TCC
MCID: TRS002
MIFTS: 42

Tarsal-Carpal Coalition Syndrome (TCC)

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

Aliases & Classifications for Tarsal-Carpal Coalition Syndrome

MalaCards integrated aliases for Tarsal-Carpal Coalition Syndrome:

Name: Tarsal-Carpal Coalition Syndrome 57 12 43 58 72 36 29 13 6 15 70
Tcc 57 20 43 72 17
Nog-Related-Symphalangism Spectrum Disorder 43
Syndrome, Tarsal-Carpal Coalition 39
Tarsal Carpal Coalition Syndrome 20

Characteristics:

Orphanet epidemiological data:

58
tarsal-carpal coalition syndrome
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Neonatal;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal dominant

Miscellaneous:
allelic to proximal symphalangism , multiple synostoses syndrome , and stapes ankylosis syndrome without symphalangism


HPO:

31
tarsal-carpal coalition syndrome:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Rare bone diseases
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 12 DOID:0050789
OMIM® 57 186570
KEGG 36 H00778
MESH via Orphanet 45 C536943
ICD10 via Orphanet 33 Q74.8
UMLS via Orphanet 71 C1861305
Orphanet 58 ORPHA1412
UMLS 70 C1861305

Summaries for Tarsal-Carpal Coalition Syndrome

MedlinePlus Genetics : 43 Tarsal-carpal coalition syndrome is a rare, inherited bone disorder that affects primarily the hands and feet. Several individual bones make up each wrist (carpal bones) and ankle (tarsal bones). In tarsal-carpal coalition syndrome, the carpal bones fuse together, as do the tarsal bones, which causes stiffness and immobility of the hands and feet. Symptoms of the condition can become apparent in infancy, and they worsen with age. The severity of the symptoms can vary, even among members of the same family.In this condition, fusion at the joints between the bones that make up each finger and toe (symphalangism) can also occur. Consequently, the fingers and toes become stiff and difficult to bend. Stiffness of the pinky fingers and toes (fifth digits) is usually noticeable first. The joints at the base of the pinky fingers and toes fuse first, and slowly, the other joints along the length of these digits may also be affected. Progressively, the bones in the fourth, third, and second digits (the ring finger, middle finger, and forefinger, and the corresponding toes) become fused. The thumb and big toe are usually not involved. Affected individuals have increasing trouble forming a fist, and walking often becomes painful and difficult. Occasionally, there is also fusion of bones in the upper and lower arm at the elbow joint (humeroradial fusion). Less common features of tarsal-carpal coalition syndrome include short stature or the development of hearing loss.

MalaCards based summary : Tarsal-Carpal Coalition Syndrome, also known as tcc, is related to ankylosis and multiple synostoses syndrome. An important gene associated with Tarsal-Carpal Coalition Syndrome is NOG (Noggin), and among its related pathways/superpathways are TGF-beta signaling pathway and Mesodermal Commitment Pathway. Related phenotypes are short stature and abnormality of the ankles

Disease Ontology : 12 A dysostosis that is characterized by fusion of the carpals, tarsals, and phalanges, short first metacarpals causing brachydactyly; and humeroradial fusion.

GARD : 20 Tarsal carpal coalition syndrome (TCC) is a genetic condition characterized by fusion of the bones in the wrist (carpals), ankles (tarsals), and the fingers and toes (phalanges). Other bone abnormalities in the hands and feet may be present. Symptoms of TCC may include: stiffness and progressive immobility of the hands and feet and short stature. TCC is caused by mutations in the NOG gene, and it is inherited in an autosomal dominant manner. Although there is no specific treatment or cure for TCC, there may be ways to manage the symptoms. A team of doctors or specialists is often needed to figure out the treatment options for each person.

KEGG : 36 Tarsal-carpal coalition syndrome is a condition characterized by fusion of the carpals, tarsals, and phalanges in addition to shortened first metacarpals, brachydactyly, and humeroradial fusion. The fusion of the proximal interphalangeal joints starts at the fifth digit and proceeds to other digits. Humeroradial fusion can also be seen. It is inherited in an autosomal dominant pattern.

UniProtKB/Swiss-Prot : 72 Tarsal-carpal coalition syndrome: Autosomal dominant disorder characterized by fusion of the carpals, tarsals and phalanges, short first metacarpals causing brachydactyly, and humeroradial fusion. TCC is allelic to SYM1, and different mutations in NOG can result in either TCC or SYM1 in different families.

More information from OMIM: 186570

Related Diseases for Tarsal-Carpal Coalition Syndrome

Diseases related to Tarsal-Carpal Coalition Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 81)
# Related Disease Score Top Affiliating Genes
1 ankylosis 30.5 NOG GDF5 ACVR1
2 multiple synostoses syndrome 30.2 YIPF2 NOG GDF5
3 synostosis 30.0 NOG GDF5
4 brachydactyly, type b2 29.6 YIPF2 NOG GDF5 CHRD ACVR1
5 proximal symphalangism 29.3 YIPF2 NOG GDF5 CHRD ACVR1
6 spastic paraplegia 11, autosomal recessive 11.3
7 bladder small cell carcinoma 11.2
8 spastic paraplegia 11 11.0
9 transitional cell carcinoma 10.7
10 stapes ankylosis with broad thumbs and toes 10.4
11 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.4
12 bladder cancer 10.4
13 strabismus 10.2
14 multiple synostoses syndrome 1 10.2
15 alacrima, achalasia, and mental retardation syndrome 10.2
16 proximal symphalangism 2 10.2
17 suppression amblyopia 10.2
18 amblyopia 10.2
19 mechanical strabismus 10.2
20 symphalangism, proximal, 1a 10.2
21 tarsal coalition 10.2
22 brachydactyly 10.2
23 sugarman brachydactyly 10.1 NOG GDF5
24 brachydactyly, type b1 10.1 NOG GDF5
25 du pan syndrome 10.1 NOG GDF5
26 paraplegia 10.0
27 in situ carcinoma 10.0
28 microphthalmia, isolated 4 10.0 GDF5 ACVR1
29 osseous heteroplasia, progressive 10.0 NOG ACVR1
30 ataxia and polyneuropathy, adult-onset 10.0
31 alpha-1-antitrypsin deficiency 10.0
32 toxic shock syndrome 10.0
33 hereditary spastic paraplegia 10.0
34 glomerulonephritis 10.0
35 bladder urothelial carcinoma 10.0
36 pulmonary emphysema 10.0
37 fibrodysplasia ossificans progressiva 9.9 NOG ACVR1
38 brachydactyly, type a1 9.9 YIPF2 NOG GDF5
39 bone development disease 9.9 NOG GDF5
40 brachydactyly, type a1, c 9.9 NOG GDF5 ACVR1
41 brachydactyly, type a1, b 9.9 NOG GDF5 ACVR1
42 brachydactyly, type a2 9.9 NOG GDF5 ACVR1
43 renal cell carcinoma, nonpapillary 9.8
44 schistosoma mansoni infection, susceptibility/ 9.8
45 friedreich ataxia 9.8
46 mast syndrome 9.8
47 lymphoma, non-hodgkin, familial 9.8
48 leukemia, chronic myeloid 9.8
49 beta-thalassemia 9.8
50 membranous nephropathy 9.8

Graphical network of the top 20 diseases related to Tarsal-Carpal Coalition Syndrome:



Diseases related to Tarsal-Carpal Coalition Syndrome

Symptoms & Phenotypes for Tarsal-Carpal Coalition Syndrome

Human phenotypes related to Tarsal-Carpal Coalition Syndrome:

58 31 (show all 14)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 short stature 58 31 hallmark (90%) Very frequent (99-80%) HP:0004322
2 abnormality of the ankles 58 31 hallmark (90%) Very frequent (99-80%) HP:0003028
3 tarsal synostosis 58 31 frequent (33%) Very frequent (99-80%) HP:0008368
4 short 1st metacarpal 31 frequent (33%) HP:0010034
5 radial deviation of finger 31 frequent (33%) HP:0009466
6 carpal synostosis 31 frequent (33%) HP:0009702
7 proximal symphalangism of hands 31 frequent (33%) HP:0006152
8 cubitus valgus 31 occasional (7.5%) HP:0002967
9 humeroradial synostosis 31 occasional (7.5%) HP:0003041
10 distal symphalangism of hands 31 occasional (7.5%) HP:0001204
11 brachydactyly 31 HP:0001156
12 short finger 31 HP:0009381
13 clinodactyly 31 HP:0030084
14 progressive fusion 2nd-5th pip joints 31 HP:0006147

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Skeletal Limbs:
cubitus valgus
humeroradial fusion

Growth Height:
normal height

Head And Neck Ears:
normal hearing

Skeletal Hands:
brachydactyly
clinodactyly
progressive fusion 2nd-5th pip joints
carpal fusion
symphalangism
more
Skeletal Feet:
tarsal fusion

Clinical features from OMIM®:

186570 (Updated 05-Apr-2021)

MGI Mouse Phenotypes related to Tarsal-Carpal Coalition Syndrome:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 craniofacial MP:0005382 9.8 ACVR1 CHRD CRIM1 NKX3-2 NOG
2 embryo MP:0005380 9.8 ACVR1 CHRD CRIM1 GDF5 NKX3-2 NOG
3 digestive/alimentary MP:0005381 9.77 ACVR1 CHRD CRIM1 NKX3-2 NOG
4 hearing/vestibular/ear MP:0005377 9.56 ACVR1 CHRD NKX3-2 NOG
5 limbs/digits/tail MP:0005371 9.55 ACVR1 CRIM1 GDF5 NKX3-2 NOG
6 muscle MP:0005369 9.35 ACVR1 CHRD CRIM1 NKX3-2 NOG
7 skeleton MP:0005390 9.1 ACVR1 CHRD CRIM1 GDF5 NKX3-2 NOG

Drugs & Therapeutics for Tarsal-Carpal Coalition Syndrome

Search Clinical Trials , NIH Clinical Center for Tarsal-Carpal Coalition Syndrome

Genetic Tests for Tarsal-Carpal Coalition Syndrome

Genetic tests related to Tarsal-Carpal Coalition Syndrome:

# Genetic test Affiliating Genes
1 Tarsal-Carpal Coalition Syndrome 29 NOG

Anatomical Context for Tarsal-Carpal Coalition Syndrome

Publications for Tarsal-Carpal Coalition Syndrome

Articles related to Tarsal-Carpal Coalition Syndrome:

(show all 13)
# Title Authors PMID Year
1
Identical mutations in NOG can cause either tarsal/carpal coalition syndrome or proximal symphalangism. 61 57 6
11545688 2001
2
Tarsal and carpal coalition and symphalangism of the Fuhrmann type. Report of a family. 57 6
4019538 1985
3
Heterozygous mutations in the gene encoding noggin affect human joint morphogenesis. 6
10080184 1999
4
Congenital malformation of the feet with low body height. A new syndrome, caused by an autosomal dominant gene. 57
589846 1977
5
Tarsal-carpal coalition syndrome: importance of early diagnosis. 61
31175114 2019
6
Tarsal-carpal coalition syndrome: Report of a novel missense mutation in NOG gene and phenotypic delineation. 61
29159868 2018
7
A novel nonsense mutation in the NOG gene causes familial NOG-related symphalangism spectrum disorder. 61
27508084 2016
8
Surgical Considerations for Massive Tarsal Coalitions in Multiple Synostosis Syndrome: A Case Report. 61
25799911 2015
9
Novel NOG mutation in Japanese patients with stapes ankylosis with broad thumbs and toes. 61
26211601 2015
10
A mutation in the heparin-binding site of noggin as a novel mechanism of proximal symphalangism and conductive hearing loss. 61
24735539 2014
11
[Tarsal-carpal coalition syndrome: a familial case]. 61
22326510 2012
12
A comprehensive review of reported heritable noggin-associated syndromes and proposed clinical utility of one broadly inclusive diagnostic term: NOG-related-symphalangism spectrum disorder (NOG-SSD). 61
21538686 2011
13
P35S mutation in the NOG gene associated with Teunissen-Cremers syndrome and features of multiple NOG joint-fusion syndromes. 61
18440889 2008

Variations for Tarsal-Carpal Coalition Syndrome

ClinVar genetic disease variations for Tarsal-Carpal Coalition Syndrome:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 NOG NM_005450.5(NOG):c.611G>T (p.Arg204Leu) SNV Pathogenic 6696 rs104894610 GRCh37: 17:54672195-54672195
GRCh38: 17:56594834-56594834
2 NOG NM_005450.5(NOG):c.104C>G (p.Pro35Arg) SNV Pathogenic 6697 rs104894611 GRCh37: 17:54671688-54671688
GRCh38: 17:56594327-56594327
3 NOG NM_005450.5(NOG):c.665A>G (p.Tyr222Cys) SNV Pathogenic 6691 rs104894602 GRCh37: 17:54672249-54672249
GRCh38: 17:56594888-56594888
4 NOG NM_005450.5(NOG):c.611G>A (p.Arg204Gln) SNV Likely pathogenic 375295 rs104894610 GRCh37: 17:54672195-54672195
GRCh38: 17:56594834-56594834
5 NOG NM_005450.5(NOG):c.611G>A (p.Arg204Gln) SNV Likely pathogenic 375295 rs104894610 GRCh37: 17:54672195-54672195
GRCh38: 17:56594834-56594834

UniProtKB/Swiss-Prot genetic disease variations for Tarsal-Carpal Coalition Syndrome:

72
# Symbol AA change Variation ID SNP ID
1 NOG p.Pro35Arg VAR_011361 rs104894611
2 NOG p.Tyr222Cys VAR_011365 rs104894602
3 NOG p.Arg204Leu VAR_018326 rs104894610

Expression for Tarsal-Carpal Coalition Syndrome

Search GEO for disease gene expression data for Tarsal-Carpal Coalition Syndrome.

Pathways for Tarsal-Carpal Coalition Syndrome

Pathways related to Tarsal-Carpal Coalition Syndrome according to KEGG:

36
# Name Kegg Source Accession
1 TGF-beta signaling pathway hsa04350

Pathways related to Tarsal-Carpal Coalition Syndrome according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.61 NOG CHRD ACVR1
2 11.3 NOG GDF5
3
Show member pathways
11.11 NOG CHRD
4 10.9 NOG GDF5 CHRD ACVR1
5 10.84 NOG GDF5

GO Terms for Tarsal-Carpal Coalition Syndrome

Biological processes related to Tarsal-Carpal Coalition Syndrome according to GeneCards Suite gene sharing:

(show all 18)
# Name GO ID Score Top Affiliating Genes
1 transforming growth factor beta receptor signaling pathway GO:0007179 9.58 GDF5 ACVR1
2 cartilage development GO:0051216 9.57 NOG GDF5
3 determination of left/right symmetry GO:0007368 9.56 NKX3-2 ACVR1
4 positive regulation of pathway-restricted SMAD protein phosphorylation GO:0010862 9.55 GDF5 ACVR1
5 dorsal/ventral pattern formation GO:0009953 9.54 NOG ACVR1
6 cellular response to BMP stimulus GO:0071773 9.52 NOG ACVR1
7 embryonic skeletal system development GO:0048706 9.51 NOG NKX3-2
8 skeletal system development GO:0001501 9.5 NOG NKX3-2 CHRD
9 ventricular septum morphogenesis GO:0060412 9.49 NOG ACVR1
10 mesoderm formation GO:0001707 9.48 NOG ACVR1
11 negative regulation of chondrocyte differentiation GO:0032331 9.46 NKX3-2 GDF5
12 middle ear morphogenesis GO:0042474 9.43 NOG NKX3-2
13 BMP signaling pathway GO:0030509 9.43 NOG GDF5 ACVR1
14 transmembrane receptor protein serine/threonine kinase signaling pathway GO:0007178 9.4 GDF5 ACVR1
15 endocardial cushion morphogenesis GO:0003203 9.37 NOG ACVR1
16 BMP signaling pathway involved in heart development GO:0061312 9.16 NOG ACVR1
17 negative regulation of osteoblast differentiation GO:0045668 9.13 NOG CRIM1 CHRD
18 negative regulation of BMP signaling pathway GO:0030514 8.8 NOG CRIM1 CHRD

Molecular functions related to Tarsal-Carpal Coalition Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytokine binding GO:0019955 8.62 NOG CHRD

Sources for Tarsal-Carpal Coalition Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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