MCID: MLT065
MIFTS: 43

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 57 25 75 37
Nodulosis-Arthropathy-Osteolysis Syndrome 57 24 25 59 75
Torg-Winchester Syndrome 24 25 75 13 73
Torg Syndrome 57 24 53 25 75
Nao Syndrome 57 25 59 75 55
Mona 57 53 25 75
Multicentric Osteolysis, Nodulosis and Arthropathy 53 29 6
Al-Aqeel Sewairi Syndrome 57 25 75
Osteolysis, Hereditary Multicentric 57 53
Hereditary Multicentric Osteolysis 25 75
Torg Winchester Syndrome 53 40
Multicentric Osteolysis-Nodulosis-Arthropathy Syndrome 59
Multicentric Osteolysis Nodulosis and Arthropathy 24
Nodulosis Arthropathy Osteolysis Syndrome 53
Torg-Winchester Syndrome, Formerly 57
Winchester-Grossman Syndrome 53
Al-Qeel Sewairi Syndrome 53
Winchester Syndrome 53
Noa Syndrome 53

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
abnormal gait


HPO:

32
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 : 57 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 nodulosis-arthropathy-osteolysis syndrome, is related to winchester syndrome and multicentric carpotarsal osteolysis syndrome. 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, and related phenotypes are hypertelorism and frontal bossing

Genetics Home Reference : 25 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.

UniProtKB/Swiss-Prot : 75 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.

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:

57
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:

32 (show all 50)
# Description HPO Frequency HPO Source Accession
1 hypertelorism 32 HP:0000316
2 frontal bossing 32 HP:0002007
3 osteopenia 32 HP:0000938
4 gait disturbance 32 HP:0001288
5 gingival overgrowth 32 HP:0000212
6 coarse facial features 32 HP:0000280
7 pes planus 32 HP:0001763
8 short stature 32 HP:0004322
9 osteoporosis 32 HP:0000939
10 subcutaneous nodule 32 HP:0001482
11 arthralgia 32 HP:0002829
12 brachycephaly 32 HP:0000248
13 micrognathia 32 HP:0000347
14 delayed eruption of teeth 32 HP:0000684
15 abnormality of the thorax 32 HP:0000765
16 pes cavus 32 HP:0001761
17 hypoplasia of the maxilla 32 HP:0000327
18 protrusio acetabuli 32 HP:0003179
19 bulbous nose 32 HP:0000414
20 thickened skin 32 HP:0001072
21 split hand 32 HP:0001171
22 proptosis 32 HP:0000520
23 narrow nasal bridge 32 HP:0000446
24 hypermelanotic macule 32 HP:0001034
25 wrist flexion contracture 32 HP:0001239
26 hip contracture 32 HP:0003273
27 kyphoscoliosis 32 HP:0002751
28 antinuclear antibody positivity 32 HP:0003493
29 hirsutism 32 HP:0001007
30 camptodactyly of toe 32 HP:0001836
31 broad metatarsal 32 HP:0001783
32 vertebral compression fractures 32 HP:0002953
33 delayed closure of the anterior fontanelle 32 HP:0001476
34 abnormality of the ear 32 HP:0000598
35 carpal osteolysis 32 HP:0001495
36 metacarpal osteolysis 32 HP:0001504
37 metaphyseal widening 32 HP:0003016
38 ankle contracture 32 HP:0006466
39 metatarsal osteolysis 32 HP:0001473
40 c1-c2 subluxation 32 HP:0003320
41 interphalangeal joint erosions 32 HP:0006252
42 widened metacarpal shaft 32 HP:0006012
43 thin metacarpal cortices 32 HP:0006086
44 thin metatarsal cortices 32 HP:0008078
45 osteolysis involving tarsal bones 32 HP:0006234
46 interphalangeal joint contracture of finger 32 HP:0001220
47 sclerotic cranial sutures 32 HP:0005441
48 peripheral opacification of the cornea 32 HP:0008011
49 ankylosis of feet small joints 32 HP:0008090
50 distal tapering of metatarsals 32 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 29 MMP2

Anatomical Context for Multicentric Osteolysis, Nodulosis, and Arthropathy

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

41
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. ( 16178093 )
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. ( 16047082 )
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:

75
# 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
(show all 14)
# 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.302G> A (p.Arg101His) single nucleotide variant Pathogenic rs121912953 GRCh38 Chromosome 16, 55483057: 55483057
3 MMP2 NM_004530.5(MMP2): c.732C> A (p.Tyr244Ter) single nucleotide variant Pathogenic rs121912954 GRCh37 Chromosome 16, 55519589: 55519589
4 MMP2 NM_004530.5(MMP2): c.732C> A (p.Tyr244Ter) single nucleotide variant Pathogenic rs121912954 GRCh38 Chromosome 16, 55485677: 55485677
5 MMP2 NM_004530.5(MMP2): c.1210G> A (p.Glu404Lys) single nucleotide variant Pathogenic rs121912955 GRCh37 Chromosome 16, 55525742: 55525742
6 MMP2 NM_004530.5(MMP2): c.1210G> A (p.Glu404Lys) single nucleotide variant Pathogenic rs121912955 GRCh38 Chromosome 16, 55491830: 55491830
7 MMP2 MMP2, 3-BP DEL, 1488TGG deletion Pathogenic
8 MMP2 MMP2, 1-BP DEL, 1357C deletion Pathogenic
9 MMP2 NM_004530.5(MMP2): c.265delC (p.Asp90Thrfs) deletion Pathogenic rs794727275 GRCh37 Chromosome 16, 55516932: 55516932
10 MMP2 NM_004530.5(MMP2): c.265delC (p.Asp90Thrfs) deletion Pathogenic rs794727275 GRCh38 Chromosome 16, 55483020: 55483020
11 MMP2 NM_004530.5(MMP2): c.1287delG (p.Asn430Thrfs) deletion Pathogenic rs794727916 GRCh37 Chromosome 16, 55525819: 55525819
12 MMP2 NM_004530.5(MMP2): c.1287delG (p.Asn430Thrfs) deletion Pathogenic rs794727916 GRCh38 Chromosome 16, 55491907: 55491907
13 MMP2 NM_004530.5(MMP2): c.539A> T (p.Asp180Val) single nucleotide variant Uncertain significance rs1057518712 GRCh37 Chromosome 16, 55519220: 55519220
14 MMP2 NM_004530.5(MMP2): c.539A> T (p.Asp180Val) single nucleotide variant Uncertain significance rs1057518712 GRCh38 Chromosome 16, 55485308: 55485308

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
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
Content
Loading form....