WNCHRS
MCID: WNC001
MIFTS: 36

Winchester Syndrome (WNCHRS)

Categories: Bone diseases, Genetic diseases, Rare diseases, Skin diseases

Aliases & Classifications for Winchester Syndrome

MalaCards integrated aliases for Winchester Syndrome:

Name: Winchester Syndrome 56 74 52 25 73 36 29 6
Wnchrs 56 25 73
Winchester Disease 52 25
Winchester-Grossman Syndrome 52
Syndrome, Winchester 39

Classifications:



Summaries for Winchester Syndrome

Genetics Home Reference : 25 Winchester syndrome is a rare inherited disease characterized by a loss of bone tissue (osteolysis), particularly in the hands and feet. Winchester syndrome used to be considered part of a related condition now called multicentric osteolysis, nodulosis, and arthropathy (MONA). However, because Winchester syndrome and MONA are caused by mutations in different genes, they are now thought to be separate disorders. In most cases of Winchester syndrome, bone loss begins in the hands and feet, causing pain and limiting movement. Bone abnormalities later spread to other parts of the body, with joint problems (arthropathy) occurring in the elbows, shoulders, knees, hips, and spine. Most people with Winchester syndrome develop low bone mineral density (osteopenia) and thinning of the bones (osteoporosis) throughout the skeleton. These abnormalities make bones brittle and more prone to fracture. The bone abnormalities also lead to short stature. Some people with Winchester syndrome have skin abnormalities including patches of dark, thick, and leathery skin. Other features of the condition can include clouding of the clear front covering of the eye (corneal opacity), excess hair growth (hypertrichosis), overgrowth of the gums, heart abnormalities, and distinctive facial features that are described as "coarse."

MalaCards based summary : Winchester Syndrome, also known as wnchrs, is related to multicentric osteolysis-nodulosis-arthropathy spectrum and multicentric osteolysis, nodulosis, and arthropathy. An important gene associated with Winchester Syndrome is MMP14 (Matrix Metallopeptidase 14), and among its related pathways/superpathways are Degradation of the extracellular matrix and Development Endothelin-1/EDNRA signaling. Affiliated tissues include bone, skin and eye, and related phenotypes are coarse facial features and corneal opacity

OMIM : 56 Winchester syndrome presents with severe osteolysis in the hands and feet and generalized osteoporosis and bone thinning, similar to multicentric osteolysis, nodulosis, and arthropathy (MONA; 259600), but subcutaneous nodules are characteristically absent. Various additional features including coarse face, corneal opacities, gum hypertrophy, and EKG changes have been reported (summary by Zankl et al., 2007). (277950)

KEGG : 36 Winchester syndrome is a rare skeletal disorder originally described nearly 50 years ago in two sisters with a severe crippling osteolysis. Previously, Winchester syndrome and multicentric osteolysis, nodulosis, and arthropathy (MONA) [DS:H00472] were presumed to be allelic disorders arising from mutations in the MMP2 gene. But it has been demonstrated that mutations in MMP14 result in this disease.

UniProtKB/Swiss-Prot : 73 Winchester syndrome: A disease characterized by severe osteolysis in the hands and feet, generalized osteoporosis, bone thinning, and absence of subcutaneous nodules. Various additional features include coarse face, corneal opacities, gum hypertrophy, and EKG changes.

Wikipedia : 74 Winchester syndrome is a rare congenital connective tissue disease described in 1969, of which the main... more...

Related Diseases for Winchester Syndrome

Graphical network of the top 20 diseases related to Winchester Syndrome:



Diseases related to Winchester Syndrome

Symptoms & Phenotypes for Winchester Syndrome

Human phenotypes related to Winchester Syndrome:

31 (show all 7)
# Description HPO Frequency HPO Source Accession
1 coarse facial features 31 HP:0000280
2 corneal opacity 31 HP:0007957
3 gingival overgrowth 31 HP:0000212
4 arthropathy 31 HP:0003040
5 generalized osteoporosis 31 HP:0040160
6 osteolysis involving bones of the upper limbs 31 HP:0045039
7 osteolysis involving bones of the feet 31 HP:0009134

Clinical features from OMIM:

277950

Drugs & Therapeutics for Winchester Syndrome

Search Clinical Trials , NIH Clinical Center for Winchester Syndrome

Genetic Tests for Winchester Syndrome

Genetic tests related to Winchester Syndrome:

# Genetic test Affiliating Genes
1 Winchester Syndrome 29 MMP14

Anatomical Context for Winchester Syndrome

MalaCards organs/tissues related to Winchester Syndrome:

40
Bone, Skin, Eye, Heart, Testes

Publications for Winchester Syndrome

Articles related to Winchester Syndrome:

(show all 33)
# Title Authors PMID Year
1
Mutation of membrane type-1 metalloproteinase, MT1-MMP, causes the multicentric osteolysis and arthritis disease Winchester syndrome. 6 56 61
22922033 2012
2
A new acid mucopolysaccharidosis with skeletal deformities simulating rheumatoid arthritis. 56 6
4238825 1969
3
Torg syndrome is caused by inactivating mutations in MMP2 and is allelic to NAO and Winchester syndrome. 61 56
17059372 2007
4
A novel homozygous MMP2 mutation in a family with Winchester syndrome. 61 56
16542393 2006
5
Winchester syndrome caused by a homozygous mutation affecting the active site of matrix metalloproteinase 2. 56 61
15691365 2005
6
[Biochemical and ultrastructural study of two familial cases of Winchester syndrome]. 61 56
2625626 1989
7
Two cases of Winchester syndrome: with increased urinary oligosaccharide excretion. 56 61
3428299 1987
8
The Winchester syndrome: a nonlysosomal connective tissue disease. 56 61
4206841 1974
9
Winchester's syndrome. 56
2515281 1989
10
Peripheral corneal opacification and skeletal deformities. A newly recognized acid mucopolysaccharidosis simulating rheumatoid arthritis. 56
4246484 1970
11
Multicentric osteolytic syndromes represent a phenotypic spectrum defined by defective collagen remodeling. 61
31218820 2019
12
Functional analysis of a hypomorphic allele shows that MMP14 catalytic activity is the prime determinant of the Winchester syndrome phenotype. 61
29741626 2018
13
Langerhans Cell Histiocytosis Involving Both Jaws in an Adult. 61
28969735 2017
14
Identification of drug-target interaction from interactome network with 'guilt-by-association' principle and topology features. 61
26614126 2016
15
Treatment of Massive Labial and Gingival Hypertrophy in a Patient With Infantile Systemic Hyalinosis-A Case Report. 61
26207694 2015
16
A report of three patients with MMP2 associated hereditary osteolysis. 61
22876575 2012
17
The diagnosis and management of patients with idiopathic osteolysis. 61
21995273 2011
18
Winchester syndrome: the progression of radiological findings over a 23-year period. 61
20865259 2011
19
A novel homozygous MMP2 mutation in a patient with Torg-Winchester syndrome. 61
20720557 2010
20
Clinical and radiographic findings in two brothers affected with a novel mutation in matrix metalloproteinase 2 gene. 61
19653001 2010
21
Winchester syndrome: a case report. 61
19200197 2009
22
Torg-Winchester syndrome: lack of efficacy of pamidronate therapy. 61
17351352 2007
23
Progressive multilayered banded skin in Winchester syndrome. 61
14726867 2004
24
Winchester syndrome. 61
11794271 2001
25
[Winchester syndrome]. 61
11529039 2001
26
Winchester syndrome. A case report and literature review. 61
1437071 1992
27
Familial vanishing limbs: four generations of idiopathic multicentric osteolysis. 61
6617092 1983
28
The Winchester syndrome: (a case report). 61
730313 1978
29
Winchester syndrome: report of a case from Iran. 61
604368 1977
30
Idiopathic multicentric osteolysis. 61
175680 1976
31
Letter: The Winchester syndrome and mucopolysaccharide metabolism. 61
123957 1975
32
The skin in the Winchester syndrome. 61
1115514 1975
33
The Winchester syndrome: clinical, radiographic and pathologic studies. 61
4462644 1974

Variations for Winchester Syndrome

ClinVar genetic disease variations for Winchester Syndrome:

6 ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 MMP14 NM_004995.4(MMP14):c.50C>G (p.Thr17Arg)SNV Pathogenic 65463 rs587777039 14:23306076-23306076 14:22836867-22836867
2 MMP14 NM_004995.4(MMP14):c.850+2C>TSNV Uncertain significance 225413 rs757044765 14:23312629-23312629 14:22843420-22843420
3 MMP14 NM_004995.4(MMP14):c.440C>T (p.Ala147Val)SNV Uncertain significance 803006 14:23311678-23311678 14:22842469-22842469
4 MMP14 NM_004995.4(MMP14):c.542T>C (p.Phe181Ser)SNV Uncertain significance 803007 14:23311780-23311780 14:22842571-22842571

UniProtKB/Swiss-Prot genetic disease variations for Winchester Syndrome:

73
# Symbol AA change Variation ID SNP ID
1 MMP14 p.Thr17Arg VAR_070567 rs587777039

Expression for Winchester Syndrome

Search GEO for disease gene expression data for Winchester Syndrome.

Pathways for Winchester Syndrome

Pathways related to Winchester Syndrome according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.06 MMP2 MMP14
2
Show member pathways
11.96 MMP2 MMP14
3 11.54 MMP2 MMP14
4 11.35 MMP2 MMP14
5
Show member pathways
11.15 MMP2 MMP14
6 10.78 MMP2 MMP14
7 10.41 MMP2 MMP14

GO Terms for Winchester Syndrome

Cellular components related to Winchester Syndrome according to GeneCards Suite gene sharing:

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

Biological processes related to Winchester Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 proteolysis GO:0006508 9.43 MMP2 MMP14
2 angiogenesis GO:0001525 9.4 MMP2 MMP14
3 extracellular matrix organization GO:0030198 9.37 MMP2 MMP14
4 response to hypoxia GO:0001666 9.32 MMP2 MMP14
5 extracellular matrix disassembly GO:0022617 9.26 MMP2 MMP14
6 collagen catabolic process GO:0030574 9.16 MMP2 MMP14
7 endodermal cell differentiation GO:0035987 8.96 MMP2 MMP14
8 tissue remodeling GO:0048771 8.62 MMP2 MMP14

Molecular functions related to Winchester Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 peptidase activity GO:0008233 9.26 MMP2 MMP14
2 metallopeptidase activity GO:0008237 9.16 MMP2 MMP14
3 metalloendopeptidase activity GO:0004222 8.96 MMP2 MMP14
4 endopeptidase activity GO:0004175 8.62 MMP2 MMP14

Sources for Winchester Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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