MCID: PRX021
MIFTS: 51

Proximal Symphalangism

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

Aliases & Classifications for Proximal Symphalangism

MalaCards integrated aliases for Proximal Symphalangism:

Name: Proximal Symphalangism 12 49 55 36 14
Cushing's Symphalangism 12 49 28
Symphalangism, Proximal 13 51 69
Strasburger-Hawkins-Eldridge-Hargrave-Mckusick Syndrome 49
Hereditary Absence of Proximal Interphalangeal Joints 49
Strasburger-Hawkins-Eldridge Syndrome 49
Symphalangism, Proximal, 1a 49
Symphalangism, Proximal, 1b 49
Symphalangism, Cushing Type 55
Vessel’s Syndrome 49

Characteristics:

Orphanet epidemiological data:

55
proximal symphalangism
Inheritance: Autosomal dominant; Age of onset: Infancy,Neonatal;

Classifications:



External Ids:

Disease Ontology 12 DOID:0050788
Orphanet 55 ORPHA3250
MESH via Orphanet 42 C536223
UMLS via Orphanet 70 C1861385
ICD10 via Orphanet 33 Q70.9
KEGG 36 H00484
UMLS 69 C1861385

Summaries for Proximal Symphalangism

NIH Rare Diseases : 49 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 cushing's symphalangism, is related to multiple synostoses syndrome 1 and brachydactyly, type c, and has symptoms including sensorineural hearing impairment, strabismus and brachydactyly. An important gene associated with Proximal Symphalangism is NOG (Noggin), and among its related pathways/superpathways are TGF-beta signaling pathway and MAPK signaling pathway. Affiliated tissues include bone, and related phenotypes are Increased cell viability after pRB stimulation and growth/size/body region

Disease Ontology : 12 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

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 35)
# Related Disease Score Top Affiliating Genes
1 multiple synostoses syndrome 1 32.1 GDF5 NOG
2 brachydactyly, type c 30.3 BMPR1B GDF5
3 tarsal-carpal coalition syndrome 29.8 NOG ROR2 YIPF2
4 brachydactyly 29.2 BMP2 BMPR1B GDF5 NOG ROR2
5 symphalangism, proximal, 1b 12.6
6 lenz-majewski hyperostotic dwarfism 11.0
7 symphalangism with multiple anomalies of hands and feet 11.0
8 mesomelia-synostoses syndrome 11.0
9 brachydactyly, type b1 10.3 NOG ROR2
10 acromesomelic dysplasia, hunter-thompson type 10.3 BMPR1B GDF5
11 chondrodysplasia, grebe type 10.3 BMPR1B GDF5
12 spondylolysis 10.2 BMP7 GDF5
13 fibular hypoplasia and complex brachydactyly 10.2 BMPR1B GDF5 NOG
14 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.2
15 brachydactyly, type a1 10.2 BMPR1B GDF5
16 pseudoarthrosis 10.1 BMP2 BMP7
17 premature ovarian failure 1 10.0
18 ossification of the posterior longitudinal ligament of spine 10.0 BMP2 BMP4
19 brachydactyly, type a2 10.0 BMP2 BMPR1B GDF5
20 osteochondroma 9.9 BMP2 BMPR1B FGF9
21 ankylosis 9.9 BMP2 BMP4 NOG
22 spondylolisthesis 9.9 BMP2 BMP7 GDF5
23 otosclerosis 9.9 BMP2 BMP4 NOG
24 bone deterioration disease 9.9 BMP2 BMP7 GDF5
25 fibrochondrogenesis 9.9 BMP2 BMP4
26 bone structure disease 9.9 BMP2 BMP7 GDF5
27 symphalangism, proximal, 1a 9.9
28 synostosis 9.9
29 craniosynostosis 9.9 BMP2 FGF9 NOG
30 brain glioma 9.8 BMP2 BMP4
31 synovial chondromatosis 9.8 BMP2 BMP4 FGF9 NOG
32 acromesomelic dysplasia 9.7 BMPR1B GDF5 PAEP
33 bullous keratopathy 9.7 BMP2 BMP4
34 osseous heteroplasia, progressive 9.7 BMP2 BMP4 BMP7 NOG
35 multiple synostoses syndrome 7.9 BMP4 BMPR1B CSF1R FGF9 GDF5 NOG

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



Diseases related to Proximal Symphalangism

Symptoms & Phenotypes for Proximal Symphalangism

Human phenotypes related to Proximal Symphalangism:

55 31 (show all 15)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 sensorineural hearing impairment 55 31 frequent (33%) Frequent (79-30%) HP:0000407
2 strabismus 55 31 occasional (7.5%) Occasional (29-5%) HP:0000486
3 brachydactyly 55 31 frequent (33%) Frequent (79-30%) HP:0001156
4 elbow dislocation 55 31 frequent (33%) Frequent (79-30%) HP:0003042
5 elbow ankylosis 55 31 frequent (33%) Frequent (79-30%) HP:0003070
6 clinodactyly of the 5th finger 55 31 occasional (7.5%) Occasional (29-5%) HP:0004209
7 synostosis of carpal bones 55 31 hallmark (90%) Very frequent (99-80%) HP:0005048
8 metacarpophalangeal synostosis 55 31 frequent (33%) Frequent (79-30%) HP:0005880
9 finger syndactyly 55 31 occasional (7.5%) Occasional (29-5%) HP:0006101
10 tarsal synostosis 55 31 hallmark (90%) Very frequent (99-80%) HP:0008368
11 proximal symphalangism 55 31 hallmark (90%) Very frequent (99-80%) HP:0100264
12 camptodactyly of finger 55 31 hallmark (90%) Very frequent (99-80%) HP:0100490
13 abnormality of the metacarpal bones 55 Frequent (79-30%)
14 abnormality of the wrist 55 Occasional (29-5%)
15 finger clinodactyly 55 Frequent (79-30%)

GenomeRNAi Phenotypes related to Proximal Symphalangism according to GeneCards Suite gene sharing:

25
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased cell viability after pRB stimulation GR00230-A-1 8.8 BMPR1B CSF1R ROR2

MGI Mouse Phenotypes related to Proximal Symphalangism:

43 (show all 15)
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 10.16 NOG FGF9 ROR2 GDF5 CSF1R BMP7
2 cellular MP:0005384 10.14 CSF1R NOG FGF9 ROR2 BMP2 BMPR1B
3 craniofacial MP:0005382 10.13 FGF9 ROR2 NOG BMP7 BMP2 BMP4
4 embryo MP:0005380 10.1 NOG FGF9 ROR2 WNT2 BMP7 BMP2
5 cardiovascular system MP:0005385 10.09 NOG FGF9 ROR2 BMP4 BMP2 BMP7
6 mortality/aging MP:0010768 10.07 NOG FGF9 ROR2 GDF5 CSF1R BMP7
7 limbs/digits/tail MP:0005371 10.06 FGF9 ROR2 GDF5 NOG BMP7 BMP2
8 endocrine/exocrine gland MP:0005379 10.02 CSF1R NOG FGF9 ROR2 BMP7 BMPR1B
9 digestive/alimentary MP:0005381 9.99 NOG FGF9 ROR2 BMP7 BMP2 BMP4
10 hearing/vestibular/ear MP:0005377 9.98 FGF9 ROR2 NOG CSF1R BMP7 BMP2
11 reproductive system MP:0005389 9.91 FGF9 ROR2 GDF5 NOG CSF1R BMP7
12 normal MP:0002873 9.87 CSF1R NOG FGF9 BMP7 BMP2 BMPR1B
13 respiratory system MP:0005388 9.63 NOG FGF9 ROR2 BMP7 BMP4 WNT2
14 skeleton MP:0005390 9.61 FGF9 ROR2 GDF5 CSF1R NOG BMP7
15 vision/eye MP:0005391 9.1 NOG FGF9 ROR2 BMP7 BMPR1B BMP4

Drugs & Therapeutics for Proximal Symphalangism

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Study of Skeletal Disorders and Short Stature Completed NCT00001754

Search NIH Clinical Center for Proximal Symphalangism

Genetic Tests for Proximal Symphalangism

Genetic tests related to Proximal Symphalangism:

# Genetic test Affiliating Genes
1 Cushing's Symphalangism 28 NOG

Anatomical Context for Proximal Symphalangism

MalaCards organs/tissues related to Proximal Symphalangism:

38
Bone

Publications for Proximal Symphalangism

Articles related to Proximal Symphalangism:

(show all 20)
# Title Authors Year
1
Knock-in human GDF5 proregion L373R mutation as a mouse model for proximal symphalangism. ( 29371961 )
2017
2
Recurrent missense mutation of GDF5 (p.R438L) causes proximal symphalangism in a British family. ( 28032038 )
2016
3
A Novel Missense Mutation of NOG Interferes With the Dimerization of NOG and Causes Proximal Symphalangism Syndrome in a Chinese Family. ( 25888563 )
2015
4
A mutation in the heparin-binding site of noggin as a novel mechanism of proximal symphalangism and conductive hearing loss. ( 24735539 )
2014
5
Identification of a novel NOG mutation in a Chinese family with proximal symphalangism. ( 24326127 )
2014
6
Foot anomalies and proximal symphalangism. ( 22294466 )
2012
7
Proximal symphalangism and premature ovarian failure. ( 22088931 )
2012
8
Proximal symphalangism, hyperopia, conductive hearing impairment, and the NOG gene: 2 new mutations. ( 21358557 )
2011
9
Novel point mutations in GDF5 associated with two distinct limb malformations in Chinese: brachydactyly type C and proximal symphalangism. ( 18283415 )
2008
10
Cushing proximal symphalangism and the NOG and GDF5 genes. ( 17994231 )
2008
11
Adult-onset idiopathic progressive acro-osteolysis with proximal symphalangism. ( 14753748 )
2004
12
Premature ovarian failure in a female with proximal symphalangism and Noggin mutation. ( 15066478 )
2004
13
Mutations of the NOG gene in individuals with proximal symphalangism and multiple synostosis syndrome. ( 11846737 )
2001
14
Proximal symphalangism with "coarse" facial appearance, mixed hearing loss, and chronic renal failure: new malformation syndrome? ( 11169566 )
2001
15
Identical mutations in NOG can cause either tarsal/carpal coalition syndrome or proximal symphalangism. ( 11545688 )
2001
16
Proximal symphalangism associated with conductive hearing loss. ( 14635304 )
2000
17
Proximal symphalangism and congenital conductive hearing loss: otologic aspects. ( 10337976 )
1999
18
Localization of the gene (SYM1) for proximal symphalangism to human chromosome 17q21-q22. ( 7557985 )
1995
19
Stapes fixation a proximal symphalangism. ( 5440467 )
1970
20
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

ClinVar genetic disease variations for Proximal Symphalangism:

6 (show all 11)
# Gene Variation Type Significance SNP ID Assembly Location
1 GDF5 NM_000557.4(GDF5): c.1118T> G (p.Leu373Arg) single nucleotide variant Pathogenic rs121909349 GRCh37 Chromosome 20, 34022095: 34022095
2 GDF5 NM_000557.4(GDF5): c.1313G> T (p.Arg438Leu) single nucleotide variant Pathogenic rs74315388 GRCh37 Chromosome 20, 34021900: 34021900
3 GDF5 NM_000557.4(GDF5): c.1471G> A (p.Glu491Lys) single nucleotide variant Pathogenic rs74315389 GRCh37 Chromosome 20, 34021742: 34021742
4 NOG NM_005450.4(NOG): c.665A> G (p.Tyr222Cys) single nucleotide variant Pathogenic rs104894602 GRCh37 Chromosome 17, 54672249: 54672249
5 NOG NM_005450.4(NOG): c.664T> G (p.Tyr222Asp) single nucleotide variant Pathogenic rs121908948 GRCh37 Chromosome 17, 54672248: 54672248
6 NOG NM_005450.4(NOG): c.668C> T (p.Pro223Leu) single nucleotide variant Pathogenic rs104894608 GRCh37 Chromosome 17, 54672252: 54672252
7 NOG NM_005450.4(NOG): c.565G> T (p.Gly189Cys) single nucleotide variant Pathogenic rs104894609 GRCh37 Chromosome 17, 54672149: 54672149
8 NOG NM_005450.4(NOG): c.104C> G (p.Pro35Arg) single nucleotide variant Pathogenic rs104894611 GRCh37 Chromosome 17, 54671688: 54671688
9 NOG NM_005450.4(NOG): c.551G> A (p.Cys184Tyr) single nucleotide variant Pathogenic rs104894612 GRCh37 Chromosome 17, 54672135: 54672135
10 NOG NM_005450.4(NOG): c.386T> A (p.Leu129Ter) single nucleotide variant Pathogenic rs104894613 GRCh37 Chromosome 17, 54671970: 54671970
11 NOG NM_005450.4(NOG): c.103C> T (p.Pro35Ser) single nucleotide variant Pathogenic rs28937580 GRCh37 Chromosome 17, 54671687: 54671687

Expression for Proximal Symphalangism

Search GEO for disease gene expression data for Proximal Symphalangism.

Pathways for Proximal Symphalangism

Pathways related to Proximal Symphalangism according to KEGG:

36
# Name Kegg Source Accession
1 TGF-beta signaling pathway hsa04350
2 MAPK signaling pathway hsa04010
3 Regulation of actin cytoskeleton hsa04810

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

(show all 31)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.64 BMP2 BMP4 BMP7 BMPR1B CSF1R GDF5
2
Show member pathways
13.54 BMP2 BMP4 BMP7 CSF1R FGF9 GDF5
3
Show member pathways
13.47 BMP2 BMP4 BMP7 BMPR1B CSF1R GDF5
4
Show member pathways
13.38 BMP2 BMP4 BMP7 CSF1R GDF5 ROR2
5
Show member pathways
13.34 BMP2 BMP4 BMP7 CSF1R FGF9 GDF5
6
Show member pathways
13.2 BMP2 BMP4 BMP7 BMPR1B CSF1R GDF5
7
Show member pathways
13.14 BMP2 BMP4 BMP7 CSF1R GDF5 ROR2
8
Show member pathways
13.11 BMP2 BMP4 BMP7 BMPR1B CSF1R GDF5
9
Show member pathways
13.09 BMP2 BMP4 BMP7 CSF1R GDF5 ROR2
10
Show member pathways
12.88 BMP2 BMP4 BMP7 CSF1R GDF5
11 12.66 BMP2 BMP4 CSF1R FGF9 WNT2
12
Show member pathways
12.59 BMP2 BMP4 BMP7 GDF5
13
Show member pathways
12.53 BMP2 BMP4 BMP7 GDF5
14
Show member pathways
12.34 BMP2 BMP4 BMP7 BMPR1B
15
Show member pathways
12.29 BMP2 BMP4 BMP7 BMPR1B NOG WNT2
16
Show member pathways
12.21 BMP2 BMP4 ROR2 WNT2
17 11.94 BMP4 BMPR1B WNT2
18 11.9 BMP2 BMP4 BMP7
19 11.9 BMP4 NOG WNT2
20 11.82 BMP2 BMP4 BMP7 BMPR1B GDF5 WNT2
21 11.7 BMP2 BMP4 BMP7 GDF5 NOG
22
Show member pathways
11.6 BMP2 BMP4 BMP7 GDF5
23
Show member pathways
11.56 BMP2 BMP7 BMPR1B NOG
24 11.42 BMP4 NOG ROR2
25 11.09 ROR2 WNT2
26 11.05 BMP2 BMP4 BMP7
27 11.05 BMP2 BMP4 BMP7
28 11.03 BMP4 CSF1R GDF5 NOG WNT2
29 11.02 BMP2 BMP4 BMP7 BMPR1B GDF5 NOG
30 10.9 BMP2 BMP4 BMP7 BMPR1B
31 10.84 BMP2 BMP4 BMP7 CSF1R GDF5 ROR2

GO Terms for Proximal Symphalangism

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

# Name GO ID Score Top Affiliating Genes
1 extracellular space GO:0005615 9.5 BMP2 BMP4 BMP7 FGF9 GDF5 NOG
2 extracellular region GO:0005576 9.23 BMP2 BMP4 BMP7 FGF9 GDF5 NOG

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

(show top 50) (show all 90)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of cell migration GO:0030335 9.97 BMP2 BMP4 CSF1R ROR2
2 negative regulation of gene expression GO:0010629 9.94 BMP2 BMP4 NOG
3 positive regulation of ERK1 and ERK2 cascade GO:0070374 9.94 BMP2 BMP4 CSF1R
4 axon guidance GO:0007411 9.94 BMP7 CSF1R NOG
5 peptidyl-tyrosine phosphorylation GO:0018108 9.93 CSF1R FGF9 ROR2
6 negative regulation of canonical Wnt signaling pathway GO:0090090 9.92 BMP2 NOG ROR2
7 positive regulation of protein phosphorylation GO:0001934 9.92 BMP2 BMP4 CSF1R
8 positive regulation of canonical Wnt signaling pathway GO:0090263 9.91 FGF9 ROR2 WNT2
9 lung development GO:0030324 9.9 BMP4 FGF9 WNT2
10 osteoblast differentiation GO:0001649 9.9 BMP2 BMP4 FGF9 NOG
11 ossification GO:0001503 9.89 BMP2 BMP4 BMP7
12 positive regulation of neuron differentiation GO:0045666 9.88 BMP2 BMP4 BMP7 GDF5
13 positive regulation of endothelial cell proliferation GO:0001938 9.87 BMP2 BMP4 WNT2
14 positive regulation of epithelial cell proliferation GO:0050679 9.86 BMP4 FGF9 NOG
15 embryonic digit morphogenesis GO:0042733 9.86 BMP4 NOG ROR2
16 odontogenesis of dentin-containing tooth GO:0042475 9.86 BMP2 BMP4 BMP7
17 cellular response to growth factor stimulus GO:0071363 9.85 BMP2 BMP4 BMPR1B
18 cell development GO:0048468 9.85 BMP2 BMP7 GDF5
19 positive regulation of osteoblast differentiation GO:0045669 9.84 BMP2 BMP4 BMP7 BMPR1B
20 positive regulation of epithelial to mesenchymal transition GO:0010718 9.83 BMP2 BMP4 BMP7
21 negative regulation of cell cycle GO:0045786 9.83 BMP2 BMP4 BMP7
22 cell fate commitment GO:0045165 9.83 BMP2 BMP4 ROR2 WNT2
23 ureteric bud development GO:0001657 9.82 BMP4 BMP7 NOG
24 epithelial to mesenchymal transition GO:0001837 9.81 BMP2 BMP7 NOG
25 embryonic skeletal system development GO:0048706 9.8 BMP4 FGF9 NOG
26 mesoderm formation GO:0001707 9.8 BMP4 BMP7 NOG
27 embryonic limb morphogenesis GO:0030326 9.8 BMP4 BMP7 FGF9 GDF5
28 skeletal system development GO:0001501 9.8 BMP2 BMP4 BMP7 BMPR1B NOG ROR2
29 eye development GO:0001654 9.79 BMP7 BMPR1B FGF9
30 positive regulation of pathway-restricted SMAD protein phosphorylation GO:0010862 9.78 BMP2 BMP4 BMP7 GDF5
31 positive regulation of cardiac muscle cell proliferation GO:0060045 9.77 FGF9 WNT2
32 bone mineralization GO:0030282 9.77 BMP2 ROR2
33 anatomical structure formation involved in morphogenesis GO:0048646 9.77 BMP4 BMP7 NOG
34 SMAD protein signal transduction GO:0060395 9.77 BMP2 BMP4 BMP7 GDF5 ROR2
35 positive regulation of BMP signaling pathway GO:0030513 9.76 BMP4 GDF5
36 metanephros development GO:0001656 9.76 BMP4 BMP7
37 protein localization to nucleus GO:0034504 9.76 BMP4 BMP7
38 endoderm development GO:0007492 9.76 BMP4 NOG
39 pituitary gland development GO:0021983 9.76 BMP4 NOG
40 cardiac muscle cell differentiation GO:0055007 9.76 BMP2 BMP4
41 positive regulation of cell differentiation GO:0045597 9.76 BMP2 BMP4 BMP7 BMPR1B
42 branching morphogenesis of an epithelial tube GO:0048754 9.75 BMP4 BMP7
43 positive regulation of mesenchymal cell proliferation GO:0002053 9.75 FGF9 WNT2
44 telencephalon development GO:0021537 9.75 BMP2 BMP4
45 positive regulation of pri-miRNA transcription by RNA polymerase II GO:1902895 9.75 BMP2 BMP4
46 camera-type eye morphogenesis GO:0048593 9.74 BMP4 BMP7
47 lung morphogenesis GO:0060425 9.74 BMP4 NOG
48 negative regulation of phosphorylation GO:0042326 9.74 BMP4 BMP7
49 cartilage condensation GO:0001502 9.74 BMPR1B ROR2
50 positive regulation of chondrocyte differentiation GO:0032332 9.74 BMPR1B GDF5

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

# Name GO ID Score Top Affiliating Genes
1 cytokine activity GO:0005125 9.65 BMP2 BMP4 BMP7 GDF5 WNT2
2 protein tyrosine kinase activity GO:0004713 9.61 CSF1R FGF9 ROR2
3 heparin binding GO:0008201 9.58 BMP4 BMP7 FGF9
4 growth factor activity GO:0008083 9.55 BMP2 BMP4 BMP7 FGF9 GDF5
5 frizzled binding GO:0005109 9.46 ROR2 WNT2
6 cytokine binding GO:0019955 9.37 CSF1R NOG
7 co-receptor binding GO:0039706 9.32 BMP2 BMP4
8 BMP receptor binding GO:0070700 9.13 BMP2 BMP4 BMP7
9 transforming growth factor beta receptor binding GO:0005160 8.92 BMP2 BMP4 BMP7 GDF5

Sources for Proximal Symphalangism

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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