MCID: ART117
MIFTS: 38

Arthrogryposis, Distal, Type 2b

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

Aliases & Classifications for Arthrogryposis, Distal, Type 2b

MalaCards integrated aliases for Arthrogryposis, Distal, Type 2b:

Name: Arthrogryposis, Distal, Type 2b 54 69
Arthrogryposis Multiplex Congenita, Distal, Type 2b 54 24 25 13
Sheldon-Hall Syndrome 24 25 56 71
Distal Arthrogryposis Type 2b 24 25 56
Da2b 24 25 71
Freeman-Sheldon Syndrome Variant 56 71
Shs 25 71
Arthrogryposis Multiplex Congenita Distal Type Ii with Craniofacial Abnormalities 71
Arthrogryposis Multiplex Congenita, Distal, Type Iib 24
Arthrogryposis Multiplex Congenita Distal Type 2b 71
Freeman- Sheldon Syndrome Variant 24
Arthrogryposis, Distal, 2b 71
Amcd2b 71
Fssv 71

Characteristics:

Orphanet epidemiological data:

56
sheldon-hall syndrome
Inheritance: Autosomal dominant,Not applicable; Age of onset: Neonatal; Age of death: normal life expectancy;

OMIM:

54
Inheritance:
autosomal dominant


HPO:

32
arthrogryposis, distal, type 2b:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Arthrogryposis, Distal, Type 2b

OMIM : 54
Distal arthrogryposis is a clinically and genetically heterogeneous disorder characterized by clenched fist, overlapping fingers, camptodactyly, ulnar deviation, and positional foot deformities from birth. It is a disorder of primary limb malformation without primary neurologic or muscle disease. DA1 is not associated with other abnormalities, whereas other forms of DA have additional phenotypic features (Bamshad et al., 1996). The congenital contractures in DA2B (Sheldon-Hall syndrome, SHS) are similar to those observed in DA1, but affected individuals tend to have more prominent nasolabial folds, downslanting palpebral fissures, and a small mouth. DA2B is thought to be the most common of the distal arthrogryposis disorders (summary by Bamshad et al., 2009). For a general phenotypic description and a discussion of genetic heterogeneity of distal arthrogryposis, see DA1 (108120). (601680)

MalaCards based summary : Arthrogryposis, Distal, Type 2b, also known as arthrogryposis multiplex congenita, distal, type 2b, is related to distal arthrogryposis and tpm2-related arthrogryposis multiplex congenita, distal, type 2b, and has symptoms including short stature, scoliosis and micrognathia. An important gene associated with Arthrogryposis, Distal, Type 2b is TNNT3 (Troponin T3, Fast Skeletal Type), and among its related pathways/superpathways are Cardiac conduction and Striated Muscle Contraction. The drug Menthol has been mentioned in the context of this disorder. Affiliated tissues include bone.

Genetics Home Reference : 25 Sheldon-Hall syndrome, also known as distal arthrogryposis type 2B, 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). "Distal" refers to areas of the body away from the center. The characteristic features of this condition include permanently bent fingers and toes (camptodactyly), overlapping fingers, and a hand deformity called ulnar deviation in which all of the fingers are angled outward toward the fifth (pinky) finger. Inward- and upward-turning feet (a condition called clubfoot) is also commonly seen in Sheldon-Hall syndrome. The specific hand and foot abnormalities vary among affected individuals; the abnormalities are present at birth and generally do not get worse over time.

UniProtKB/Swiss-Prot : 71 Arthrogryposis, distal, 2B: 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. DA2B is characterized by contractures of the hands and feet, and a distinctive face characterized by prominent nasolabial folds, small mouth and downslanting palpebral fissures.

Related Diseases for Arthrogryposis, Distal, Type 2b

Diseases in the Distal Arthrogryposis family:

Arthrogryposis, Distal, Type 10 Arthrogryposis, Distal, Type 5d
Arthrogryposis, Distal, Type 2b Arthrogryposis, Distal, Type 1b
Arthrogryposis, Distal, Type 2a Arthrogryposis, Distal, Type 8
Arthrogryposis, Distal, Type 5 Arthrogryposis, Distal, Type 3
Arthrogryposis, Distal, Type 6 Arthrogryposis, Distal, Type 4

Diseases related to Arthrogryposis, Distal, Type 2b via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 38)
id Related Disease Score Top Affiliating Genes
1 distal arthrogryposis 11.1
2 tpm2-related arthrogryposis multiplex congenita, distal, type 2b 11.1
3 renpenning syndrome 10.8
4 neuroblastoma 10.6
5 neuronitis 10.1
6 mumps 10.0
7 dysentery 10.0
8 neuropathy 9.8
9 congenital cystic eye multiple ocular and intracranial anomalies 9.8 NALCN TNNT3
10 endotheliitis 9.8
11 hepatic coma 9.8
12 cataract 9.8
13 hepatitis 9.8
14 senile cataract 9.8
15 benign hypertensive renal disease 9.6 TNNI2 TNNT3
16 glioma 9.6
17 gastric ulcer 9.6
18 infantile digital fibromatosis 9.6
19 pertussis 9.6
20 mercury poisoning 9.6
21 esophagitis 9.6
22 cervicitis 9.6
23 sick building syndrome 9.6
24 breast disease 9.6
25 brain stem infarction 9.6
26 hiv-1 9.6
27 sclerosing hemangioma 9.6
28 diabetic neuropathy 9.6
29 herpes simplex 9.6
30 hemangioma 9.6
31 fibromatosis 9.6
32 cholesteatoma of attic 9.6 TNNI2 TNNT3
33 3p- syndrome 9.4 MYH3 TPM2
34 nephrotic syndrome 9.4 MYH3 TNNT3 TPM2
35 microcephaly and chorioretinopathy 1 9.2 TNNI2 TNNT3 TPM2
36 arthrogryposis, distal, type 3 8.6 MYH3 TNNI2 TNNT3 TPM2
37 nemaline myopathy 4, autosomal dominant 8.1 MYH3 NALCN TNNI2 TNNT3 TPM2
38 familial atrial fibrillation 8.1 MYH3 NALCN TNNI2 TNNT3 TPM2

Graphical network of the top 20 diseases related to Arthrogryposis, Distal, Type 2b:



Diseases related to Arthrogryposis, Distal, Type 2b

Symptoms & Phenotypes for Arthrogryposis, Distal, Type 2b

Symptoms via clinical synopsis from OMIM:

54

Growth- Height:
short stature

Skeletal:
joint contractures
precocious arthrosis

Head And Neck- Face:
micrognathia
long philtrum
small mandible
triangular face
small, prominent chin

Skeletal- Feet:
talipes equinovarus
vertical talus
metatarsus varus
clubfoot
calcaneovalgus deformities

Skeletal- Spine:
scoliosis (less common)

Head And Neck- Ears:
attached ear lobules

Head And Neck- Mouth:
high-arched palate
small mouth

Head And Neck- Eyes:
downslanting palpebral fissures

Head And Neck- Nose:
broad nasal root
broad nasal bridge
prominent nasolabial folds

Head And Neck- Neck:
webbed neck

Skeletal- Hands:
severe camptodactyly
ulnar deviation
overriding fingers (neonate)
thumb adduction
contractures of the proximal interphalangeal (pip) joints
more
Skeletal- Limbs:
ulnar wrist deviation


Clinical features from OMIM:

601680

Human phenotypes related to Arthrogryposis, Distal, Type 2b:

56 32 (show all 36)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 short stature 56 32 frequent (33%) Frequent (79-30%) HP:0004322
2 scoliosis 56 32 hallmark (90%) Very frequent (99-80%) HP:0002650
3 micrognathia 56 32 frequent (33%) Frequent (79-30%) HP:0000347
4 short neck 56 32 frequent (33%) Frequent (79-30%) HP:0000470
5 wide nasal bridge 56 32 frequent (33%) Frequent (79-30%) HP:0000431
6 webbed neck 56 32 hallmark (90%) Very frequent (99-80%) HP:0000465
7 joint stiffness 56 32 hallmark (90%) Very frequent (99-80%) HP:0001387
8 narrow face 56 32 frequent (33%) Frequent (79-30%) HP:0000275
9 high palate 56 32 frequent (33%) Frequent (79-30%) HP:0000218
10 overlapping fingers 56 32 frequent (33%) Frequent (79-30%) HP:0010557
11 ulnar deviation of the wrist 56 32 frequent (33%) Frequent (79-30%) HP:0003049
12 tarsal synostosis 56 32 frequent (33%) Frequent (79-30%) HP:0008368
13 bilateral single transverse palmar creases 56 32 hallmark (90%) Very frequent (99-80%) HP:0007598
14 adducted thumb 56 32 hallmark (90%) Very frequent (99-80%) HP:0001181
15 abnormality of the hip bone 56 32 frequent (33%) Frequent (79-30%) HP:0003272
16 protruding ear 56 32 frequent (33%) Frequent (79-30%) HP:0000411
17 round ear 56 32 frequent (33%) Frequent (79-30%) HP:0100830
18 vertebral segmentation defect 56 32 frequent (33%) Frequent (79-30%) HP:0003422
19 ulnar deviation of finger 56 32 frequent (33%) Frequent (79-30%) HP:0009465
20 aplasia/hypoplasia of the radius 56 32 hallmark (90%) Very frequent (99-80%) HP:0006501
21 arthrogryposis multiplex congenita 32 HP:0002804
22 talipes equinovarus 32 HP:0001762
23 long philtrum 32 HP:0000343
24 triangular face 32 HP:0000325
25 downslanted palpebral fissures 32 HP:0000494
26 metatarsus adductus 32 HP:0001840
27 calcaneovalgus deformity 32 HP:0001848
28 narrow mouth 32 HP:0000160
29 distal arthrogryposis 32 HP:0005684
30 mandibular prognathia 32 HP:0000303
31 camptodactyly of finger 32 HP:0100490
32 rocker bottom foot 32 HP:0001838
33 abnormality of the ear 32 HP:0000598
34 prominent nasolabial fold 32 HP:0005272
35 ulnar deviation of the hand or of fingers of the hand 32 HP:0001193
36 absent phalangeal crease 32 HP:0006109

UMLS symptoms related to Arthrogryposis, Distal, Type 2b:


ulnar deviation of the wrist

Drugs & Therapeutics for Arthrogryposis, Distal, Type 2b

Drugs for Arthrogryposis, Distal, Type 2b (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Menthol Approved 2216-51-5 16666

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Survey Study and Records Review of Treatment Outcomes in Freeman-Sheldon Syndrome Recruiting NCT01144741

Search NIH Clinical Center for Arthrogryposis, Distal, Type 2b

Genetic Tests for Arthrogryposis, Distal, Type 2b

Genetic tests related to Arthrogryposis, Distal, Type 2b:

id Genetic test Affiliating Genes
1 Arthrogryposis Multiplex Congenita, Distal, Type 2b 24 TNNT3

Anatomical Context for Arthrogryposis, Distal, Type 2b

MalaCards organs/tissues related to Arthrogryposis, Distal, Type 2b:

39
Bone

Publications for Arthrogryposis, Distal, Type 2b

Variations for Arthrogryposis, Distal, Type 2b

UniProtKB/Swiss-Prot genetic disease variations for Arthrogryposis, Distal, Type 2b:

71
id Symbol AA change Variation ID SNP ID
1 MYH3 p.Thr178Ile VAR_030370 rs121913619
2 MYH3 p.Ser261Phe VAR_030371
3 MYH3 p.Ser292Cys VAR_030372 rs139480342
4 MYH3 p.Glu375Lys VAR_030373 rs121913621
5 MYH3 p.Asp517Tyr VAR_030375
6 MYH3 p.Gly769Val VAR_030379
7 MYH3 p.Lys838Glu VAR_030381
8 TNNI2 p.Arg174Gln VAR_016087 rs104894311
9 TNNT3 p.Arg74His VAR_026453 rs121434638
10 TPM2 p.Arg133Trp VAR_070981 rs137853305

ClinVar genetic disease variations for Arthrogryposis, Distal, Type 2b:

6 (show all 15)
id Gene Variation Type Significance SNP ID Assembly Location
1 TNNT3 NM_006757.3(TNNT3): c.188G> A (p.Arg63His) single nucleotide variant Pathogenic rs121434638 GRCh37 Chromosome 11, 1954967: 1954967
2 TNNI2 NM_003282.3(TNNI2): c.521G> A (p.Arg174Gln) single nucleotide variant Pathogenic rs104894311 GRCh37 Chromosome 11, 1862753: 1862753
3 TNNI2 NM_003282.3(TNNI2): c.466C> T (p.Arg156Ter) single nucleotide variant Pathogenic rs104894312 GRCh37 Chromosome 11, 1862698: 1862698
4 TNNI2 NM_003282.3(TNNI2): c.499_501delGAG (p.Glu167del) deletion Pathogenic rs199474800 GRCh37 Chromosome 11, 1862731: 1862733
5 TPM2 NM_003289.3(TPM2): c.397C> T (p.Arg133Trp) single nucleotide variant Pathogenic rs137853305 GRCh37 Chromosome 9, 35685526: 35685526
6 MYH3 NM_002470.3(MYH3): c.2015G> A (p.Arg672His) single nucleotide variant Pathogenic rs121913617 GRCh37 Chromosome 17, 10544634: 10544634
7 MYH3 NM_002470.3(MYH3): c.2014C> T (p.Arg672Cys) single nucleotide variant Pathogenic rs121913618 GRCh37 Chromosome 17, 10544635: 10544635
8 MYH3 NM_002470.3(MYH3): c.533C> T (p.Thr178Ile) single nucleotide variant Pathogenic rs121913619 GRCh37 Chromosome 17, 10553691: 10553691
9 MYH3 NM_002470.3(MYH3): c.2474T> A (p.Val825Asp) single nucleotide variant Pathogenic rs121913620 GRCh37 Chromosome 17, 10543521: 10543521
10 MYH3 NM_002470.3(MYH3): c.2590_2592delCTC (p.Leu864del) deletion Pathogenic rs879255230 GRCh37 Chromosome 17, 10543403: 10543405
11 MYH3 NM_002470.3(MYH3): c.1123G> A (p.Glu375Lys) single nucleotide variant Pathogenic rs121913621 GRCh37 Chromosome 17, 10549042: 10549042
12 MYH3 NM_002470.3(MYH3): c.1385A> G (p.Asp462Gly) single nucleotide variant Pathogenic rs121913622 GRCh37 Chromosome 17, 10547693: 10547693
13 MYH3 NM_002470.3(MYH3): c.700G> A (p.Ala234Thr) single nucleotide variant Pathogenic/Likely pathogenic rs121913623 GRCh37 Chromosome 17, 10551909: 10551909
14 TNNI2 NM_003282.3(TNNI2): c.525G> T (p.Lys175Asn) single nucleotide variant Likely pathogenic rs797046046 GRCh38 Chromosome 11, 1841527: 1841527
15 MYH3 NM_002470.3(MYH3): c.850T> G (p.Tyr284Asp) single nucleotide variant Likely pathogenic rs886042111 GRCh37 Chromosome 17, 10550547: 10550547

Expression for Arthrogryposis, Distal, Type 2b

Search GEO for disease gene expression data for Arthrogryposis, Distal, Type 2b.

Pathways for Arthrogryposis, Distal, Type 2b

GO Terms for Arthrogryposis, Distal, Type 2b

Cellular components related to Arthrogryposis, Distal, Type 2b according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 troponin complex GO:0005861 8.62 TNNI2 TNNT3

Biological processes related to Arthrogryposis, Distal, Type 2b according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 regulation of muscle contraction GO:0006937 9.26 TNNI2 TNNT3
2 regulation of ATPase activity GO:0043462 9.16 TNNT3 TPM2
3 skeletal muscle contraction GO:0003009 9.13 MYH3 TNNI2 TNNT3
4 muscle filament sliding GO:0030049 8.92 MYH3 TNNI2 TNNT3 TPM2

Molecular functions related to Arthrogryposis, Distal, Type 2b according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 actin filament binding GO:0051015 8.96 MYH3 TPM2
2 actin binding GO:0003779 8.92 MYH3 TNNI2 TNNT3 TPM2

Sources for Arthrogryposis, Distal, Type 2b

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
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