DA1A
MCID: ART144
MIFTS: 44

Arthrogryposis, Distal, Type 1a (DA1A)

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

Aliases & Classifications for Arthrogryposis, Distal, Type 1a

MalaCards integrated aliases for Arthrogryposis, Distal, Type 1a:

Name: Arthrogryposis, Distal, Type 1a 57
Arthrogryposis Multiplex Congenita Distal Type 1 53 75 29 6
Amcd1 57 53 25 75
Distal Arthrogryposis Type 1b 53 29 6
Da1a 57 53 75
Arthrogryposis Multiplex Congenita, Distal, Type 1 57 13
Arthrogryposis, Distal, Type 1 57 25
Distal Arthrogryposis Type 1 53 25
Digitotalar Dysmorphism 53 73
Da1 57 25
Arthrogryposis Multiplex Congenita, Distal, Type I; Amcd1 57
Arthrogryposis Multiplex Congenita, Distal, Type I 57
Arthrogryposis Multiplex Congenita, Distal Type 1 76
Arthrogryposis, Distal, Type 1; Da1 57
Arthrogryposis Multiplex Congenita 75
Distal Arthrogryposis Type 1a 53
Arthrogryposis, Distal, 1a 75
Arthrogryposis 73
Amc 75

Characteristics:

OMIM:

57
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, distal, type 1a:
Inheritance heterogeneous autosomal dominant inheritance


Classifications:



Summaries for Arthrogryposis, Distal, Type 1a

OMIM : 57 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, Distal, Type 1a, also known as arthrogryposis multiplex congenita distal type 1, is related to distal arthrogryposis and digitotalar dysmorphism, and has symptoms including arthralgia, metatarsalgia and muscle cramp. An important gene associated with Arthrogryposis, Distal, Type 1a is TPM2 (Tropomyosin 2), and among its related pathways/superpathways are Cardiac conduction and Striated Muscle Contraction. The drugs Aripiprazole and Olanzapine have been mentioned in the context of this disorder. Related phenotypes are cryptorchidism and trismus

UniProtKB/Swiss-Prot : 75 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.

NIH Rare Diseases : 53 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.

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.

Wikipedia : 76 Arthrogryposis multiplex congenital (AMC), or simply arthrogryposis, describes congenital joint... more...

Related Diseases for Arthrogryposis, Distal, Type 1a

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



Diseases related to Arthrogryposis, Distal, Type 1a

Symptoms & Phenotypes for Arthrogryposis, Distal, Type 1a

Symptoms via clinical synopsis from OMIM:

57
Skeletal Feet:
talipes equinovarus
calcaneovalgus deformities
vertical talus

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

Neurologic Central Nervous System:
normal intelligence

Skeletal Spine:
mild scoliosis

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

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

Chest Ribs Sternum Clavicles And Scapulae:
stiff shoulders

Skeletal Limbs:
elbow flexion contractures
knee flexion contractures


Clinical features from OMIM:

108120

Human phenotypes related to Arthrogryposis, Distal, Type 1a:

32 (show all 20)
# Description HPO Frequency HPO Source Accession
1 cryptorchidism 32 HP:0000028
2 trismus 32 HP:0000211
3 single transverse palmar crease 32 HP:0000954
4 absent distal interphalangeal creases 32 HP:0001032
5 adducted thumb 32 HP:0001181
6 hand clenching 32 HP:0001188
7 ulnar deviation of the hand or of fingers of the hand 32 HP:0001193
8 congenital hip dislocation 32 HP:0001374
9 talipes equinovarus 32 HP:0001762
10 rocker bottom foot 32 HP:0001838
11 calcaneovalgus deformity 32 HP:0001848
12 scoliosis 32 HP:0002650
13 arthrogryposis multiplex congenita 32 HP:0002804
14 elbow flexion contracture 32 HP:0002987
15 decreased hip abduction 32 HP:0003184
16 hip contracture 32 HP:0003273
17 knee flexion contracture 32 HP:0006380
18 joint contracture of the hand 32 HP:0009473
19 stiff shoulders 32 HP:0009742
20 camptodactyly 32 HP:0012385

UMLS symptoms related to Arthrogryposis, Distal, Type 1a:


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

Drugs & Therapeutics for Arthrogryposis, Distal, Type 1a

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

(show all 34)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Aripiprazole Approved, Investigational Phase 4 129722-12-9 60795
2
Olanzapine Approved, Investigational Phase 4 132539-06-1 4585
3 Antipsychotic Agents Phase 4,Phase 1
4 Central Nervous System Depressants Phase 4,Phase 1
5 Neurotransmitter Agents Phase 4,Phase 1
6 Psychotropic Drugs Phase 4,Phase 1
7 Tranquilizing Agents Phase 4,Phase 1
8 Antiemetics Phase 4
9 Autonomic Agents Phase 4
10 Gastrointestinal Agents Phase 4
11 Neurotransmitter Uptake Inhibitors Phase 4
12 Peripheral Nervous System Agents Phase 4
13 Serotonin Agents Phase 4
14 Serotonin Uptake Inhibitors Phase 4
15
Serotonin Investigational, Nutraceutical Phase 4 50-67-9 5202
16
Cocaine Approved, Illicit Phase 1 50-36-2 5760 446220
17
Dopamine Approved Phase 1 51-61-6, 62-31-7 681
18 decanoic acid Phase 1
19 Dopamine Agents Phase 1
20 Dopamine Antagonists Phase 1
21 Flupenthixol decanoate Phase 1
22
Protein C Approved Not Applicable
23
Menthol Approved 2216-51-5 16666
24
Adenosine Approved, Investigational 58-61-7 60961
25
Serine Approved, Nutraceutical Not Applicable 56-45-1 5951
26 Alpha 1-Antitrypsin Not Applicable
27 HIV Protease Inhibitors Not Applicable
28
protease inhibitors Not Applicable
29 Protein C Inhibitor Not Applicable
30 Serine Proteinase Inhibitors Not Applicable
31 Trypsin Inhibitors Not Applicable
32 Analgesics
33 Anti-Arrhythmia Agents
34 Vasodilator Agents

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia Completed NCT00103571 Phase 4 Olanzapine;Aripiprazole
2 Infusion Laboratory: Protocol 5 (Flupenthixol) - 14 Unknown status NCT00000349 Phase 1 Flupenthixol
3 Polygen Defi-Alpha: Genetic Polymorphisms Study in Children With Alpha-1 Antitrypsin Deficiency, Included in the DEFI-ALPHA Cohort Recruiting NCT01862211 Not Applicable
4 Survey Study and Records Review of Treatment Outcomes in Freeman-Sheldon Syndrome Recruiting NCT01144741
5 Accuracy of Spircare Device as Compared to the Conventional Plethysmograph Enrolling by invitation NCT03056066
6 Study of Resting and Exercising Body Functioning in Freeman-Sheldon Syndrome and Related Conditions Not yet recruiting NCT01306994

Search NIH Clinical Center for Arthrogryposis, Distal, Type 1a

Genetic Tests for Arthrogryposis, Distal, Type 1a

Genetic tests related to Arthrogryposis, Distal, Type 1a:

# Genetic test Affiliating Genes
1 Arthrogryposis Multiplex Congenita Distal Type 1 29 TPM2
2 Distal Arthrogryposis Type 1b 29 MYBPC1

Anatomical Context for Arthrogryposis, Distal, Type 1a

Publications for Arthrogryposis, Distal, Type 1a

Articles related to Arthrogryposis, Distal, Type 1a:

# Title Authors Year
1
Findings, phenotypes, and outcomes in Freeman-Sheldon and Sheldon-Hall syndromes and distal arthrogryposis types 1 and 3: protocol for systematic review and patient-level data meta-analysis. ( 28264711 )
2017
2
A novel missense mutation of TNNI2 in a Chinese family cause distal arthrogryposis type 1. ( 26374086 )
2015
3
Spectrum of mutations that cause distal arthrogryposis types 1 and 2B. ( 23401156 )
2013
4
Exome sequencing identifies an MYH3 mutation in a family with distal arthrogryposis type 1. ( 21531865 )
2011
5
Myosin binding protein C1: a novel gene for autosomal dominant distal arthrogryposis type 1. ( 20045868 )
2010
6
Prenatal diagnosis of distal arthrogryposis type 1. ( 10384996 )
1999
7
Distal arthrogryposis type 1: clinical analysis of a large kindred. ( 8923936 )
1996

Variations for Arthrogryposis, Distal, Type 1a

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

75
# 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, Distal, Type 1a:

6
(show all 44)
# 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 TPM2 NM_003289.3(TPM2): c.271C> G (p.Arg91Gly) single nucleotide variant Pathogenic rs104894127 GRCh38 Chromosome 9, 35685750: 35685750
3 TPM2 NM_003289.3(TPM2): c.349G> A (p.Glu117Lys) single nucleotide variant Pathogenic rs104894129 GRCh37 Chromosome 9, 35685669: 35685669
4 TPM2 NM_003289.3(TPM2): c.349G> A (p.Glu117Lys) single nucleotide variant Pathogenic rs104894129 GRCh38 Chromosome 9, 35685672: 35685672
5 TPM2 NM_003289.3(TPM2): c.415_417delGAG (p.Glu139del) deletion Pathogenic rs199476153 GRCh37 Chromosome 9, 35685506: 35685508
6 TPM2 NM_003289.3(TPM2): c.415_417delGAG (p.Glu139del) deletion Pathogenic rs199476153 GRCh38 Chromosome 9, 35685509: 35685511
7 MYBPC1 NM_002465.3(MYBPC1): c.706T> C (p.Trp236Arg) single nucleotide variant Pathogenic rs387906657 GRCh37 Chromosome 12, 102036237: 102036237
8 MYBPC1 NM_002465.3(MYBPC1): c.706T> C (p.Trp236Arg) single nucleotide variant Pathogenic rs387906657 GRCh38 Chromosome 12, 101642459: 101642459
9 MYBPC1 NM_002465.3(MYBPC1): c.2566T> C (p.Tyr856His) single nucleotide variant Pathogenic rs387906658 GRCh37 Chromosome 12, 102064140: 102064140
10 MYBPC1 NM_002465.3(MYBPC1): c.2566T> C (p.Tyr856His) single nucleotide variant Pathogenic rs387906658 GRCh38 Chromosome 12, 101670362: 101670362
11 TPM2 NM_003289.3(TPM2): c.773-3delC deletion Uncertain significance rs727504179 GRCh37 Chromosome 9, 35683241: 35683241
12 TPM2 NM_003289.3(TPM2): c.773-3delC deletion Uncertain significance rs727504179 GRCh38 Chromosome 9, 35683244: 35683244
13 TPM2 NM_003289.3(TPM2): c.493-11_493-8delACTC deletion Benign/Likely benign rs528068364 GRCh37 Chromosome 9, 35685344: 35685347
14 TPM2 NM_003289.3(TPM2): c.493-11_493-8delACTC deletion Benign/Likely benign rs528068364 GRCh38 Chromosome 9, 35685347: 35685350
15 TPM2 NM_003289.3(TPM2): c.726C> T (p.Ala242=) single nucleotide variant Conflicting interpretations of pathogenicity rs76414035 GRCh37 Chromosome 9, 35684289: 35684289
16 TPM2 NM_003289.3(TPM2): c.726C> T (p.Ala242=) single nucleotide variant Conflicting interpretations of pathogenicity rs76414035 GRCh38 Chromosome 9, 35684292: 35684292
17 TPM2 NM_003289.3(TPM2): c.773-4_773-3insA insertion Benign/Likely benign rs886063905 GRCh37 Chromosome 9, 35683241: 35683242
18 TPM2 NM_003289.3(TPM2): c.773-4_773-3insA insertion Benign/Likely benign rs886063905 GRCh38 Chromosome 9, 35683244: 35683245
19 TPM2 NM_003289.3(TPM2): c.773-5_773-3dupCCC duplication Conflicting interpretations of pathogenicity rs35401252 GRCh38 Chromosome 9, 35683244: 35683246
20 TPM2 NM_003289.3(TPM2): c.773-5_773-3dupCCC duplication Conflicting interpretations of pathogenicity rs35401252 GRCh37 Chromosome 9, 35683241: 35683243
21 MET NM_000245.3(MET): c.3701A> G (p.Tyr1234Cys) single nucleotide variant risk factor GRCh38 Chromosome 7, 116783372: 116783372
22 MET NM_000245.3(MET): c.3701A> G (p.Tyr1234Cys) single nucleotide variant risk factor GRCh37 Chromosome 7, 116423426: 116423426
23 TPM2 NM_003289.3(TPM2): c.344_346delAGG (p.Glu115del) deletion Uncertain significance GRCh37 Chromosome 9, 35685672: 35685674
24 TPM2 NM_003289.3(TPM2): c.344_346delAGG (p.Glu115del) deletion Uncertain significance GRCh38 Chromosome 9, 35685675: 35685677
25 TPM2 NM_003289.3(TPM2): c.703-3dup duplication Uncertain significance GRCh37 Chromosome 9, 35684315: 35684315
26 TPM2 NM_003289.3(TPM2): c.703-3dup duplication Uncertain significance GRCh38 Chromosome 9, 35684318: 35684318
27 TPM2 NM_003289.3(TPM2): c.635A> G (p.Asp212Gly) single nucleotide variant Uncertain significance GRCh37 Chromosome 9, 35684733: 35684733
28 TPM2 NM_003289.3(TPM2): c.635A> G (p.Asp212Gly) single nucleotide variant Uncertain significance GRCh38 Chromosome 9, 35684736: 35684736
29 TPM2 NM_003289.3(TPM2): c.729G> A (p.Glu243=) single nucleotide variant Likely benign rs751675623 GRCh38 Chromosome 9, 35684289: 35684289
30 TPM2 NM_003289.3(TPM2): c.729G> A (p.Glu243=) single nucleotide variant Likely benign rs751675623 GRCh37 Chromosome 9, 35684286: 35684286
31 TPM2 NM_003289.3(TPM2): c.536C> T (p.Ser179Leu) single nucleotide variant Uncertain significance rs150120234 GRCh37 Chromosome 9, 35685293: 35685293
32 TPM2 NM_003289.3(TPM2): c.536C> T (p.Ser179Leu) single nucleotide variant Uncertain significance rs150120234 GRCh38 Chromosome 9, 35685296: 35685296
33 TPM2 NM_003289.3(TPM2): c.374+9G> C single nucleotide variant Likely benign rs200730708 GRCh38 Chromosome 9, 35685638: 35685638
34 TPM2 NM_003289.3(TPM2): c.374+9G> C single nucleotide variant Likely benign rs200730708 GRCh37 Chromosome 9, 35685635: 35685635
35 TPM2 NM_003289.3(TPM2): c.363_365delTGA (p.Asp121del) deletion Likely pathogenic GRCh38 Chromosome 9, 35685656: 35685658
36 TPM2 NM_003289.3(TPM2): c.363_365delTGA (p.Asp121del) deletion Likely pathogenic GRCh37 Chromosome 9, 35685653: 35685655
37 TPM2 NM_003289.3(TPM2): c.357G> A (p.Ala119=) single nucleotide variant Likely benign rs376028030 GRCh37 Chromosome 9, 35685661: 35685661
38 TPM2 NM_003289.3(TPM2): c.357G> A (p.Ala119=) single nucleotide variant Likely benign rs376028030 GRCh38 Chromosome 9, 35685664: 35685664
39 TPM2 NM_003289.3(TPM2): c.81C> A (p.Ala27=) single nucleotide variant Likely benign rs564977715 GRCh37 Chromosome 9, 35689734: 35689734
40 TPM2 NM_003289.3(TPM2): c.81C> A (p.Ala27=) single nucleotide variant Likely benign rs564977715 GRCh38 Chromosome 9, 35689737: 35689737
41 TPM2 NM_003289.3(TPM2): c.633G> A (p.Ala211=) single nucleotide variant Likely benign rs199758432 GRCh37 Chromosome 9, 35684735: 35684735
42 TPM2 NM_003289.3(TPM2): c.633G> A (p.Ala211=) single nucleotide variant Likely benign rs199758432 GRCh38 Chromosome 9, 35684738: 35684738
43 TPM2 NM_003289.3(TPM2): c.747G> A (p.Leu249=) single nucleotide variant Likely benign GRCh37 Chromosome 9, 35684268: 35684268
44 TPM2 NM_003289.3(TPM2): c.747G> A (p.Leu249=) single nucleotide variant Likely benign GRCh38 Chromosome 9, 35684271: 35684271

Expression for Arthrogryposis, Distal, Type 1a

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

Pathways for Arthrogryposis, Distal, Type 1a

GO Terms for Arthrogryposis, Distal, Type 1a

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

# Name GO ID Score Top Affiliating Genes
1 actin filament organization GO:0007015 9.16 MYBPC1 TPM2
2 muscle contraction GO:0006936 8.96 MYBPC1 TPM2
3 muscle filament sliding GO:0030049 8.62 MYBPC1 TPM2

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

# Name GO ID Score Top Affiliating Genes
1 actin filament binding GO:0051015 8.96 MYBPC1 TPM2
2 structural constituent of muscle GO:0008307 8.62 MYBPC1 TPM2

Sources for Arthrogryposis, Distal, Type 1a

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 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 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
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54 NINDS
55 Novoseek
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58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
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74 UMLS via Orphanet
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