MCID: PRX021
MIFTS: 49

Proximal Symphalangism

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

Aliases & Classifications for Proximal Symphalangism

MalaCards integrated aliases for Proximal Symphalangism:

Name: Proximal Symphalangism 12 54 60 38 30 6 15
Symphalangism, Proximal 13 56 41 74
Cushing's Symphalangism 12 54
Strasburger-Hawkins-Eldridge-Hargrave-Mckusick Syndrome 54
Hereditary Absence of Proximal Interphalangeal Joints 54
Strasburger-Hawkins-Eldridge Syndrome 54
Symphalangism, Proximal, 1a 54
Symphalangism, Proximal, 1b 54
Symphalangism, Cushing Type 60

Characteristics:

Orphanet epidemiological data:

60
proximal symphalangism
Inheritance: Autosomal dominant; Age of onset: Infancy,Neonatal;

Classifications:



External Ids:

Disease Ontology 12 DOID:0050788
KEGG 38 H00851
MESH via Orphanet 46 C536223
ICD10 via Orphanet 35 Q70.9
UMLS via Orphanet 75 C1861385
Orphanet 60 ORPHA3250
UMLS 74 C1861385

Summaries for Proximal Symphalangism

NIH Rare Diseases : 54 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.

MalaCards based summary : Proximal Symphalangism, also known as symphalangism, proximal, is related to symphalangism, proximal, 1a and tarsal-carpal coalition syndrome. An important gene associated with Proximal Symphalangism is NOG (Noggin), and among its related pathways/superpathways are PEDF Induced Signaling and TGF-Beta Pathway. Affiliated tissues include bone, and related phenotypes are synostosis of carpal bones and camptodactyly of finger

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 33)
# Related Disease Score Top Affiliating Genes
1 symphalangism, proximal, 1a 34.5 NOG ROR2
2 tarsal-carpal coalition syndrome 29.9 NOG ROR2 YIPF2
3 brachydactyly 29.9 BMPR1B GDF5 NOG ROR2
4 brachydactyly, type c 29.9 BMPR1B GDF5 NOG ROR2
5 symphalangism, proximal, 1b 12.8
6 lenz-majewski hyperostotic dwarfism 11.3
7 multiple synostoses syndrome 1 11.2
8 mesomelia-synostoses syndrome 11.2
9 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.3
10 acromesomelic dysplasia, hunter-thompson type 10.2 BMPR1B GDF5
11 acromesomelic dysplasia 10.2 BMPR1B GDF5
12 chondrodysplasia, grebe type 10.2 BMPR1B GDF5
13 ankylosis 10.2 BMP4 NOG
14 premature ovarian failure 1 10.2
15 stapes ankylosis with broad thumbs and toes 10.2 BMP7 NOG
16 synostoses, tarsal, carpal, and digital 10.1 FGF9 GDF5 NOG
17 spondylolysis 10.1 BMP7 GDF5
18 spondylolisthesis 10.1 BMP7 GDF5
19 fibular hypoplasia and complex brachydactyly 10.1 BMPR1B GDF5 NOG
20 osteochondroma 10.1 BMPR1B FGF9
21 bone deterioration disease 10.1 BMP7 GDF5
22 synovial chondromatosis 10.1 BMP4 FGF9 NOG
23 fibrodysplasia ossificans progressiva 10.0 BMP4 NOG
24 brachydactyly, type a1 10.0 BMPR1B GDF5 ROR2
25 brachydactyly, type b1 10.0 BMP4 NOG ROR2
26 synostosis 10.0
27 otosclerosis 10.0 BMP4 NOG
28 osseous heteroplasia, progressive 10.0 BMP4 BMP7 NOG
29 bone structure disease 9.8 BMP7 GDF5
30 cleft palate with or without ankyloglossia, x-linked 9.8 BMP4 PAEP
31 brachydactyly, type b2 9.8 GDF5 NOG ROR2 YIPF2
32 brachydactyly, type a2 9.4 BMPR1B GDF5 NOG PAEP ROR2
33 multiple synostoses syndrome 8.2 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:

60 33 (show all 15)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 synostosis of carpal bones 60 33 hallmark (90%) Very frequent (99-80%) HP:0005048
2 camptodactyly of finger 60 33 hallmark (90%) Very frequent (99-80%) HP:0100490
3 tarsal synostosis 60 33 hallmark (90%) Very frequent (99-80%) HP:0008368
4 proximal symphalangism 60 33 hallmark (90%) Very frequent (99-80%) HP:0100264
5 sensorineural hearing impairment 60 33 frequent (33%) Frequent (79-30%) HP:0000407
6 brachydactyly 60 33 frequent (33%) Frequent (79-30%) HP:0001156
7 elbow dislocation 60 33 frequent (33%) Frequent (79-30%) HP:0003042
8 elbow ankylosis 60 33 frequent (33%) Frequent (79-30%) HP:0003070
9 metacarpophalangeal synostosis 60 33 frequent (33%) Frequent (79-30%) HP:0005880
10 finger syndactyly 60 33 occasional (7.5%) Occasional (29-5%) HP:0006101
11 strabismus 60 33 occasional (7.5%) Occasional (29-5%) HP:0000486
12 clinodactyly of the 5th finger 60 33 occasional (7.5%) Occasional (29-5%) HP:0004209
13 abnormality of the metacarpal bones 60 Frequent (79-30%)
14 finger clinodactyly 60 Frequent (79-30%)
15 abnormality of the wrist 60 Occasional (29-5%)

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

27
# 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:

47 (show all 13)
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 10.11 BMP4 BMP7 BMPR1B CSF1R FGF9 GDF5
2 craniofacial MP:0005382 10.07 BMP4 BMP7 BMPR1B CSF1R FGF9 NOG
3 embryo MP:0005380 10.04 BMP4 BMP7 BMPR1B FGF9 NOG ROR2
4 endocrine/exocrine gland MP:0005379 10.02 BMP4 BMP7 BMPR1B CSF1R FGF9 NOG
5 mortality/aging MP:0010768 10.02 BMP4 BMP7 BMPR1B CSF1R FGF9 GDF5
6 limbs/digits/tail MP:0005371 10.01 BMP4 BMP7 BMPR1B CSF1R FGF9 GDF5
7 digestive/alimentary MP:0005381 9.91 BMP4 BMP7 FGF9 NOG ROR2
8 hearing/vestibular/ear MP:0005377 9.91 BMP4 BMP7 CSF1R FGF9 NOG ROR2
9 reproductive system MP:0005389 9.86 BMP4 BMP7 BMPR1B CSF1R FGF9 GDF5
10 normal MP:0002873 9.8 BMP4 BMP7 BMPR1B CSF1R FGF9 NOG
11 respiratory system MP:0005388 9.63 BMP4 BMP7 FGF9 NOG ROR2 WNT2
12 skeleton MP:0005390 9.56 BMP4 BMP7 BMPR1B CSF1R FGF9 GDF5
13 vision/eye MP:0005391 9.1 BMP4 BMP7 BMPR1B FGF9 NOG ROR2

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 Proximal Symphalangism 30

Anatomical Context for Proximal Symphalangism

MalaCards organs/tissues related to Proximal Symphalangism:

42
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
Cushing proximal symphalangism and the NOG and GDF5 genes. ( 17994231 )
2008
10
Novel point mutations in GDF5 associated with two distinct limb malformations in Chinese: brachydactyly type C and proximal symphalangism. ( 18283415 )
2008
11
Premature ovarian failure in a female with proximal symphalangism and Noggin mutation. ( 15066478 )
2004
12
Adult-onset idiopathic progressive acro-osteolysis with proximal symphalangism. ( 14753748 )
2004
13
Mutations of the NOG gene in individuals with proximal symphalangism and multiple synostosis syndrome. ( 11846737 )
2001
14
Identical mutations in NOG can cause either tarsal/carpal coalition syndrome or proximal symphalangism. ( 11545688 )
2001
15
Proximal symphalangism with "coarse" facial appearance, mixed hearing loss, and chronic renal failure: new malformation syndrome? ( 11169566 )
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 18)
# 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.665A> G (p.Tyr222Cys) single nucleotide variant Pathogenic rs104894602 GRCh38 Chromosome 17, 56594888: 56594888
3 NOG NM_005450.4(NOG): c.664T> G (p.Tyr222Asp) single nucleotide variant Pathogenic rs121908948 GRCh37 Chromosome 17, 54672248: 54672248
4 NOG NM_005450.4(NOG): c.664T> G (p.Tyr222Asp) single nucleotide variant Pathogenic rs121908948 GRCh38 Chromosome 17, 56594887: 56594887
5 NOG NM_005450.4(NOG): c.668C> T (p.Pro223Leu) single nucleotide variant Pathogenic rs104894608 GRCh37 Chromosome 17, 54672252: 54672252
6 NOG NM_005450.4(NOG): c.668C> T (p.Pro223Leu) single nucleotide variant Pathogenic rs104894608 GRCh38 Chromosome 17, 56594891: 56594891
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.565G> T (p.Gly189Cys) single nucleotide variant Pathogenic rs104894609 GRCh38 Chromosome 17, 56594788: 56594788
9 NOG NM_005450.4(NOG): c.104C> G (p.Pro35Arg) single nucleotide variant Pathogenic rs104894611 GRCh37 Chromosome 17, 54671688: 54671688
10 NOG NM_005450.4(NOG): c.104C> G (p.Pro35Arg) single nucleotide variant Pathogenic rs104894611 GRCh38 Chromosome 17, 56594327: 56594327
11 NOG NM_005450.4(NOG): c.551G> A (p.Cys184Tyr) single nucleotide variant Pathogenic rs104894612 GRCh37 Chromosome 17, 54672135: 54672135
12 NOG NM_005450.4(NOG): c.551G> A (p.Cys184Tyr) single nucleotide variant Pathogenic rs104894612 GRCh38 Chromosome 17, 56594774: 56594774
13 NOG NM_005450.4(NOG): c.386T> A (p.Leu129Ter) single nucleotide variant Pathogenic rs104894613 GRCh37 Chromosome 17, 54671970: 54671970
14 NOG NM_005450.4(NOG): c.386T> A (p.Leu129Ter) single nucleotide variant Pathogenic rs104894613 GRCh38 Chromosome 17, 56594609: 56594609
15 NOG NM_005450.4(NOG): c.103C> T (p.Pro35Ser) single nucleotide variant Pathogenic rs28937580 GRCh37 Chromosome 17, 54671687: 54671687
16 NOG NM_005450.4(NOG): c.103C> T (p.Pro35Ser) single nucleotide variant Pathogenic rs28937580 GRCh38 Chromosome 17, 56594326: 56594326
17 NOG NM_005450.4(NOG): c.599T> C (p.Leu200Pro) single nucleotide variant Likely pathogenic GRCh37 Chromosome 17, 54672183: 54672183
18 NOG NM_005450.4(NOG): c.599T> C (p.Leu200Pro) single nucleotide variant Likely pathogenic GRCh38 Chromosome 17, 56594822: 56594822

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 21)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.42 BMP4 BMP7 BMPR1B CSF1R GDF5 ROR2
2
Show member pathways
13.26 BMP4 BMP7 CSF1R FGF9 GDF5 ROR2
3
Show member pathways
13.13 BMP4 BMP7 BMPR1B CSF1R GDF5 ROR2
4
Show member pathways
13.07 BMP4 BMP7 CSF1R GDF5 ROR2
5
Show member pathways
13.05 BMP4 BMP7 BMPR1B CSF1R GDF5
6
Show member pathways
12.98 BMP4 BMP7 CSF1R GDF5 ROR2 WNT2
7 12.58 BMP4 CSF1R FGF9 WNT2
8
Show member pathways
12.1 BMP4 BMP7 BMPR1B NOG WNT2
9
Show member pathways
12.06 BMP4 BMP7 CSF1R GDF5 ROR2
10 11.86 BMP4 BMPR1B WNT2
11 11.82 BMP4 NOG WNT2
12 11.74 BMP4 BMP7 BMPR1B GDF5 WNT2
13
Show member pathways
11.53 BMP4 BMP7 GDF5
14
Show member pathways
11.51 BMP7 BMPR1B NOG
15 11.31 BMP4 BMP7 BMPR1B GDF5 NOG
16 11.3 BMP4 NOG ROR2
17 11.02 ROR2 WNT2
18 10.97 BMP4 BMP7
19 10.84 BMP4 BMP7 BMPR1B
20 10.73 BMP4 BMP7 CSF1R GDF5 ROR2
21 10.7 BMP4 CSF1R GDF5 NOG WNT2

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 9.43 BMP4 BMP7 FGF9 GDF5 NOG WNT2
2 receptor complex GO:0043235 9.33 BMPR1B CSF1R ROR2
3 extracellular region GO:0005576 9.17 BMP4 BMP7 FGF9 GDF5 NOG PAEP

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

(show top 50) (show all 76)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of gene expression GO:0010628 9.99 BMP4 BMP7 FGF9 NOG
2 regulation of signaling receptor activity GO:0010469 9.97 BMP4 BMP7 FGF9 GDF5 WNT2
3 cell differentiation GO:0030154 9.95 BMP4 BMP7 BMPR1B FGF9 NOG ROR2
4 regulation of apoptotic process GO:0042981 9.93 BMP4 BMP7 GDF5
5 positive regulation of cell migration GO:0030335 9.92 BMP4 CSF1R ROR2
6 multicellular organism development GO:0007275 9.92 BMP4 BMP7 CSF1R FGF9 NOG PAEP
7 cell-cell signaling GO:0007267 9.91 FGF9 GDF5 WNT2
8 axon guidance GO:0007411 9.91 BMP7 CSF1R NOG
9 peptidyl-tyrosine phosphorylation GO:0018108 9.89 CSF1R FGF9 ROR2
10 osteoblast differentiation GO:0001649 9.86 BMP4 FGF9 NOG
11 lung development GO:0030324 9.86 BMP4 FGF9 WNT2
12 positive regulation of neuron differentiation GO:0045666 9.85 BMP4 BMP7 GDF5
13 pattern specification process GO:0007389 9.82 BMP7 BMPR1B NOG
14 cell fate commitment GO:0045165 9.82 BMP4 ROR2 WNT2
15 positive regulation of epithelial cell proliferation GO:0050679 9.81 BMP4 FGF9 NOG
16 cell development GO:0048468 9.81 BMP4 BMP7 GDF5
17 positive regulation of osteoblast differentiation GO:0045669 9.8 BMP4 BMP7 BMPR1B
18 regulation of MAPK cascade GO:0043408 9.8 BMP4 BMP7 GDF5
19 embryonic digit morphogenesis GO:0042733 9.79 BMP4 NOG ROR2
20 positive regulation of pathway-restricted SMAD protein phosphorylation GO:0010862 9.77 BMP4 BMP7 GDF5
21 positive regulation of cell differentiation GO:0045597 9.77 BMP4 BMP7 BMPR1B
22 skeletal system development GO:0001501 9.77 BMP4 BMP7 BMPR1B NOG ROR2
23 negative regulation of cell cycle GO:0045786 9.75 BMP4 BMP7
24 positive regulation of epithelial to mesenchymal transition GO:0010718 9.75 BMP4 BMP7
25 dorsal/ventral pattern formation GO:0009953 9.75 BMPR1B NOG
26 positive regulation of ERK1 and ERK2 cascade GO:0070374 9.75 BMP4 CSF1R
27 negative regulation of MAP kinase activity GO:0043407 9.74 BMP4 BMP7
28 epithelial to mesenchymal transition GO:0001837 9.74 BMP7 NOG
29 positive regulation of cardiac muscle cell proliferation GO:0060045 9.74 FGF9 WNT2
30 metanephros development GO:0001656 9.74 BMP4 BMP7
31 positive regulation of BMP signaling pathway GO:0030513 9.74 BMP4 GDF5
32 ureteric bud development GO:0001657 9.74 BMP4 BMP7 NOG
33 protein localization to nucleus GO:0034504 9.73 BMP4 BMP7
34 endoderm development GO:0007492 9.73 BMP4 NOG
35 pituitary gland development GO:0021983 9.73 BMP4 NOG
36 embryonic skeletal system development GO:0048706 9.73 BMP4 FGF9 NOG
37 SMAD protein signal transduction GO:0060395 9.73 BMP4 BMP7 GDF5 ROR2
38 branching morphogenesis of an epithelial tube GO:0048754 9.72 BMP4 BMP7
39 positive regulation of protein phosphorylation GO:0001934 9.72 BMP4 CSF1R
40 positive regulation of mesenchymal cell proliferation GO:0002053 9.72 FGF9 WNT2
41 camera-type eye morphogenesis GO:0048593 9.72 BMP4 BMP7
42 eye development GO:0001654 9.72 BMP7 BMPR1B FGF9
43 lung morphogenesis GO:0060425 9.71 BMP4 NOG
44 positive regulation of chondrocyte differentiation GO:0032332 9.71 BMPR1B GDF5
45 cartilage condensation GO:0001502 9.71 BMPR1B ROR2
46 transmembrane receptor protein serine/threonine kinase signaling pathway GO:0007178 9.71 BMPR1B GDF5
47 negative regulation of chondrocyte differentiation GO:0032331 9.71 BMP4 GDF5
48 positive regulation of bone mineralization GO:0030501 9.71 BMP4 BMP7 BMPR1B
49 embryonic limb morphogenesis GO:0030326 9.71 BMP4 BMP7 FGF9 GDF5
50 macrophage differentiation GO:0030225 9.7 BMP4 CSF1R

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

# Name GO ID Score Top Affiliating Genes
1 protein tyrosine kinase activity GO:0004713 9.54 CSF1R FGF9 ROR2
2 heparin binding GO:0008201 9.5 BMP4 BMP7 FGF9
3 cytokine activity GO:0005125 9.46 BMP4 BMP7 GDF5 WNT2
4 cytokine binding GO:0019955 9.43 CSF1R NOG
5 frizzled binding GO:0005109 9.4 ROR2 WNT2
6 BMP receptor binding GO:0070700 9.26 BMP4 BMP7
7 transforming growth factor beta receptor binding GO:0005160 9.13 BMP4 BMP7 GDF5
8 growth factor activity GO:0008083 8.92 BMP4 BMP7 FGF9 GDF5

Sources for Proximal Symphalangism

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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