MCID: PRX021
MIFTS: 50

Proximal Symphalangism malady

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

Aliases & Classifications for Proximal Symphalangism

Aliases & Descriptions for Proximal Symphalangism:

Name: Proximal Symphalangism 12 50 24 56 14
Symphalangism, Proximal 13 52 69
Symphalangism, Proximal, 1a 50 69
Symphalangism, Cushing Type 56 29
Cushing's Symphalangism 12 50
Hereditary Absence of the Proximal Interphalangeal Joints 24
Strasburger-Hawkins-Eldridge-Hargrave-Mckusick Syndrome 50
Hereditary Absence of Proximal Interphalangeal Joints 50
Strasburger-Hawkins-Eldridge Syndrome 50
Symphalangism, Proximal, 1b 50
Cushing Symphalangism 24
Vessel’s Syndrome 50

Characteristics:

Orphanet epidemiological data:

56
proximal symphalangism
Inheritance: Autosomal dominant; Age of onset: Infancy,Neonatal;

Classifications:



External Ids:

Disease Ontology 12 DOID:0050788
Orphanet 56 ORPHA3250
UMLS via Orphanet 70 C1861385
MESH via Orphanet 43 C536223
ICD10 via Orphanet 34 Q70.9

Summaries for Proximal Symphalangism

NIH Rare Diseases : 50 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 tarsal-carpal coalition syndrome, and has symptoms including finger syndactyly, sensorineural hearing impairment and strabismus. An important gene associated with Proximal Symphalangism is NOG (Noggin), and among its related pathways/superpathways are GPCR Pathway and PEDF Induced Signaling. 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 31)
id Related Disease Score Top Affiliating Genes
1 symphalangism, proximal, 1b 34.0 BMPR1B GDF5
2 tarsal-carpal coalition syndrome 27.4 BMP2 BMP4 BMP7 BMPR1B CSF1R FGF9
3 symphalangism, proximal, 1a 11.1
4 loeys-dietz syndrome 1 10.2 NOG ROR2
5 stapes ankylosis with broad thumb and toes 10.2 GDF5 NOG
6 multiple synostoses syndrome 2 10.2 BMPR1B GDF5
7 charcot-marie-tooth disease type 7 10.1 BMPR1B GDF5
8 glutamate formiminotransferase deficiency 10.1 BMPR1B GDF5 NOG
9 pulmonary fibrosis 10.1 BMP2 BMP7
10 nocardiosis 10.1 BMP7 GDF5
11 juvenile onset parkinson disease 19a 10.1 BMP2 BMP4
12 cerebrotendinous xanthomatosis 10.1 BMPR1B GDF5
13 bronchus cancer 10.1 BMP2 GDF5
14 immunodeficiency, common variable, 12 10.1 BMP2 BMPR1B GDF5
15 splenic flexure cancer 10.0 BMP2 BMP4 NOG
16 pharyngitis 10.0 BMP2 BMP4 NOG
17 systemic scleroderma 10.0 BMP2 BMP7 GDF5
18 bone resorption disease 10.0 BMP2 BMP7 GDF5
19 ovarian epithelial cancer 10.0 BMP2 BMPR1B FGF9
20 brachydactyly, type b2 10.0 NOG ROR2 YIPF2
21 physical disorder 10.0 BMP2 BMP7 GDF5
22 premature ovarian failure 10.0
23 t cell immunodeficiency primary 9.9 BMP2 BMP4 FGF9 NOG
24 salt and pepper syndrome 9.9 BMP2 BMP4
25 acth-independent macronodular adrenal hyperplasia 9.9 BMP2 BMP4 BMP7 NOG
26 muscular dystrophy-dystroglycanopathy 9.9 BMP2 BMPR1B GDF5 NOG ROR2
27 brachydactyly, type c 9.8
28 brachydactyly 9.8
29 synostosis 9.8
30 androgenic alopecia 8.9 BMP4 BMPR1B CSF1R FGF9 GDF5 NOG
31 multiple synostoses syndrome 8.5 BMP2 BMP4 BMP7 BMPR1B CSF1R FGF9

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:

56 32 (show all 15)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 finger syndactyly 56 32 Occasional (29-5%) HP:0006101
2 sensorineural hearing impairment 56 32 Frequent (79-30%) HP:0000407
3 strabismus 56 32 Occasional (29-5%) HP:0000486
4 clinodactyly of the 5th finger 56 32 Occasional (29-5%) HP:0004209
5 brachydactyly syndrome 56 32 Frequent (79-30%) HP:0001156
6 elbow dislocation 56 32 Frequent (79-30%) HP:0003042
7 synostosis of carpal bones 56 32 Very frequent (99-80%) HP:0005048
8 camptodactyly of finger 56 32 Very frequent (99-80%) HP:0100490
9 tarsal synostosis 56 32 Very frequent (99-80%) HP:0008368
10 elbow ankylosis 56 32 Frequent (79-30%) HP:0003070
11 metacarpophalangeal synostosis 56 32 Frequent (79-30%) HP:0005880
12 proximal symphalangism 56 32 Very frequent (99-80%) HP:0100264
13 abnormality of the metacarpal bones 56 Frequent (79-30%)
14 finger clinodactyly 56 Frequent (79-30%)
15 abnormality of the wrist 56 Occasional (29-5%)

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

26
id 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:

44 (show all 15)
id Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 10.16 BMP2 BMP4 BMP7 BMPR1B CSF1R FGF9
2 cellular MP:0005384 10.14 BMP2 BMP4 BMPR1B CSF1R FGF9 NOG
3 craniofacial MP:0005382 10.13 BMP2 BMP4 BMP7 BMPR1B CSF1R FGF9
4 cardiovascular system MP:0005385 10.09 FGF9 NOG ROR2 WNT2 BMP7 BMP2
5 mortality/aging MP:0010768 10.07 CSF1R FGF9 GDF5 NOG ROR2 WNT2
6 limbs/digits/tail MP:0005371 10.06 GDF5 NOG ROR2 BMP2 BMP4 BMP7
7 embryo MP:0005380 10.04 BMP2 BMP4 BMP7 BMPR1B NOG ROR2
8 endocrine/exocrine gland MP:0005379 10.02 BMP4 BMP7 BMPR1B CSF1R FGF9 NOG
9 digestive/alimentary MP:0005381 9.99 BMP2 BMP4 BMP7 FGF9 NOG ROR2
10 hearing/vestibular/ear MP:0005377 9.98 BMP2 BMP4 BMP7 CSF1R FGF9 NOG
11 reproductive system MP:0005389 9.91 BMP2 BMP4 BMP7 BMPR1B CSF1R FGF9
12 normal MP:0002873 9.87 BMP2 BMP4 BMP7 BMPR1B CSF1R FGF9
13 respiratory system MP:0005388 9.63 BMP4 BMP7 FGF9 NOG ROR2 WNT2
14 skeleton MP:0005390 9.61 BMP7 BMPR1B CSF1R FGF9 GDF5 NOG
15 vision/eye MP:0005391 9.1 BMP4 BMP7 BMPR1B FGF9 NOG ROR2

Drugs & Therapeutics for Proximal Symphalangism

Interventional clinical trials:


id Name Status NCT ID Phase
1 Study of Skeletal Disorders and Short Stature Completed NCT00001754
2 Treatment of Proximal Interphalangeal Joint Injuries. Clinical Efficiency of Syndactyly Treatment and Digital Compression Recruiting NCT02548260

Search NIH Clinical Center for Proximal Symphalangism

Genetic Tests for Proximal Symphalangism

Genetic tests related to Proximal Symphalangism:

id Genetic test Affiliating Genes
1 Cushing's Symphalangism 29
2 Proximal Symphalangism 24 NOG

Anatomical Context for Proximal Symphalangism

MalaCards organs/tissues related to Proximal Symphalangism:

39
Bone

Publications for Proximal Symphalangism

Articles related to Proximal Symphalangism:

(show all 19)
id Title Authors Year
1
Recurrent missense mutation of GDF5 (p.R438L) causes proximal symphalangism in a British family. ( 28032038 )
2016
2
A Novel Missense Mutation of NOG Interferes With the Dimerization of NOG and Causes Proximal Symphalangism Syndrome in a Chinese Family. ( 25888563 )
2015
3
A mutation in the heparin-binding site of noggin as a novel mechanism of proximal symphalangism and conductive hearing loss. ( 24735539 )
2014
4
Identification of a novel NOG mutation in a Chinese family with proximal symphalangism. ( 24326127 )
2014
5
Foot anomalies and proximal symphalangism. ( 22294466 )
2012
6
Proximal symphalangism and premature ovarian failure. ( 22088931 )
2012
7
Proximal symphalangism, hyperopia, conductive hearing impairment, and the NOG gene: 2 new mutations. ( 21358557 )
2011
8
Cushing proximal symphalangism and the NOG and GDF5 genes. ( 17994231 )
2008
9
Novel point mutations in GDF5 associated with two distinct limb malformations in Chinese: brachydactyly type C and proximal symphalangism. ( 18283415 )
2008
10
Premature ovarian failure in a female with proximal symphalangism and Noggin mutation. ( 15066478 )
2004
11
Adult-onset idiopathic progressive acro-osteolysis with proximal symphalangism. ( 14753748 )
2004
12
Identical mutations in NOG can cause either tarsal/carpal coalition syndrome or proximal symphalangism. ( 11545688 )
2001
13
Proximal symphalangism with "coarse" facial appearance, mixed hearing loss, and chronic renal failure: new malformation syndrome? ( 11169566 )
2001
14
Mutations of the NOG gene in individuals with proximal symphalangism and multiple synostosis syndrome. ( 11846737 )
2001
15
Proximal symphalangism associated with conductive hearing loss. ( 14635304 )
2000
16
Proximal symphalangism and congenital conductive hearing loss: otologic aspects. ( 10337976 )
1999
17
Localization of the gene (SYM1) for proximal symphalangism to human chromosome 17q21-q22. ( 7557985 )
1995
18
Stapes fixation a proximal symphalangism. ( 5440467 )
1970
19
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)
id Gene Variation Type Significance SNP ID Assembly Location
1 NOG NM_005450.4(NOG): c.665A> G (p.Tyr222Cys) single nucleotide variant Pathogenic rs104894602 GRCh37 Chromosome 17, 54672249: 54672249
2 NOG NM_005450.4(NOG): c.664T> G (p.Tyr222Asp) single nucleotide variant Pathogenic rs121908948 GRCh37 Chromosome 17, 54672248: 54672248
3 NOG NM_005450.4(NOG): c.668C> T (p.Pro223Leu) single nucleotide variant Pathogenic rs104894608 GRCh37 Chromosome 17, 54672252: 54672252
4 NOG NM_005450.4(NOG): c.565G> T (p.Gly189Cys) single nucleotide variant Pathogenic rs104894609 GRCh37 Chromosome 17, 54672149: 54672149
5 NOG NM_005450.4(NOG): c.104C> G (p.Pro35Arg) single nucleotide variant Pathogenic rs104894611 GRCh37 Chromosome 17, 54671688: 54671688
6 NOG NM_005450.4(NOG): c.551G> A (p.Cys184Tyr) single nucleotide variant Pathogenic rs104894612 GRCh37 Chromosome 17, 54672135: 54672135
7 NOG NM_005450.4(NOG): c.386T> A (p.Leu129Ter) single nucleotide variant Pathogenic rs104894613 GRCh37 Chromosome 17, 54671970: 54671970
8 NOG NM_005450.4(NOG): c.103C> T (p.Pro35Ser) single nucleotide variant Pathogenic rs28937580 GRCh37 Chromosome 17, 54671687: 54671687
9 GDF5 NM_000557.4(GDF5): c.1313G> T (p.Arg438Leu) single nucleotide variant Pathogenic rs74315388 GRCh37 Chromosome 20, 34021900: 34021900
10 GDF5 NM_000557.4(GDF5): c.1471G> A (p.Glu491Lys) single nucleotide variant Pathogenic rs74315389 GRCh37 Chromosome 20, 34021742: 34021742
11 GDF5 NM_000557.4(GDF5): c.1118T> G (p.Leu373Arg) single nucleotide variant Pathogenic rs121909349 GRCh37 Chromosome 20, 34022095: 34022095

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 GeneCards Suite gene sharing:

(show all 31)
id Super pathways Score Top Affiliating Genes
1
Show member pathways
13.54 BMP2 BMP4 BMP7 CSF1R FGF9 GDF5
2
Show member pathways
13.47 BMP2 BMP4 BMP7 BMPR1B CSF1R GDF5
3
Show member pathways
13.38 BMP2 BMP4 BMP7 CSF1R GDF5 ROR2
4
Show member pathways
13.33 BMP2 BMP4 BMP7 CSF1R FGF9 GDF5
5
Show member pathways
13.2 BMP2 BMP4 BMP7 BMPR1B CSF1R GDF5
6
Show member pathways
13.14 BMP2 BMP4 BMP7 CSF1R GDF5 ROR2
7
Show member pathways
13.11 BMP2 BMP4 BMP7 BMPR1B CSF1R GDF5
8
Show member pathways
13.07 BMP2 BMP4 BMP7 CSF1R GDF5 ROR2
9
Show member pathways
12.88 BMP2 BMP4 BMP7 CSF1R GDF5
10
Show member pathways
12.71 BMP2 BMP4 BMP7 WNT2
11
Show member pathways
12.58 BMP2 BMP4 BMP7 GDF5
12
Show member pathways
12.53 BMP2 BMP4 BMP7 GDF5
13 12.49 BMP2 BMP4 CSF1R FGF9 WNT2
14
Show member pathways
12.32 BMP2 BMP4 BMP7 BMPR1B
15
Show member pathways
12.29 BMP2 BMP4 BMP7 BMPR1B NOG WNT2
16
Show member pathways
12.19 BMP2 BMP4 ROR2 WNT2
17 11.94 BMP4 BMPR1B WNT2
18 11.91 BMP4 NOG WNT2
19 11.82 BMP2 BMP4 BMP7 BMPR1B GDF5 WNT2
20 11.7 BMP2 BMP4 BMP7 GDF5 NOG
21
Show member pathways
11.6 BMP2 BMP4 BMP7 GDF5
22 11.58 BMP2 BMP4 BMP7 GDF5
23
Show member pathways
11.56 BMP2 BMP7 BMPR1B NOG
24 11.54 BMP2 BMP4 BMP7
25 11.42 BMP4 NOG ROR2
26 11.08 ROR2 WNT2
27 11.05 BMP2 BMP4 BMP7
28 11.03 BMP2 BMP4 BMP7
29 11.03 BMP4 CSF1R GDF5 NOG WNT2
30 11.02 BMP2 BMP4 BMP7 BMPR1B GDF5 NOG
31 10.9 BMP2 BMP4 BMP7 BMPR1B

GO Terms for Proximal Symphalangism

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

id Name GO ID Score Top Affiliating Genes
1 extracellular region GO:0005576 9.56 BMP2 BMP4 BMP7 FGF9 GDF5 NOG
2 extracellular space GO:0005615 9.17 BMP2 BMP4 BMP7 FGF9 GDF5 NOG

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

(show top 50) (show all 88)
id Name GO ID Score Top Affiliating Genes
1 positive regulation of cell migration GO:0030335 9.95 BMP2 BMP4 CSF1R ROR2
2 axon guidance GO:0007411 9.94 BMP7 CSF1R NOG
3 positive regulation of ERK1 and ERK2 cascade GO:0070374 9.93 BMP2 BMP4 CSF1R
4 negative regulation of gene expression GO:0010629 9.92 BMP2 BMP4 NOG
5 peptidyl-tyrosine phosphorylation GO:0018108 9.92 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 9.9 FGF9 ROR2 WNT2
9 lung development GO:0030324 9.89 BMP4 FGF9 WNT2
10 ossification GO:0001503 9.89 BMP2 BMP4 BMP7
11 osteoblast differentiation GO:0001649 9.89 BMP2 BMP4 FGF9 NOG
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 9.85 BMP4 NOG ROR2
16 odontogenesis of dentin-containing tooth GO:0042475 9.85 BMP2 BMP4 BMP7
17 cellular response to growth factor stimulus GO:0071363 9.85 BMP2 BMP4 BMPR1B
18 cell development GO:0048468 9.84 BMP2 BMP7 GDF5
19 cell fate commitment GO:0045165 9.84 BMP2 BMP4 ROR2 WNT2
20 positive regulation of osteoblast differentiation GO:0045669 9.83 BMP2 BMP4 BMP7 BMPR1B
21 ureteric bud development GO:0001657 9.82 BMP4 BMP7 NOG
22 negative regulation of cell cycle GO:0045786 9.81 BMP2 BMP4 BMP7
23 epithelial to mesenchymal transition GO:0001837 9.8 BMP2 BMP7 NOG
24 embryonic limb morphogenesis GO:0030326 9.8 BMP4 BMP7 FGF9 GDF5
25 skeletal system development GO:0001501 9.8 BMP2 BMP4 BMP7 BMPR1B NOG ROR2
26 embryonic skeletal system development GO:0048706 9.79 BMP4 FGF9 NOG
27 mesoderm formation GO:0001707 9.79 BMP4 BMP7 NOG
28 eye development GO:0001654 9.78 BMP7 BMPR1B FGF9
29 positive regulation of cell differentiation GO:0045597 9.78 BMP2 BMP4 BMP7 BMPR1B
30 negative regulation of MAP kinase activity GO:0043407 9.77 BMP4 BMP7
31 SMAD protein signal transduction GO:0060395 9.77 BMP2 BMP4 BMP7 GDF5 ROR2
32 bone mineralization GO:0030282 9.76 BMP2 ROR2
33 positive regulation of BMP signaling pathway GO:0030513 9.76 BMP4 GDF5
34 protein localization to nucleus GO:0034504 9.76 BMP4 BMP7
35 metanephros development GO:0001656 9.76 BMP4 BMP7
36 pituitary gland development GO:0021983 9.76 BMP4 NOG
37 endoderm development GO:0007492 9.76 BMP4 NOG
38 cardiac muscle cell differentiation GO:0055007 9.76 BMP2 BMP4
39 anatomical structure formation involved in morphogenesis GO:0048646 9.76 BMP4 BMP7 NOG
40 positive regulation of pathway-restricted SMAD protein phosphorylation GO:0010862 9.76 BMP2 BMP4 BMP7 GDF5
41 branching morphogenesis of an epithelial tube GO:0048754 9.75 BMP4 BMP7
42 telencephalon development GO:0021537 9.75 BMP2 BMP4
43 positive regulation of mesenchymal cell proliferation GO:0002053 9.75 FGF9 WNT2
44 positive regulation of cardiac muscle cell proliferation GO:0060045 9.74 FGF9 WNT2
45 cartilage condensation GO:0001502 9.74 BMPR1B ROR2
46 positive regulation of pri-miRNA transcription from RNA polymerase II promoter GO:1902895 9.74 BMP2 BMP4
47 lung morphogenesis GO:0060425 9.74 BMP4 NOG
48 negative regulation of phosphorylation GO:0042326 9.74 BMP4 BMP7
49 camera-type eye morphogenesis GO:0048593 9.74 BMP4 BMP7
50 positive regulation of cartilage development GO:0061036 9.74 BMP2 BMP4 BMPR1B

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

id 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
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 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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