MCID: MLT065
MIFTS: 41

Multicentric Osteolysis, Nodulosis, and Arthropathy

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

Aliases & Classifications for Multicentric Osteolysis, Nodulosis, and Arthropathy

MalaCards integrated aliases for Multicentric Osteolysis, Nodulosis, and Arthropathy:

Name: Multicentric Osteolysis, Nodulosis, and Arthropathy 53 24 71
Torg-Winchester Syndrome 23 24 71 36 13 69
Nodulosis-Arthropathy-Osteolysis Syndrome 53 23 24 55 71
Torg Syndrome 53 23 49 24 71
Nao Syndrome 53 24 55 71 51
Mona 53 49 24 71
Al-Aqeel Sewairi Syndrome 53 24 71
Multicentric Osteolysis, Nodulosis and Arthropathy 49 28
Osteolysis, Hereditary Multicentric 53 49
Hereditary Multicentric Osteolysis 24 71
Multicentric Osteolysis-Nodulosis-Arthropathy Syndrome 55
Multicentric Osteolysis Nodulosis and Arthropathy 23
Nodulosis Arthropathy Osteolysis Syndrome 49
Torg-Winchester Syndrome, Formerly 53
Winchester-Grossman Syndrome 49
Torg Winchester Syndrome 49
Al-Qeel Sewairi Syndrome 49
Winchester Syndrome 49
Noa Syndrome 49

Characteristics:

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
abnormal gait


HPO:

31
multicentric osteolysis, nodulosis, and arthropathy:
Onset and clinical course infantile onset juvenile onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Multicentric Osteolysis, Nodulosis, and Arthropathy

OMIM : 53 Zankl et al. (2007) defined what they considered to be a continuous clinical spectrum involving Torg syndrome, Winchester syndrome (277950), and NAO syndrome. Torg syndrome is characterized by the presence of multiple, painless, subcutaneous nodules and mild to moderate osteoporosis and osteolysis that is usually limited to the hands and feet. Radiographically, the osteolysis is accompanied by a characteristic widening of the metacarpal and metatarsal bones. Winchester syndrome presents with severe osteolysis in the hands and feet and generalized osteoporosis and bone thinning, similar to NAO, but subcutaneous nodules are characteristically absent. Various additional features including coarse face, corneal opacities, gum hypertrophy, and EKG changes have been reported. NAO syndrome, which has only been described in patients from Saudi Arabia, is generally more severe, with multiple prominent and painful subcutaneous nodules, massive osteolysis in the hands and feet, and generalized osteoporosis. Coarse face and body hirsutism are additional features. (259600)

MalaCards based summary : Multicentric Osteolysis, Nodulosis, and Arthropathy, also known as torg-winchester syndrome, is related to winchester syndrome and multicentric carpotarsal osteolysis syndrome, and has symptoms including arthralgia, hypertelorism and frontal bossing. An important gene associated with Multicentric Osteolysis, Nodulosis, and Arthropathy is MMP2 (Matrix Metallopeptidase 2), and among its related pathways/superpathways are Degradation of the extracellular matrix and Development Endothelin-1/EDNRA signaling. The drugs Pamidronate and Zoledronic acid have been mentioned in the context of this disorder. Affiliated tissues include bone and skin.

UniProtKB/Swiss-Prot : 71 Multicentric osteolysis, nodulosis, and arthropathy: An autosomal recessive syndrome characterized by severe multicentric osteolysis with predominant involvement of the hands and feet. Additional features include coarse face, corneal opacities, patches of thickened, hyperpigmented skin, hypertrichosis and gum hypertrophy.

Genetics Home Reference : 24 Multicentric osteolysis, nodulosis, and arthropathy (MONA) describes a rare inherited disease characterized by a loss of bone tissue (osteolysis), particularly in the hands and feet. MONA includes a condition formerly called nodulosis-arthropathy-osteolysis (NAO) syndrome. It may also include a similar disorder called Torg syndrome, although it is unknown whether Torg syndrome is actually part of MONA or a separate disorder caused by a mutation in a different gene.

GeneReviews: NBK373578

Related Diseases for Multicentric Osteolysis, Nodulosis, and Arthropathy

Graphical network of the top 20 diseases related to Multicentric Osteolysis, Nodulosis, and Arthropathy:



Diseases related to Multicentric Osteolysis, Nodulosis, and Arthropathy

Symptoms & Phenotypes for Multicentric Osteolysis, Nodulosis, and Arthropathy

Symptoms via clinical synopsis from OMIM:

53
Skeletal Feet:
pes planus
pes cavus
interphalangeal joint erosions
tarsal osteolysis
widened metatarsal shaft
more
Skeletal Hands:
carpal osteolysis
finger contractures
fusiform finger swelling
interphalangeal joint erosions
widened metacarpal shaft
more
Skeletal Limbs:
flexion contractures (elbows and knees)

Laboratory Abnormalities:
elevated antinuclear antibody (ana) (speckled pattern)
elevated il1-beta
elevated il6

Skeletal:
osteoporosis

Skeletal Pelvis:
flexion contracture (hip)

Skin Nails Hair Skin:
subcutaneous nodules (interphalangeal joints, knees, feet, elbows, pretibial)
hyperpigmented erythematous lesions


Clinical features from OMIM:

259600

Human phenotypes related to Multicentric Osteolysis, Nodulosis, and Arthropathy:

31 (show all 50)
# Description HPO Frequency HPO Source Accession
1 arthralgia 31 HP:0002829
2 hypertelorism 31 HP:0000316
3 frontal bossing 31 HP:0002007
4 osteopenia 31 HP:0000938
5 gait disturbance 31 HP:0001288
6 gingival overgrowth 31 HP:0000212
7 coarse facial features 31 HP:0000280
8 pes planus 31 HP:0001763
9 short stature 31 HP:0004322
10 osteoporosis 31 HP:0000939
11 subcutaneous nodule 31 HP:0001482
12 brachycephaly 31 HP:0000248
13 micrognathia 31 HP:0000347
14 delayed eruption of teeth 31 HP:0000684
15 abnormality of the thorax 31 HP:0000765
16 pes cavus 31 HP:0001761
17 hypoplasia of the maxilla 31 HP:0000327
18 protrusio acetabuli 31 HP:0003179
19 bulbous nose 31 HP:0000414
20 thickened skin 31 HP:0001072
21 split hand 31 HP:0001171
22 proptosis 31 HP:0000520
23 narrow nasal bridge 31 HP:0000446
24 hypermelanotic macule 31 HP:0001034
25 wrist flexion contracture 31 HP:0001239
26 hip contracture 31 HP:0003273
27 kyphoscoliosis 31 HP:0002751
28 antinuclear antibody positivity 31 HP:0003493
29 hirsutism 31 HP:0001007
30 camptodactyly of toe 31 HP:0001836
31 broad metatarsal 31 HP:0001783
32 vertebral compression fractures 31 HP:0002953
33 delayed closure of the anterior fontanelle 31 HP:0001476
34 abnormality of the ear 31 HP:0000598
35 carpal osteolysis 31 HP:0001495
36 metacarpal osteolysis 31 HP:0001504
37 metaphyseal widening 31 HP:0003016
38 ankle contracture 31 HP:0006466
39 metatarsal osteolysis 31 HP:0001473
40 c1-c2 subluxation 31 HP:0003320
41 interphalangeal joint erosions 31 HP:0006252
42 widened metacarpal shaft 31 HP:0006012
43 thin metacarpal cortices 31 HP:0006086
44 thin metatarsal cortices 31 HP:0008078
45 osteolysis involving tarsal bones 31 HP:0006234
46 interphalangeal joint contracture of finger 31 HP:0001220
47 sclerotic cranial sutures 31 HP:0005441
48 peripheral opacification of the cornea 31 HP:0008011
49 ankylosis of feet small joints 31 HP:0008090
50 distal tapering of metatarsals 31 HP:0008133

Drugs & Therapeutics for Multicentric Osteolysis, Nodulosis, and Arthropathy

Drugs for Multicentric Osteolysis, Nodulosis, and Arthropathy (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Pamidronate Approved 40391-99-9 4674
2
Zoledronic acid Approved 118072-93-8 68740
3 Bone Density Conservation Agents
4 Diphosphonates

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Bisphosphonate Therapy in MONA Spectrum Disorder Completed NCT02823925 Pamidronate or Zoledronate

Search NIH Clinical Center for Multicentric Osteolysis, Nodulosis, and Arthropathy

Genetic Tests for Multicentric Osteolysis, Nodulosis, and Arthropathy

Genetic tests related to Multicentric Osteolysis, Nodulosis, and Arthropathy:

# Genetic test Affiliating Genes
1 Multicentric Osteolysis, Nodulosis and Arthropathy 28 MMP2

Anatomical Context for Multicentric Osteolysis, Nodulosis, and Arthropathy

MalaCards organs/tissues related to Multicentric Osteolysis, Nodulosis, and Arthropathy:

38
Bone, Skin

Publications for Multicentric Osteolysis, Nodulosis, and Arthropathy

Articles related to Multicentric Osteolysis, Nodulosis, and Arthropathy:

# Title Authors Year
1
Clinical and mutation profile of multicentric osteolysis nodulosis and arthropathy. ( 26601801 )
2016
2
Functional characterisation of a novel mutation affecting the catalytic domain of MMP2 in siblings with multicentric osteolysis, nodulosis and arthropathy. ( 25273674 )
2014
3
A novel homozygous MMP2 mutation in a patient with Torg-Winchester syndrome. ( 20720557 )
2010
4
Torg-Winchester syndrome: lack of efficacy of pamidronate therapy. ( 17351352 )
2007
5
The new syndrome is not really a new syndrome. Al-Aqeel Sewairi syndrome, a new autosomal recessive disorder with multicentric osteolysis, nodulosis, and arthropathy. ( 16047082 )
2005
6
The new syndrome is not really a new syndrome. Al-Aqeel Sewairi syndrome, a new autosomal recessive disorder with multicentric osteolysis, nodulosis, and arthropathy. ( 16178093 )
2005
7
Multicentric Osteolysis Nodulosis and Arthropathy ( 27413800 )
1993

Variations for Multicentric Osteolysis, Nodulosis, and Arthropathy

UniProtKB/Swiss-Prot genetic disease variations for Multicentric Osteolysis, Nodulosis, and Arthropathy:

71
# Symbol AA change Variation ID SNP ID
1 MMP2 p.Arg101His VAR_032423 rs121912953
2 MMP2 p.Glu404Lys VAR_032425 rs121912955

ClinVar genetic disease variations for Multicentric Osteolysis, Nodulosis, and Arthropathy:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 MMP2 NM_004530.5(MMP2): c.302G> A (p.Arg101His) single nucleotide variant Pathogenic rs121912953 GRCh37 Chromosome 16, 55516969: 55516969
2 MMP2 NM_004530.5(MMP2): c.732C> A (p.Tyr244Ter) single nucleotide variant Pathogenic rs121912954 GRCh37 Chromosome 16, 55519589: 55519589
3 MMP2 NM_004530.5(MMP2): c.1210G> A (p.Glu404Lys) single nucleotide variant Pathogenic rs121912955 GRCh37 Chromosome 16, 55525742: 55525742
4 MMP2 MMP2, 3-BP DEL, 1488TGG deletion Pathogenic
5 MMP2 MMP2, 1-BP DEL, 1357C deletion Pathogenic
6 MMP14 NM_004995.3(MMP14): c.50C> G (p.Thr17Arg) single nucleotide variant Pathogenic rs587777039 GRCh37 Chromosome 14, 23306076: 23306076
7 MMP2 NM_004530.5(MMP2): c.265delC (p.Asp90Thrfs) deletion Pathogenic rs794727275 GRCh37 Chromosome 16, 55516932: 55516932
8 MMP2 NM_004530.5(MMP2): c.1287delG (p.Asn430Thrfs) deletion Pathogenic rs794727916 GRCh37 Chromosome 16, 55525819: 55525819

Expression for Multicentric Osteolysis, Nodulosis, and Arthropathy

Search GEO for disease gene expression data for Multicentric Osteolysis, Nodulosis, and Arthropathy.

Pathways for Multicentric Osteolysis, Nodulosis, and Arthropathy

GO Terms for Multicentric Osteolysis, Nodulosis, and Arthropathy

Cellular components related to Multicentric Osteolysis, Nodulosis, and Arthropathy according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular matrix GO:0031012 8.62 MMP14 MMP2

Biological processes related to Multicentric Osteolysis, Nodulosis, and Arthropathy according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 angiogenesis GO:0001525 9.32 MMP14 MMP2
2 response to hypoxia GO:0001666 9.26 MMP14 MMP2
3 extracellular matrix disassembly GO:0022617 9.16 MMP14 MMP2
4 collagen catabolic process GO:0030574 8.96 MMP14 MMP2
5 endodermal cell differentiation GO:0035987 8.62 MMP14 MMP2

Molecular functions related to Multicentric Osteolysis, Nodulosis, and Arthropathy according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 peptidase activity GO:0008233 9.26 MMP14 MMP2
2 serine-type endopeptidase activity GO:0004252 9.16 MMP14 MMP2
3 metallopeptidase activity GO:0008237 8.96 MMP14 MMP2
4 metalloendopeptidase activity GO:0004222 8.62 MMP14 MMP2

Sources for Multicentric Osteolysis, Nodulosis, and Arthropathy

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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