF11B; [NEJM 2002]

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