MCID: ART121
MIFTS: 43

Arthrogryposis Multiplex Congenita, Distal, Type 1

Categories: Genetic diseases, Rare diseases, Fetal diseases

Aliases & Classifications for Arthrogryposis Multiplex Congenita, Distal, Type 1

MalaCards integrated aliases for Arthrogryposis Multiplex Congenita, Distal, Type 1:

Name: Arthrogryposis Multiplex Congenita, Distal, Type 1 54 24 13
Distal Arthrogryposis Type 1 50 24 25 56
Arthrogryposis Multiplex Congenita Distal Type 1 50 71 29
Digitotalar Dysmorphism 50 56 69
Amcd1 50 25 71
Da1a 50 56 71
Distal Arthrogryposis Type 1b 50 29
Da1 25 56
Arthrogryposis Multiplex Congenita 71
Arthrogryposis, Distal, Type 1 25
Distal Arthrogryposis Type 1a 50
Arthrogryposis, Distal, 1a 71
Arthrogryposis 69
Amc 71

Characteristics:

Orphanet epidemiological data:

56
digitotalar dysmorphism
Inheritance: Autosomal dominant; Age of onset: Neonatal; Age of death: normal life expectancy;

OMIM:

54
Inheritance:
autosomal dominant

Miscellaneous:
marked intrafamilial and interfamilial variability
most frequently affected joints - hands (98%) and feet (88%)
genetic heterogeneity (see 601680)


HPO:

32
arthrogryposis multiplex congenita, distal, type 1:
Inheritance heterogeneous autosomal dominant inheritance


Classifications:



Summaries for Arthrogryposis Multiplex Congenita, Distal, Type 1

OMIM : 54
In general, the distal arthrogryposes are a group of disorders characterized by contractures mainly involving the distal parts of the limbs. The hands have a characteristic position with medially overlapping fingers, clenched fists, ulnar deviation of fingers, and camptodactyly, and the feet have deformities. Contractures at other joints are variable; there are no associated visceral anomalies, and intelligence is normal. Classically, DA was defined as being without overt neurologic or muscle disease (Lin et al., 1977 and Hall et al., 1982), although more recent evidence suggests that DA1A due to TPM2 mutations results from muscle dysfunction (Robinson et al., 2007; Mokbel et al., 2013; Davidson et al., 2013). The prototypic distal arthrogryposis is type 1 (DA1), which is characterized largely by camptodactyly and clubfoot. Hypoplasia and/or absence of some interphalangeal creases is common. The shoulders and hips are less frequently affected. While the pattern of affected joints is consistent, the degree to which the joints are affected is highly variable, with equinovarus deformities ranging from mild to severe and hand involvement ranging from isolated hypoplasia of the distal interphalangeal crease of the fifth digit to severely clenched fists and ulnar deviation of the wrist. The various phenotypic forms of distal arthrogryposis are classified hierarchically according to the proportion of features they share with one another and are designated DA1 through DA10 (summary by Bamshad et al., 2009). Bamshad et al. (1996) revised the classification by Hall et al. (1982) of the common mendelian arthrogryposis syndromes. Krakowiak et al. (1997) provided a useful classification of the distal arthrogryposes. (108120)

MalaCards based summary : Arthrogryposis Multiplex Congenita, Distal, Type 1, also known as distal arthrogryposis type 1, is related to neurogenic arthrogryposis multiplex congenita and arthrogryposis multiplex congenita, neurogenic, with myelin defect, and has symptoms including joint stiffness, overlapping fingers and talipes. An important gene associated with Arthrogryposis Multiplex Congenita, Distal, Type 1 is TPM2 (Tropomyosin 2 (Beta)), and among its related pathways/superpathways are Cardiac conduction and Striated Muscle Contraction. The drugs Adenosine and Menthol have been mentioned in the context of this disorder. Affiliated tissues include bone.

NIH Rare Diseases : 50 the following summary is from orphanet, a european reference portal for information on rare diseases and orphan drugs.orpha number: 1146disease definitiondigitotalar dysmorphism, also known as distal arthrogryposis type 1 (da1), is an autosomal dominantcongenital anomaly characterized by contractures of the distal regions of the hands and feet with no facial involvement or any additional anomalies. it is the most common type of distal arthrogryposis (see this term).visit the orphanet disease page for more resources. last updated: 6/10/2014

UniProtKB/Swiss-Prot : 71 Arthrogryposis, distal, 1A: A form of distal arthrogryposis, a disease characterized by congenital joint contractures that mainly involve two or more distal parts of the limbs, in the absence of a primary neurological or muscle disease. Distal arthrogryposis type 1 is characterized largely by camptodactyly and clubfoot. Hypoplasia and/or absence of some interphalangeal creases is common. The shoulders and hips are less frequently affected.

Genetics Home Reference : 25 Distal arthrogryposis type 1 is a disorder characterized by joint deformities (contractures) that restrict movement in the hands and feet. The term "arthrogryposis" comes from the Greek words for joint (arthro-) and crooked or hooked (gryposis). The characteristic features of this condition include permanently bent fingers and toes (camptodactyly), overlapping fingers, and a hand deformity in which all of the fingers are angled outward toward the fifth finger (ulnar deviation). Clubfoot, which is an inward- and upward-turning foot, is also commonly seen with distal arthrogryposis type 1. The specific hand and foot abnormalities vary among affected individuals. However, this condition typically does not cause any signs and symptoms affecting other parts of the body.

Related Diseases for Arthrogryposis Multiplex Congenita, Distal, Type 1

Diseases in the Arthrogryposis Multiplex Congenita, Distal, Type 1 family:

Myh3-Related Arthrogryposis Multiplex Congenita, Distal, Type 2b Tnni2-Related Arthrogryposis Multiplex Congenita, Distal, Type 2b
Tnnt3-Related Arthrogryposis Multiplex Congenita, Distal, Type 2b Tpm2-Related Arthrogryposis Multiplex Congenita, Distal, Type 2b

Diseases related to Arthrogryposis Multiplex Congenita, Distal, Type 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 21)
id Related Disease Score Top Affiliating Genes
1 neurogenic arthrogryposis multiplex congenita 12.6
2 arthrogryposis multiplex congenita, neurogenic, with myelin defect 12.4
3 arthrogryposis multiplex congenita whistling face 12.4
4 autosomal recessive myogenic arthrogryposis multiplex congenita 12.3
5 spinal muscular atrophy, x-linked 2, infantile 11.5
6 arthrogryposis, distal, type 1b 10.9
7 arthrogryposis, distal, type 5d 10.8
8 arthrogryposis, distal, type 5 10.8
9 distal arthrogryposis 10.2
10 uterine corpus endometrial stromal sarcoma 9.8 RYR1 TPM2
11 benign hypertensive renal disease 9.7 TNNI2 TNNT3
12 3p- syndrome 9.6 MYH3 RYR1 TPM2
13 cholesteatoma of attic 9.6 TNNI2 TNNT3
14 clear cell sarcoma 9.5 RYR1 TNNI2 TPM2
15 nephrotic syndrome 9.3 MYBPC1 MYH3 TNNT3 TPM2
16 congenital cystic eye multiple ocular and intracranial anomalies 9.2 NALCN RYR1 TNNT3
17 microcephaly and chorioretinopathy 1 9.1 RYR1 TNNI2 TNNT3 TPM2
18 arthrogryposis, distal, type 3 9.0 MYH3 TNNI2 TNNT3 TPM2
19 nemaline myopathy 4, autosomal dominant 8.2 MYH3 NALCN TNNI2 TNNT3 TPM2
20 arthrogryposis, distal, type 2b 7.0 ADGRG6 MYBPC1 MYH3 NALCN RYR1 TNNI2
21 familial atrial fibrillation 7.0 ADGRG6 MYBPC1 MYH3 NALCN RYR1 TNNI2

Graphical network of the top 20 diseases related to Arthrogryposis Multiplex Congenita, Distal, Type 1:



Diseases related to Arthrogryposis Multiplex Congenita, Distal, Type 1

Symptoms & Phenotypes for Arthrogryposis Multiplex Congenita, Distal, Type 1

Symptoms via clinical synopsis from OMIM:

54

Skeletal- Feet:
talipes equinovarus
vertical talus
calcaneovalgus deformities

Skeletal- Pelvis:
hip flexion contractures
congenital hip dislocations
decreased hip abduction

Skeletal- Hands:
absent distal interphalangeal creases
single transverse palmar creases
tightly clenched fists (neonate)
camptodactyly (adult)
ulnar deviation (adult)

Chest- Ribs Sternum Clavicles And Scapulae:
stiff shoulders

Neurologic- Central Nervous System:
normal intelligence

Skin Nails & Hair- Skin:
absent distal interphalangeal creases
single transverse palmar creases

Skeletal- Limbs:
elbow flexion contractures
knee flexion contractures

Skeletal- Spine:
mild scoliosis


Clinical features from OMIM:

108120

Human phenotypes related to Arthrogryposis Multiplex Congenita, Distal, Type 1:

56 32 (show all 28)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 joint stiffness 56 32 frequent (33%) Frequent (79-30%) HP:0001387
2 overlapping fingers 56 32 hallmark (90%) Very frequent (99-80%) HP:0010557
3 talipes 56 32 frequent (33%) Frequent (79-30%) HP:0001883
4 narrow mouth 56 32 occasional (7.5%) Occasional (29-5%) HP:0000160
5 adducted thumb 56 32 very rare (1%) Very frequent (99-80%) HP:0001181
6 abnormality of the hip bone 56 32 occasional (7.5%) Occasional (29-5%) HP:0003272
7 camptodactyly of finger 56 32 frequent (33%) Frequent (79-30%) HP:0100490
8 ulnar deviation of finger 56 32 frequent (33%) Frequent (79-30%) HP:0009465
9 rocker bottom foot 56 32 very rare (1%) Occasional (29-5%) HP:0001838
10 scoliosis 32 very rare (1%) HP:0002650
11 arthrogryposis multiplex congenita 32 HP:0002804
12 cryptorchidism 32 very rare (1%) HP:0000028
13 camptodactyly 32 HP:0012385
14 talipes equinovarus 32 very rare (1%) HP:0001762
15 elbow flexion contracture 32 HP:0002987
16 knee flexion contracture 32 very rare (1%) HP:0006380
17 trismus 32 very rare (1%) HP:0000211
18 congenital hip dislocation 32 very rare (1%) HP:0001374
19 absent distal interphalangeal creases 32 very rare (1%) HP:0001032
20 calcaneovalgus deformity 32 very rare (1%) HP:0001848
21 single transverse palmar crease 32 very rare (1%) HP:0000954
22 stiff shoulders 32 very rare (1%) HP:0009742
23 decreased hip abduction 32 very rare (1%) HP:0003184
24 hip contracture 32 very rare (1%) HP:0003273
25 hand clenching 32 very rare (1%) HP:0001188
26 mild short stature 32 HP:0003502
27 joint contracture of the hand 32 very rare (1%) HP:0009473
28 ulnar deviation of the hand or of fingers of the hand 32 very rare (1%) HP:0001193

UMLS symptoms related to Arthrogryposis Multiplex Congenita, Distal, Type 1:


arthralgia, metatarsalgia, muscle cramp, muscle rigidity, muscle spasticity, muscle weakness, myalgia

Drugs & Therapeutics for Arthrogryposis Multiplex Congenita, Distal, Type 1

Drugs for Arthrogryposis Multiplex Congenita, Distal, Type 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 7)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Adenosine Approved, Investigational 58-61-7 60961
2
Menthol Approved 2216-51-5 16666
3 Analgesics
4 Anti-Arrhythmia Agents
5 Neurotransmitter Agents
6 Peripheral Nervous System Agents
7 Vasodilator Agents

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Study of Resting and Exercising Body Functioning in Freeman-Sheldon Syndrome and Related Conditions Unknown status NCT01306994
2 Survey Study and Records Review of Treatment Outcomes in Freeman-Sheldon Syndrome Recruiting NCT01144741

Search NIH Clinical Center for Arthrogryposis Multiplex Congenita, Distal, Type 1

Genetic Tests for Arthrogryposis Multiplex Congenita, Distal, Type 1

Genetic tests related to Arthrogryposis Multiplex Congenita, Distal, Type 1:

id Genetic test Affiliating Genes
1 Arthrogryposis Multiplex Congenita Distal Type 1 29
2 Distal Arthrogryposis Type 1b 29
3 Arthrogryposis Multiplex Congenita, Distal, Type 1 24 TPM2

Anatomical Context for Arthrogryposis Multiplex Congenita, Distal, Type 1

MalaCards organs/tissues related to Arthrogryposis Multiplex Congenita, Distal, Type 1:

39
Bone

Publications for Arthrogryposis Multiplex Congenita, Distal, Type 1

Variations for Arthrogryposis Multiplex Congenita, Distal, Type 1

UniProtKB/Swiss-Prot genetic disease variations for Arthrogryposis Multiplex Congenita, Distal, Type 1:

71
id Symbol AA change Variation ID SNP ID
1 TPM2 p.Arg91Gly VAR_016086 rs104894127
2 TPM2 p.Arg133Trp VAR_070981 rs137853305
3 TPM2 p.Gln93Arg VAR_071490 rs199476151
4 TPM2 p.Glu117Lys VAR_071491 rs104894129
5 TPM2 p.Tyr261Cys VAR_071498

ClinVar genetic disease variations for Arthrogryposis Multiplex Congenita, Distal, Type 1:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 TPM2 NM_003289.3(TPM2): c.271C> G (p.Arg91Gly) single nucleotide variant Pathogenic rs104894127 GRCh37 Chromosome 9, 35685747: 35685747
2 MYBPC1 NM_002465.3(MYBPC1): c.706T> C (p.Trp236Arg) single nucleotide variant Pathogenic rs387906657 GRCh37 Chromosome 12, 102036237: 102036237
3 MYBPC1 NM_002465.3(MYBPC1): c.2566T> C (p.Tyr856His) single nucleotide variant Pathogenic rs387906658 GRCh37 Chromosome 12, 102064140: 102064140
4 ADGRG6 NM_198569.2(ADGRG6): c.19C> T (p.Arg7Ter) single nucleotide variant Pathogenic rs749355583 GRCh37 Chromosome 6, 142630697: 142630697
5 ADGRG6 NM_020455.5(ADGRG6): c.2144dupG (p.Gln716Thrfs) duplication Pathogenic rs793888524 GRCh37 Chromosome 6, 142726841: 142726841
6 ADGRG6 NM_198569.2(ADGRG6): c.2306T> A (p.Val769Glu) single nucleotide variant Pathogenic rs793888525 GRCh37 Chromosome 6, 142729324: 142729324
7 RYR1 NM_000540.2(RYR1): c.10620C> G (p.Tyr3540Ter) single nucleotide variant Pathogenic rs758247804 GRCh38 Chromosome 19, 38525496: 38525496

Expression for Arthrogryposis Multiplex Congenita, Distal, Type 1

Search GEO for disease gene expression data for Arthrogryposis Multiplex Congenita, Distal, Type 1.

Pathways for Arthrogryposis Multiplex Congenita, Distal, Type 1

GO Terms for Arthrogryposis Multiplex Congenita, Distal, Type 1

Cellular components related to Arthrogryposis Multiplex Congenita, Distal, Type 1 according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 myofibril GO:0030016 9.26 MYBPC1 MYH3
2 muscle myosin complex GO:0005859 9.16 MYBPC1 MYH3
3 myosin filament GO:0032982 8.96 MYBPC1 MYH3
4 troponin complex GO:0005861 8.62 TNNI2 TNNT3

Biological processes related to Arthrogryposis Multiplex Congenita, Distal, Type 1 according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 muscle contraction GO:0006936 9.43 MYBPC1 RYR1 TPM2
2 actin filament organization GO:0007015 9.4 MYBPC1 TPM2
3 sarcomere organization GO:0045214 9.37 MYBPC1 MYH3
4 regulation of muscle contraction GO:0006937 9.32 TNNI2 TNNT3
5 regulation of ATPase activity GO:0043462 9.16 TNNT3 TPM2
6 skeletal muscle contraction GO:0003009 9.13 MYH3 TNNI2 TNNT3
7 muscle filament sliding GO:0030049 9.02 MYBPC1 MYH3 TNNI2 TNNT3 TPM2

Molecular functions related to Arthrogryposis Multiplex Congenita, Distal, Type 1 according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 structural constituent of muscle GO:0008307 9.16 MYBPC1 TPM2
2 actin filament binding GO:0051015 9.13 MYBPC1 MYH3 TPM2
3 actin binding GO:0003779 8.92 MYH3 TNNI2 TNNT3 TPM2

Sources for Arthrogryposis Multiplex Congenita, Distal, Type 1

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 HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
Content
Loading form....