MCID: PRX021
MIFTS: 49

Proximal Symphalangism malady

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

Aliases & Classifications for Proximal Symphalangism

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Sources:
11Disease Ontology, 46NIH Rare Diseases, 23GeneTests, 13DISEASES, 52Orphanet, 25GTR, 12diseasecard, 48Novoseek, 66UMLS, 29ICD10 via Orphanet, 38MESH via Orphanet, 67UMLS via Orphanet
See all MalaCards sources

Aliases & Descriptions for Proximal Symphalangism:

Name: Proximal Symphalangism 11 46 23 13 52
Symphalangism, Proximal 12 48 66
Symphalangism, Proximal, 1a 46 66
Symphalangism, Cushing Type 52 25
Cushing's Symphalangism 11 46
Hereditary Absence of the Proximal Interphalangeal Joints 23
 
Strasburger-Hawkins-Eldridge-Hargrave-Mckusick Syndrome 46
Hereditary Absence of Proximal Interphalangeal Joints 46
Strasburger-Hawkins-Eldridge Syndrome 46
Symphalangism, Proximal, 1b 46
Cushing Symphalangism 23
Vessel’s Syndrome 46

Characteristics:

Orphanet epidemiological data:

52
proximal symphalangism:
Inheritance: Autosomal dominant; Age of onset: Infancy,Neonatal

Classifications:



External Ids:

Disease Ontology11 DOID:0050788
Orphanet52 ORPHA3250
ICD10 via Orphanet29 Q70.9
MESH via Orphanet38 C536223
UMLS via Orphanet67 C1861385

Summaries for Proximal Symphalangism

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NIH Rare Diseases:46 Proximal symphalangism, which is also called cushing's symphalangism, is a rare genetic condition characterized by the fusion of the proximal joints in the hands and feet. these individuals usually have straight fingers and are unable to make a fist. other joints may also be affected, leading to stiff joints in the elbows, ankles and wrists. hearing loss due to the fusion of the auditory ossicles (bones in the middle ear) is also a characteristic feature. this condition is inherited in an autosomal dominant pattern and is caused by a mutation in the nog gene or gdf5 gene. last updated: 5/6/2011

MalaCards based summary: Proximal Symphalangism, also known as symphalangism, proximal, is related to symphalangism, proximal, 1b and robinow syndrome, autosomal recessive, and has symptoms including synostosis of carpal bones, tarsal synostosis and symphalangism affecting the phalanges of the hand. An important gene associated with Proximal Symphalangism is NOG (Noggin), and among its related pathways are Cardiac Progenitor Differentiation and Wnt signaling network. Affiliated tissues include bone, and related mouse phenotypes are digestive/alimentary and hearing/vestibular/ear.

Disease Ontology:11 An autosomal dominant disease that is characterized by ankylosis of the proximal interphalangeal joints, carpal and tarsal bone fusion, and conductive deafness.

Related Diseases for Proximal Symphalangism

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Diseases in the Proximal Symphalangism family:

Symphalangism, Proximal, 1a Symphalangism, Proximal, 1b

Diseases related to Proximal Symphalangism via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 30)
idRelated DiseaseScoreTop Affiliating Genes
1symphalangism, proximal, 1b34.4BMPR1B, GDF5
2robinow syndrome, autosomal recessive10.5NOG, ROR2
3multiple synostoses syndrome 210.4BMPR1B, GDF5
4brachydactyly, type a110.4BMPR1B, GDF5
5osteopetrosis and infantile neuroaxonal dystrophy10.3BMPR1B, FGF9
6systemic mastocytosis10.3BMP2, GDF5
7glutamate formiminotransferase deficiency10.2BMPR1B, GDF5, NOG
8pneumatosis cystoides intestinalis10.2BMP2, GDF5
9symphalangism, proximal, 1a10.2
10humeroradial synostosis10.1BMP2, BMP4
11premature ovarian failure10.1
12colorectal adenomatous polyposis, autosomal recessive, with pilomatricomas10.0BMP2, BMP4
13bone structure disease10.0BMP2, GDF5
14chromosomal disease10.0BMP2, GDF5
15cervical benign neoplasm10.0BMP2, BMP4
16acromesomelic dysplasia, demirhan type10.0BMP2, BMPR1B, GDF5
17brachydactyly, type b210.0NOG, ROR2, YIPF2
18charcot-marie-tooth disease type 510.0BMPR1B, GDF5, PAEP
19descending colon cancer10.0BMP2, BMP4, NOG
20vulvovaginitis9.9BMP2, BMP4, NOG
21tarsal-carpal coalition syndrome9.9
22brachydactyly, type c9.9
23brachydactyly9.9
24synostosis9.9
25fibrodysplasia ossificans progressiva9.9BMP4, NOG
26idiopathic corneal edema9.8BMP2, BMP4
27syphilitic myelopathy9.6BMP2, BMP4, FGF9, NOG
28congenital generalized lipodystrophy9.4BMP2, BMPR1B, GDF5, NOG, ROR2
29cerebral creatine deficiency syndrome7.2BMP4, BMPR1B, CSF1R, FGF9, GDF5, NOG
30short qt syndrome6.3BMP2, BMP4, BMPR1B, CSF1R, FGF9, GDF5

Graphical network of the top 20 diseases related to Proximal Symphalangism:



Diseases related to proximal symphalangism

Symptoms for Proximal Symphalangism

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Symptoms:

 52 (show all 15)
  • sensorineural hearing impairment
  • strabismus
  • brachydactyly syndrome
  • abnormality of the metacarpal bones
  • abnormality of the wrist
  • elbow dislocation
  • elbow ankylosis
  • clinodactyly of the 5th finger
  • synostosis of carpal bones
  • metacarpophalangeal synostosis
  • finger syndactyly
  • tarsal synostosis
  • finger clinodactyly
  • proximal symphalangism
  • camptodactyly of finger

HPO human phenotypes related to Proximal Symphalangism:

(show all 12)
id Description Frequency HPO Source Accession
1 synostosis of carpal bones hallmark (90%) HP:0005048
2 tarsal synostosis hallmark (90%) HP:0008368
3 symphalangism affecting the phalanges of the hand hallmark (90%) HP:0009773
4 camptodactyly of finger hallmark (90%) HP:0100490
5 sensorineural hearing impairment typical (50%) HP:0000407
6 brachydactyly syndrome typical (50%) HP:0001156
7 abnormality of the metacarpal bones typical (50%) HP:0001163
8 humeroradial synostosis typical (50%) HP:0003041
9 elbow dislocation typical (50%) HP:0003042
10 strabismus occasional (7.5%) HP:0000486
11 clinodactyly of the 5th finger occasional (7.5%) HP:0004209
12 finger syndactyly occasional (7.5%) HP:0006101

Drugs & Therapeutics for Proximal Symphalangism

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Interventional clinical trials:

idNameStatusNCT IDPhase
1Study of Skeletal Disorders and Short StatureCompletedNCT00001754
2Treatment of Proximal Interphalangeal Joint Injuries. Clinical Efficiency of Syndactyly Treatment and Digital CompressionRecruitingNCT02548260

Search NIH Clinical Center for Proximal Symphalangism

Genetic Tests for Proximal Symphalangism

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Genetic tests related to Proximal Symphalangism:

id Genetic test Affiliating Genes
1 Cushing's Symphalangism25
2 Proximal Symphalangism23 NOG

Anatomical Context for Proximal Symphalangism

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MalaCards organs/tissues related to Proximal Symphalangism:

34
Bone

Animal Models for Proximal Symphalangism or affiliated genes

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MGI Mouse Phenotypes related to Proximal Symphalangism:

39 (show all 14)
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053818.7BMP2, BMP4, FGF9, NOG, ROR2
2MP:00053778.6BMP2, BMP4, CSF1R, FGF9, NOG, ROR2
3MP:00053888.5BMP4, FGF9, NOG, ROR2, WNT2
4MP:00053798.3BMP4, BMPR1B, CSF1R, FGF9, NOG, ROR2
5MP:00053828.2BMP2, BMP4, BMPR1B, CSF1R, FGF9, NOG
6MP:00028738.2BMP2, BMP4, BMPR1B, CSF1R, FGF9, NOG
7MP:00053808.0BMP2, BMP4, BMPR1B, NOG, ROR2, WNT2
8MP:00053897.8BMP2, BMP4, BMPR1B, CSF1R, FGF9, GDF5
9MP:00053907.5BMP2, BMP4, BMPR1B, CSF1R, FGF9, GDF5
10MP:00053847.2BMP2, BMP4, BMPR1B, CSF1R, FGF9, NOG
11MP:00053717.2BMP2, BMP4, BMPR1B, CSF1R, FGF9, GDF5
12MP:00107686.8BMP2, BMP4, BMPR1B, CSF1R, FGF9, GDF5
13MP:00053786.5BMP2, BMP4, BMPR1B, CSF1R, FGF9, GDF5

Publications for Proximal Symphalangism

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Articles related to Proximal Symphalangism:

(show all 18)
idTitleAuthorsYear
1
A Novel Missense Mutation of NOG Interferes With the Dimerization of NOG and Causes Proximal Symphalangism Syndrome in a Chinese Family. (25888563)
2015
2
Identification of a novel NOG mutation in a Chinese family with proximal symphalangism. (24326127)
2014
3
A mutation in the heparin-binding site of noggin as a novel mechanism of proximal symphalangism and conductive hearing loss. (24735539)
2014
4
Proximal symphalangism and premature ovarian failure. (22088931)
2012
5
Foot anomalies and proximal symphalangism. (22294466)
2012
6
Proximal symphalangism, hyperopia, conductive hearing impairment, and the NOG gene: 2 new mutations. (21358557)
2011
7
Cushing proximal symphalangism and the NOG and GDF5 genes. (17994231)
2008
8
Novel point mutations in GDF5 associated with two distinct limb malformations in Chinese: brachydactyly type C and proximal symphalangism. (18283415)
2008
9
Premature ovarian failure in a female with proximal symphalangism and Noggin mutation. (15066478)
2004
10
Adult-onset idiopathic progressive acro-osteolysis with proximal symphalangism. (14753748)
2004
11
Proximal symphalangism with "coarse" facial appearance, mixed hearing loss, and chronic renal failure: new malformation syndrome? (11169566)
2001
12
Mutations of the NOG gene in individuals with proximal symphalangism and multiple synostosis syndrome. (11846737)
2001
13
Identical mutations in NOG can cause either tarsal/carpal coalition syndrome or proximal symphalangism. (11545688)
2001
14
Proximal symphalangism associated with conductive hearing loss. (14635304)
2000
15
Proximal symphalangism and congenital conductive hearing loss: otologic aspects. (10337976)
1999
16
Localization of the gene (SYM1) for proximal symphalangism to human chromosome 17q21-q22. (7557985)
1995
17
Stapes fixation a proximal symphalangism. (5440467)
1970
18
Proximal symphalangism of fingers associated with fusion of os naviculare and talus and occurrence of two accessory bones in the feet (os paranaviculare and os tibiale externum) in an European--Indonesian--Chinese family. (5633139)
1967

Variations for Proximal Symphalangism

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Clinvar genetic disease variations for Proximal Symphalangism:

5
id Gene Variation Type Significance SNP ID Assembly Location
1NOGNM_005450.4(NOG): c.665A> G (p.Tyr222Cys)single nucleotide variantPathogenicrs104894602GRCh37Chr 17, 54672249: 54672249
2NOGNM_005450.4(NOG): c.104C> G (p.Pro35Arg)single nucleotide variantPathogenicrs104894611GRCh37Chr 17, 54671688: 54671688
3NM_000557.4(GDF5): c.1313G> T (p.Arg438Leu)single nucleotide variantPathogenicrs74315388GRCh37Chr 20, 34021900: 34021900

Expression for genes affiliated with Proximal Symphalangism

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Search GEO for disease gene expression data for Proximal Symphalangism.

Pathways for genes affiliated with Proximal Symphalangism

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Pathways related to Proximal Symphalangism according to KEGG:

32
id Name KEGG Source Accession
1hsaH00484

Pathways related to Proximal Symphalangism according to GeneCards Suite gene sharing:

(show all 20)
idSuper pathwaysScoreTop Affiliating Genes
19.5BMP4, NOG, ROR2
29.3ROR2, WNT2
3
Show member pathways
9.3BMP2, BMPR1B, NOG
4
Show member pathways
9.2BMP2, BMP4, GDF5
59.2BMP2, BMP4, BMPR1B
69.0BMP2, BMP4, GDF5, NOG
79.0BMP4, NOG, WNT2
8
Show member pathways
8.6BMP2, BMP4, BMPR1B, GDF5, NOG
9
Show member pathways
8.6BMP2, BMP4, BMPR1B, GDF5, NOG
10
Show member pathways
8.5BMP2, BMP4, CSF1R, GDF5, ROR2
11
Show member pathways
8.4BMP2, BMP4, BMPR1B, CSF1R, GDF5
12
Show member pathways
8.4BMP2, BMP4, ROR2, WNT2
138.3BMP2, BMP4, BMPR1B, WNT2
14
Show member pathways
8.1BMP2, BMP4, CSF1R, FGF9, GDF5, ROR2
15
Show member pathways
8.1BMP2, BMP4, BMPR1B, CSF1R, GDF5, ROR2
16
Show member pathways
8.1BMP2, BMP4, BMPR1B, CSF1R, GDF5, ROR2
17
Show member pathways
8.1BMP2, BMP4, BMPR1B, NOG, WNT2
188.0BMP2, BMP4, BMPR1B, GDF5, WNT2
197.9BMP2, BMP4, CSF1R, FGF9, WNT2
20
Show member pathways
7.6BMP2, BMP4, CSF1R, GDF5, ROR2, WNT2

GO Terms for genes affiliated with Proximal Symphalangism

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Cellular components related to Proximal Symphalangism according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1extracellular spaceGO:00056157.8BMP2, BMP4, FGF9, GDF5, NOG, WNT2
2extracellular regionGO:00055767.0BMP2, BMP4, FGF9, GDF5, NOG, PAEP

Biological processes related to Proximal Symphalangism according to GeneCards Suite gene sharing:

(show top 50)    (show all 62)
idNameGO IDScoreTop Affiliating Genes
1transmembrane receptor protein serine/threonine kinase signaling pathwayGO:000717810.5BMPR1B, GDF5
2positive regulation of chondrocyte differentiationGO:003233210.5BMPR1B, GDF5
3lung morphogenesisGO:006042510.5BMP4, NOG
4embryonic skeletal joint morphogenesisGO:006027210.4BMP4, NOG
5cartilage condensationGO:000150210.4BMPR1B, ROR2
6mesenchymal cell differentiationGO:004876210.3BMP2, NOG
7negative regulation of chondrocyte differentiationGO:003233110.3BMP4, GDF5
8mesenchymal cell proliferation involved in ureteric bud developmentGO:007213810.2BMP2, BMP4
9BMP signaling pathway involved in heart inductionGO:000313010.2BMP2, BMP4
10telencephalon regionalizationGO:002197810.2BMP2, BMP4
11positive regulation of pri-miRNA transcription from RNA polymerase II promoterGO:190289510.2BMP2, BMP4
12positive regulation of ossificationGO:004577810.2BMP2, BMP4
13macrophage differentiationGO:003022510.2BMP4, CSF1R
14monocyte differentiationGO:003022410.2BMP4, CSF1R
15anatomical structure formation involved in morphogenesisGO:004864610.1BMP4, NOG
16embryonic digit morphogenesisGO:004273310.0BMP4, NOG, ROR2
17positive regulation of cardiac muscle cell proliferationGO:00600459.9FGF9, WNT2
18positive regulation of mesenchymal cell proliferationGO:00020539.9FGF9, WNT2
19peptidyl-tyrosine phosphorylationGO:00181089.8CSF1R, FGF9, ROR2
20positive regulation of bone mineralizationGO:00305019.8BMP2, BMP4, BMPR1B
21cardiac epithelial to mesenchymal transitionGO:00603179.8BMP2, WNT2
22positive regulation of pathway-restricted SMAD protein phosphorylationGO:00108629.8BMP2, BMP4, GDF5
23embryonic limb morphogenesisGO:00303269.7BMP4, FGF9, GDF5
24positive regulation of epithelial cell proliferationGO:00506799.7BMP4, FGF9, NOG
25positive regulation of cell differentiationGO:00455979.7BMP2, BMP4, BMPR1B
26positive regulation of cartilage developmentGO:00610369.7BMP2, BMP4, BMPR1B
27negative regulation of gene expressionGO:00106299.7BMP2, BMP4, NOG
28regulation of odontogenesis of dentin-containing toothGO:00424879.7BMP2, BMP4
29negative regulation of canonical Wnt signaling pathwayGO:00900909.6BMP2, NOG, ROR2
30cellular response to growth factor stimulusGO:00713639.6BMP2, BMP4, BMPR1B
31positive regulation of protein phosphorylationGO:00019349.6BMP2, BMP4, CSF1R
32embryonic skeletal system developmentGO:00487069.6BMP4, FGF9, NOG
33SMAD protein signal transductionGO:00603959.5BMP2, BMP4, GDF5, ROR2
34positive regulation of osteoblast differentiationGO:00456699.5BMP2, BMP4, BMPR1B
35positive regulation of neuron differentiationGO:00456669.5BMP2, BMP4, GDF5
36positive regulation of canonical Wnt signaling pathwayGO:00902639.4FGF9, ROR2, WNT2
37lung developmentGO:00303249.3BMP4, FGF9, WNT2
38positive regulation of endothelial cell proliferationGO:00019389.3BMP2, BMP4, WNT2
39osteoblast differentiationGO:00016499.3BMP2, BMP4, FGF9, NOG
40cellular response to BMP stimulusGO:00717739.3BMP2, BMP4, BMPR1B, NOG
41skeletal system developmentGO:00015019.2BMP2, BMP4, BMPR1B, NOG
42cell fate commitmentGO:00451659.1BMP2, BMP4, ROR2, WNT2
43chondrocyte differentiationGO:00020629.1BMP2, BMP4, BMPR1B, FGF9, GDF5
44positive regulation of ERK1 and ERK2 cascadeGO:00703749.0BMP2, BMP4, CSF1R
45BMP signaling pathwayGO:00305099.0BMP2, BMP4, BMPR1B, NOG, ROR2
46cell-cell signalingGO:00072678.9BMP2, FGF9, GDF5, WNT2
47positive regulation of cell migrationGO:00303358.9BMP2, BMP4, CSF1R, ROR2
48negative regulation of cell proliferationGO:00082858.8BMP2, BMP4, CSF1R, ROR2
49positive regulation of cell proliferationGO:00082848.1BMP4, CSF1R, FGF9, WNT2
50positive regulation of transcription from RNA polymerase II promoterGO:00459448.1BMP2, BMP4, BMPR1B, NOG, WNT2

Molecular functions related to Proximal Symphalangism according to GeneCards Suite gene sharing:

(show all 7)
idNameGO IDScoreTop Affiliating Genes
1BMP receptor bindingGO:007070010.0BMP2, BMP4
2cytokine bindingGO:00199559.7CSF1R, NOG
3transforming growth factor beta receptor bindingGO:00051609.7BMP2, BMP4, GDF5
4co-receptor bindingGO:00397069.5BMP2, BMP4
5frizzled bindingGO:00051099.5ROR2, WNT2
6growth factor activityGO:00080838.8BMP2, BMP4, FGF9, GDF5
7cytokine activityGO:00051258.5BMP2, BMP4, GDF5, WNT2

Sources for Proximal Symphalangism

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2CDC
6CNVD
10DGIdb
15ExPASy
16FDA
17FMA
25GTR
26HGMD
27HMDB
28ICD10
29ICD10 via Orphanet
30ICD9CM
31IUPHAR
32KEGG
35MedGen
37MeSH
38MESH via Orphanet
39MGI
42NCI
43NCIt
44NDF-RT
47NINDS
48Novoseek
50OMIM
51OMIM via Orphanet
55PubMed
56QIAGEN
61SNOMED-CT via Orphanet
65Tumor Gene Family of Databases
66UMLS
67UMLS via Orphanet