MCID: PGT008
MIFTS: 44

Paget Disease of Bone 5, Juvenile-Onset

Categories: Genetic diseases, Rare diseases, Bone diseases, Fetal diseases

Aliases & Classifications for Paget Disease of Bone 5, Juvenile-Onset

MalaCards integrated aliases for Paget Disease of Bone 5, Juvenile-Onset:

Name: Paget Disease of Bone 5, Juvenile-Onset 53 49 71
Hyperostosis Corticalis Deformans Juvenilis 53 49 24 55 71
Juvenile Paget Disease 53 49 24 55 71
Hereditary Hyperphosphatasia 49 55 71 69
Jpd 53 49 24 71
Hyperphosphatasia, Familial Idiopathic 53 49 24
Hyperphosphatasemia with Bone Disease 24 28 69
Hyperphosphatasemia, Chronic Congenital Idiopathic 53 49
Juvenile Paget's Disease 24 55
Paget Disease, Juvenile 13 51
Osteoectasia, Familial 53 71
Familial Osteoectasia 24 55
Pdb5 53 71
Jpg 49 55
Chronic Congenital Idiopathic Hyperphosphatasemia 24
Chronic Congenital Idiopathic Hyperphosphatasia 71
Hyperostosid Corticalis Deformans Juvenilis 49
Familial Idiopathic Hyperphosphatasemia 24
Osteoectasia with Hyperphosphatasia 24
Osteochalasia Desmalis Familiaris 24
Idiopathic Hyperphosphatasia 24
Juvenile Paget Disease; Jpd 53
Paget Disease Juvenile Type 49
Juvenile Pagets Disease 49

Characteristics:

Orphanet epidemiological data:

55
juvenile paget disease
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood; Age of death: normal life expectancy;

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
variable severity
progressive disorder
onset in first decade


HPO:

31
paget disease of bone 5, juvenile-onset:
Onset and clinical course variable expressivity progressive
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Paget Disease of Bone 5, Juvenile-Onset

NIH Rare Diseases : 49 Juvenile Paget disease is a very rare condition that affects bone growth. This condition causes bones to be abnormally large, misshapen, and easily broken (fractured). Signs and symptoms usually appear in infancy or early childhood. As bones grow, they become weaker and more deformed. This condition 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 condition also affects bones of the spine (vertebrae), 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. Juvenile Paget disease is caused by mutations in the TNFRSF11B gene and is inherited in an autosomal recessive fashion. Last updated: 11/3/2015

MalaCards based summary : Paget Disease of Bone 5, Juvenile-Onset, also known as hyperostosis corticalis deformans juvenilis, is related to paget's disease of bone and periodontitis, aggressive, 1, and has symptoms including macrocephaly, hypertension and hearing impairment. An important gene associated with Paget Disease of Bone 5, Juvenile-Onset is TNFRSF11B (TNF Receptor Superfamily Member 11b), and among its related pathways/superpathways are Development Endothelin-1/EDNRA signaling and TRAF Pathway. Affiliated tissues include bone, and related phenotype is limbs/digits/tail.

OMIM : 53 Paget disease of bone-5 is an autosomal recessive, juvenile-onset form of Paget disease, a disorder of the skeleton resulting from abnormal bone resorption and formation. Clinical manifestations include short stature, progressive long bone deformities, fractures, vertebral collapse, skull enlargement, and hyperostosis with progressive deafness. There is phenotypic variability, with some patients presenting in infancy, while others present later in childhood (summary by Naot et al., 2014). For discussion of genetic heterogeneity of Paget disease of bone, see 167250. (239000)

UniProtKB/Swiss-Prot : 71 Paget disease of bone 5, juvenile-onset: An autosomal recessive, juvenile-onset form of Paget disease, a disorder of bone remodeling characterized by increased bone turnover affecting one or more sites throughout the skeleton, primarily the axial skeleton. Osteoclastic overactivity followed by compensatory osteoblastic activity leads to a structurally disorganized mosaic of bone (woven bone), which is mechanically weaker, larger, less compact, more vascular, and more susceptible to fracture than normal adult lamellar bone. PDB5 clinical manifestations include short stature, progressive long bone deformities, fractures, vertebral collapse, skull enlargement, and hyperostosis with progressive deafness.

Genetics Home Reference : 24 Juvenile Paget disease is a disorder that affects bone growth. This disease causes bones to be abnormally large, misshapen, and easily broken (fractured).

Related Diseases for Paget Disease of Bone 5, Juvenile-Onset

Diseases related to Paget Disease of Bone 5, Juvenile-Onset via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 47)
# Related Disease Score Top Affiliating Genes
1 paget's disease of bone 30.3 CALCA TNFRSF11A TNFRSF11B TNFSF11
2 periodontitis, aggressive, 1 11.2
3 fibrogenesis imperfecta ossium 10.1 CALCA TNFRSF11B
4 secondary hyperparathyroidism of renal origin 10.1 CALCA TNFRSF11B
5 renal osteodystrophy 10.1 CALCA TNFRSF11B
6 periostitis 10.0 TNFRSF11A TNFRSF11B
7 giant cell reparative granuloma 10.0 CALCA TNFRSF11A
8 hypercalcemia, infantile, 1 9.9
9 hyperparathyroidism 9.9 CALCA TNFRSF11B
10 multicentric reticulohistiocytosis 9.9 TNFRSF11B TNFSF11
11 kummell's disease 9.9 TNFRSF11B TNFSF11
12 periodontitis, chronic 9.9 TNFRSF11B TNFSF11
13 chronic apical periodontitis 9.9 TNFRSF11B TNFSF11
14 endosteal hyperostosis, autosomal dominant 9.8 TNFRSF11B TNFSF11
15 osteonecrosis 9.8 TNFRSF11B TNFSF11
16 spondyloarthropathy 1 9.8 TNFRSF11B TNFSF11
17 breast leiomyosarcoma 9.8 TNFRSF11A TNFSF11
18 cholesteatoma 9.8 TNFRSF11B TNFSF11
19 bone inflammation disease 9.8 TNFRSF11B TNFSF11
20 aortic valve disease 2 9.8 TNFRSF11B TNFSF11
21 aneurysm 9.8
22 synovitis 9.8 TNFRSF11B TNFSF11
23 periodontitis 9.7 TNFRSF11B TNFSF11
24 arthropathy 9.7 TNFRSF11B TNFSF11
25 bone cancer 9.7 TNFRSF11A TNFSF11
26 myeloma, multiple 9.6 TNFRSF11B TNFSF11
27 osteopetrosis 9.6 TNFRSF11A TNFSF11
28 psoriatic arthritis 9.6 TNFRSF11B TNFSF11
29 osteogenic sarcoma 9.5 TNFRSF11B TNFSF11
30 glucocorticoid-induced osteoporosis 9.5 CALCA TNFRSF11B TNFSF11
31 polyarticular onset juvenile idiopathic arthritis 9.4 TNFRSF11A TNFRSF11B TNFSF11
32 hemophilic arthropathy 9.4 TNFRSF11A TNFRSF11B TNFSF11
33 familial expansile osteolysis 9.4 TNFRSF11A TNFRSF11B TNFSF11
34 cohen-gibson syndrome 9.4 TNFRSF11A TNFRSF11B TNFSF11
35 multicentric carpotarsal osteolysis syndrome 9.4 TNFRSF11A TNFRSF11B TNFSF11
36 aneurysmal bone cysts 9.4 CALCA TNFRSF11A TNFSF11
37 periapical periodontitis 9.4 TNFRSF11A TNFRSF11B TNFSF11
38 tooth resorption 9.4 TNFRSF11A TNFRSF11B TNFSF11
39 ischemic bone disease 9.4 TNFRSF11A TNFRSF11B TNFSF11
40 periodontal disease 9.4 TNFRSF11A TNFRSF11B TNFSF11
41 osteoarthritis 9.4 TNFRSF11B TNFSF11
42 rheumatoid arthritis 9.3 TNFRSF11A TNFRSF11B TNFSF11
43 root resorption 9.1 CALCA TNFRSF11A TNFRSF11B TNFSF11
44 bone resorption disease 9.1 CALCA TNFRSF11A TNFRSF11B TNFSF11
45 bone remodeling disease 9.1 CALCA TNFRSF11A TNFRSF11B TNFSF11
46 giant cell tumor 9.1 CALCA TNFRSF11A TNFRSF11B TNFSF11
47 osteoporosis 9.0 CALCA TNFRSF11A TNFRSF11B TNFSF11

Graphical network of the top 20 diseases related to Paget Disease of Bone 5, Juvenile-Onset:



Diseases related to Paget Disease of Bone 5, Juvenile-Onset

Symptoms & Phenotypes for Paget Disease of Bone 5, Juvenile-Onset

Symptoms via clinical synopsis from OMIM:

53
SkeletalSpine:
kyphosis
ankylosis

GrowthHeight:
short stature

HeadAndNeckEars:
hearing loss, sensorineural

ChestExternalFeatures:
barrel chest

HeadAndNeckEyes:
angioid streaks (in some patients)
retinopathy (in some patients)
macular scarring (in some patients)

SkeletalLimbs:
bowing of the long bones
deformities of the long bones

Skeletal:
osteoporosis
osteosclerosis
increased fractures
paget disease of bone
demineralization

LaboratoryAbnormalities:
increased serum alkaline phosphatase

NeurologicCentralNervousSystem:
delayed motor development (in some patients)

SkeletalSkull:
thickening of the skull
skull expansion


Clinical features from OMIM:

239000

Human phenotypes related to Paget Disease of Bone 5, Juvenile-Onset:

55 31 (show all 35)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 macrocephaly 55 31 hallmark (90%) Very frequent (99-80%) HP:0000256
2 hypertension 55 31 frequent (33%) Frequent (79-30%) HP:0000822
3 hearing impairment 55 31 frequent (33%) Frequent (79-30%) HP:0000365
4 bowing of the long bones 55 31 hallmark (90%) Very frequent (99-80%) HP:0006487
5 abnormality of the dentition 55 31 hallmark (90%) Very frequent (99-80%) HP:0000164
6 pectus carinatum 55 31 frequent (33%) Frequent (79-30%) HP:0000768
7 optic atrophy 55 31 frequent (33%) Frequent (79-30%) HP:0000648
8 short stature 55 31 hallmark (90%) Very frequent (99-80%) HP:0004322
9 abnormality of retinal pigmentation 55 31 frequent (33%) Frequent (79-30%) HP:0007703
10 osteoporosis 55 31 hallmark (90%) Very frequent (99-80%) HP:0000939
11 subcutaneous nodule 55 31 occasional (7.5%) Occasional (29-5%) HP:0001482
12 hyperuricemia 55 31 hallmark (90%) Very frequent (99-80%) HP:0002149
13 melanocytic nevus 55 31 occasional (7.5%) Occasional (29-5%) HP:0000995
14 recurrent fractures 55 31 hallmark (90%) Very frequent (99-80%) HP:0002757
15 abnormality of the clavicle 55 31 hallmark (90%) Very frequent (99-80%) HP:0000889
16 rough bone trabeculation 55 31 hallmark (90%) Very frequent (99-80%) HP:0100670
17 cranial hyperostosis 55 31 hallmark (90%) Very frequent (99-80%) HP:0004437
18 muscle weakness 31 HP:0001324
19 kyphosis 31 HP:0002808
20 thickened calvaria 31 HP:0002684
21 sensorineural hearing impairment 31 HP:0000407
22 retinopathy 31 occasional (7.5%) HP:0000488
23 increased bone mineral density 31 HP:0011001
24 motor delay 31 occasional (7.5%) HP:0001270
25 barrel-shaped chest 31 HP:0001552
26 elevated alkaline phosphatase 31 HP:0003155
27 premature loss of teeth 31 HP:0006480
28 retinal degeneration 31 occasional (7.5%) HP:0000546
29 hyperphosphatemia 31 HP:0002905
30 elevated serum acid phosphatase 31 HP:0003148
31 hydroxyprolinemia 31 HP:0003260
32 ankylosis 31 HP:0031013
33 hydroxyprolinuria 31 HP:0003080
34 macular scar 31 occasional (7.5%) HP:0200056
35 angioid streaks of the fundus 31 HP:0001102

MGI Mouse Phenotypes related to Paget Disease of Bone 5, Juvenile-Onset:

43
# Description MGI Source Accession Score Top Affiliating Genes
1 limbs/digits/tail MP:0005371 8.8 TNFRSF11A TNFRSF11B TNFSF11

Drugs & Therapeutics for Paget Disease of Bone 5, Juvenile-Onset

Search Clinical Trials , NIH Clinical Center for Paget Disease of Bone 5, Juvenile-Onset

Genetic Tests for Paget Disease of Bone 5, Juvenile-Onset

Genetic tests related to Paget Disease of Bone 5, Juvenile-Onset:

# Genetic test Affiliating Genes
1 Hyperphosphatasemia with Bone Disease 28 TNFRSF11B

Anatomical Context for Paget Disease of Bone 5, Juvenile-Onset

MalaCards organs/tissues related to Paget Disease of Bone 5, Juvenile-Onset:

38
Bone

Publications for Paget Disease of Bone 5, Juvenile-Onset

Articles related to Paget Disease of Bone 5, Juvenile-Onset:

# Title Authors Year
1
Genotype-phenotype correlation in juvenile Paget disease: role of molecular alterations of the TNFRSF11B gene. ( 22638612 )
2012
2
Bilateral cavernous internal carotid aneurysms in a child with juvenile paget disease and osteoprotegerin deficiency. ( 17947367 )
2008

Variations for Paget Disease of Bone 5, Juvenile-Onset

ClinVar genetic disease variations for Paget Disease of Bone 5, Juvenile-Onset:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 TNFRSF11B NC_000008.11: g.118920356_119017859del97504 deletion Pathogenic GRCh38 Chromosome 8, 118920356: 119017859
2 TNFRSF11B NM_002546.3(TNFRSF11B): c.544_546delGAC (p.Asp182del) deletion Pathogenic rs796051868 GRCh37 Chromosome 8, 119941023: 119941025
3 TNFRSF11B NM_002546.3(TNFRSF11B): c.260G> A (p.Cys87Tyr) single nucleotide variant Pathogenic rs104894091 GRCh37 Chromosome 8, 119945310: 119945310
4 TNFRSF11B NM_002546.3(TNFRSF11B): c.349T> C (p.Phe117Leu) single nucleotide variant Pathogenic rs104894092 GRCh37 Chromosome 8, 119945221: 119945221
5 TNFRSF11B TNFRSF11B, 3-BP DEL AND 2-BP INS indel Pathogenic
6 TNFRSF11B TNFRSF11B, 245-KB DEL deletion Pathogenic
7 TNFRSF11B NM_002546.3(TNFRSF11B): c.226A> C (p.Thr76Pro) single nucleotide variant Pathogenic rs200071478 GRCh37 Chromosome 8, 119945344: 119945344

Expression for Paget Disease of Bone 5, Juvenile-Onset

Search GEO for disease gene expression data for Paget Disease of Bone 5, Juvenile-Onset.

Pathways for Paget Disease of Bone 5, Juvenile-Onset

Pathways related to Paget Disease of Bone 5, Juvenile-Onset according to GeneCards Suite gene sharing:

(show all 12)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.16 TNFRSF11A TNFRSF11B TNFSF11
2
Show member pathways
12.14 TNFRSF11A TNFRSF11B TNFSF11
3
Show member pathways
11.94 TNFRSF11A TNFRSF11B TNFSF11
4 11.78 TNFRSF11A TNFSF11
5 11.54 TNFRSF11A TNFRSF11B TNFSF11
6 11.47 TNFRSF11A TNFSF11
7 11.43 TNFRSF11A TNFSF11
8
Show member pathways
11.32 TNFRSF11A TNFSF11
9
Show member pathways
11.25 TNFRSF11A TNFRSF11B TNFSF11
10 10.58 CALCA TNFRSF11A TNFRSF11B TNFSF11
11 10.47 TNFRSF11B TNFSF11
12 10.34 TNFRSF11A TNFRSF11B TNFSF11

GO Terms for Paget Disease of Bone 5, Juvenile-Onset

Biological processes related to Paget Disease of Bone 5, Juvenile-Onset according to GeneCards Suite gene sharing:

(show all 15)
# Name GO ID Score Top Affiliating Genes
1 regulation of receptor activity GO:0010469 9.65 CALCA TNFRSF11B TNFSF11
2 inflammatory response GO:0006954 9.63 CALCA TNFRSF11A TNFRSF11B
3 response to lipopolysaccharide GO:0032496 9.55 TNFRSF11A TNFRSF11B
4 positive regulation of NF-kappaB transcription factor activity GO:0051092 9.54 TNFRSF11A TNFSF11
5 positive regulation of DNA binding transcription factor activity GO:0051091 9.52 TNFRSF11A TNFSF11
6 ossification GO:0001503 9.51 TNFRSF11A TNFSF11
7 tumor necrosis factor-mediated signaling pathway GO:0033209 9.5 TNFRSF11A TNFRSF11B TNFSF11
8 apoptotic signaling pathway GO:0097190 9.49 TNFRSF11A TNFRSF11B
9 osteoclast differentiation GO:0030316 9.43 TNFRSF11A TNFSF11
10 mammary gland alveolus development GO:0060749 9.4 TNFRSF11A TNFSF11
11 negative regulation of bone resorption GO:0045779 9.37 CALCA TNFRSF11B
12 TNFSF11-mediated signaling pathway GO:0071847 9.26 TNFRSF11A TNFSF11
13 positive regulation of fever generation by positive regulation of prostaglandin secretion GO:0071812 9.16 TNFRSF11A TNFSF11
14 positive regulation of ERK1 and ERK2 cascade via TNFSF11-mediated signaling GO:0071848 8.96 TNFRSF11A TNFSF11
15 monocyte chemotaxis GO:0002548 8.8 CALCA TNFRSF11A TNFSF11

Molecular functions related to Paget Disease of Bone 5, Juvenile-Onset according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 tumor necrosis factor-activated receptor activity GO:0005031 8.62 TNFRSF11A TNFRSF11B

Sources for Paget Disease of Bone 5, Juvenile-Onset

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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