DA2B1
MCID: ART155
MIFTS: 47

Arthrogryposis, Distal, Type 2b1 (DA2B1)

Categories: Bone diseases, Ear diseases, Eye diseases, Fetal diseases, Genetic diseases, Muscle diseases, Neuronal diseases, Oral diseases, Rare diseases, Respiratory diseases, Skin diseases, Smell/Taste diseases

Aliases & Classifications for Arthrogryposis, Distal, Type 2b1

MalaCards integrated aliases for Arthrogryposis, Distal, Type 2b1:

Name: Arthrogryposis, Distal, Type 2b1 57
Distal Arthrogryposis Type 2b 53 25 59 29 6
Sheldon-Hall Syndrome 57 53 25 59 74
Freeman-Sheldon Syndrome Variant 57 53 59 74
Arthrogryposis Multiplex Congenita, Distal, Type 2b 57 25 13
Da2b 53 25 74
Shs 57 25 74
Arthrogryposis Multiplex Congenita Distal Type Ii with Craniofacial Abnormalities 53 74
Arthrogryposis Multiplex Congenita Distal Type 2b 53 74
Fssv 57 74
Arthrogryposis Multiplex Congenita, Distal, Type Ii, with Craniofacial Abnormalities 57
Freeman-Sheldon Syndrome Variant; Fssv 57
Freeman Sheldon Syndrome, Variant 53
Distal Arthrogryposis Type Iib 53
Sheldon-Hall Syndrome; Shs 57
Arthrogryposis, Distal, 2b 74
Freeman Sheldon Variant 53
Amcd2b 74
Da2b1 57

Characteristics:

Orphanet epidemiological data:

59
sheldon-hall syndrome
Inheritance: Autosomal dominant,Not applicable; Age of onset: Neonatal; Age of death: normal life expectancy;

OMIM:

57
Inheritance:
autosomal dominant


HPO:

32
arthrogryposis, distal, type 2b1:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

MeSH 44 D001176
ICD10 via Orphanet 34 Q68.8
UMLS via Orphanet 73 C1834523
Orphanet 59 ORPHA1147
MedGen 42 C1834523

Summaries for Arthrogryposis, Distal, Type 2b1

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. People with Sheldon-Hall syndrome also usually have distinctive facial features, which include a triangular face; outside corners of the eyes that point downward (down-slanting palpebral fissures); deep folds in the skin between the nose and lips (nasolabial folds); and a small mouth with a high, arched roof of the mouth (palate). Other features that may occur in Sheldon-Hall syndrome include extra folds of skin on the neck (webbed neck) and short stature. Sheldon-Hall syndrome does not usually affect other parts of the body, and intelligence and life expectancy are normal in this disorder.

MalaCards based summary : Arthrogryposis, Distal, Type 2b1, also known as distal arthrogryposis type 2b, is related to distal arthrogryposis and arthrogryposis, distal, type 5, and has symptoms including ulnar deviation of the wrist An important gene associated with Arthrogryposis, Distal, Type 2b1 is TNNI2 (Troponin I2, Fast Skeletal Type), and among its related pathways/superpathways are Cardiac conduction and Striated Muscle Contraction. The drugs Adenosine and Analgesics have been mentioned in the context of this disorder. Affiliated tissues include skin, eye and bone, and related phenotypes are scoliosis and joint stiffness

NIH Rare Diseases : 53 Sheldon-Hall syndrome, also known as distal arthrogryposis type 2B, is characterized by joint deformities (contractures) that restrict movement in the hands and feet. People with this condition may also have distinctive facial features, extra folds of skin on the neck, and short stature. Intelligence and life expectancy are not usually affected. Sheldon-Hall syndrome can be caused by mutations in the MYH3, TNNI2, TNNT3, or TPM2 gene. It is inherited in an autosomal dominant pattern. In about 50% of cases, an affected person inherits the mutation from an affected parent. Other cases result from a new mutation in the gene and occur in people with no family history of the disorder. While there is no specific treatment for this condition, occupational and physical therapy, serial casting, and/or surgery may benefit those who are affected.

OMIM : 57 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)

UniProtKB/Swiss-Prot : 74 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 2b1

Diseases in the Distal Arthrogryposis family:

Arthrogryposis, Distal, Type 1a Arthrogryposis, Distal, Type 5
Arthrogryposis, Distal, Type 6 Arthrogryposis, Distal, Type 3
Arthrogryposis, Distal, Type 2e Arthrogryposis, Distal, Type 7
Arthrogryposis, Distal, Type 10 Arthrogryposis, Distal, Type 2a
Arthrogryposis, Distal, Type 2b1 Arthrogryposis, Distal, Type 4
Arthrogryposis, Distal, Type 1b Arthrogryposis, Distal, Type 5d
Arthrogryposis, Distal, Type 2b2 Arthrogryposis, Distal, Type 2b3

Diseases related to Arthrogryposis, Distal, Type 2b1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 289)
# Related Disease Score Top Affiliating Genes
1 distal arthrogryposis 30.8 TPM2 TNNT3 TNNI2 NALCN MYH3
2 arthrogryposis, distal, type 5 30.4 TPM2 TNNT3 TNNI2 NALCN MYH3
3 arthrogryposis, distal, type 2a 30.3 NALCN MYH3
4 congenital contractures 30.3 TNNT3 NALCN
5 clubfoot 28.8 TPM2 TNNT3 MYH3
6 muscular disease 27.5 TPM2 TNNT3 TNNI2 MYH3
7 arthrogryposis, distal, type 1a 11.9
8 renpenning syndrome 1 11.5
9 neuroblastoma 1 10.9
10 alkuraya-kucinskas syndrome 10.7
11 congenital amyoplasia 10.7
12 dysentery 10.4
13 arthrogryposis, distal, type 2b3 10.4
14 mumps 10.4
15 hepatitis 10.4
16 viral hepatitis 10.3
17 australia antigen 10.3
18 liver disease 10.3
19 pertussis 10.3
20 kearns-sayre syndrome 10.3
21 ptosis 10.3
22 clubfoot, congenital, with or without deficiency of long bones and/or mirror-image polydactyly 10.2
23 contractures, pterygia, and variable skeletal fusions syndrome 1a 10.2
24 arthrogryposis, distal, type 2b2 10.2
25 scoliosis 10.2
26 synostosis 10.2
27 oligohydramnios 10.2
28 myopathy 10.2
29 talipes equinovarus 10.2
30 vaccinia 10.2
31 b-cell lymphoma 10.2
32 hypotrichosis and recurrent skin vesicles 10.2
33 epicanthus 10.2
34 triiodothyronine receptor auxiliary protein 10.1
35 prostatic hypertrophy 10.1
36 allergic hypersensitivity disease 10.1
37 hemangioma 10.1
38 strabismus 10.1
39 astigmatism 10.1
40 keratoconus 10.1
41 mechanical strabismus 10.1
42 alzheimer disease 10.1
43 lymphoma 10.1
44 pheochromocytoma 10.0
45 pulmonary hypertension, primary, 3 10.0
46 adrenal gland pheochromocytoma 10.0
47 neutropenia 10.0
48 insulin-like growth factor i 10.0
49 helix syndrome 10.0
50 cholera 10.0

Graphical network of the top 20 diseases related to Arthrogryposis, Distal, Type 2b1:



Diseases related to Arthrogryposis, Distal, Type 2b1

Symptoms & Phenotypes for Arthrogryposis, Distal, Type 2b1

Human phenotypes related to Arthrogryposis, Distal, Type 2b1:

59 32 (show all 36)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 scoliosis 59 32 hallmark (90%) Very frequent (99-80%) HP:0002650
2 joint stiffness 59 32 hallmark (90%) Very frequent (99-80%) HP:0001387
3 webbed neck 59 32 hallmark (90%) Very frequent (99-80%) HP:0000465
4 bilateral single transverse palmar creases 59 32 hallmark (90%) Very frequent (99-80%) HP:0007598
5 adducted thumb 59 32 hallmark (90%) Very frequent (99-80%) HP:0001181
6 aplasia/hypoplasia of the radius 59 32 hallmark (90%) Very frequent (99-80%) HP:0006501
7 short neck 59 32 frequent (33%) Frequent (79-30%) HP:0000470
8 high palate 59 32 frequent (33%) Frequent (79-30%) HP:0000218
9 wide nasal bridge 59 32 frequent (33%) Frequent (79-30%) HP:0000431
10 short stature 59 32 frequent (33%) Frequent (79-30%) HP:0004322
11 micrognathia 59 32 frequent (33%) Frequent (79-30%) HP:0000347
12 protruding ear 59 32 frequent (33%) Frequent (79-30%) HP:0000411
13 abnormality of the hip bone 59 32 frequent (33%) Frequent (79-30%) HP:0003272
14 narrow face 59 32 frequent (33%) Frequent (79-30%) HP:0000275
15 round ear 59 32 frequent (33%) Frequent (79-30%) HP:0100830
16 vertebral segmentation defect 59 32 frequent (33%) Frequent (79-30%) HP:0003422
17 ulnar deviation of finger 59 32 frequent (33%) Frequent (79-30%) HP:0009465
18 tarsal synostosis 59 32 frequent (33%) Frequent (79-30%) HP:0008368
19 overlapping fingers 59 32 frequent (33%) Frequent (79-30%) HP:0010557
20 ulnar deviation of the wrist 59 32 frequent (33%) Frequent (79-30%) HP:0003049
21 mandibular prognathia 32 HP:0000303
22 long philtrum 32 HP:0000343
23 narrow mouth 32 HP:0000160
24 metatarsus adductus 32 HP:0001840
25 arthrogryposis multiplex congenita 32 HP:0002804
26 talipes equinovarus 32 HP:0001762
27 downslanted palpebral fissures 32 HP:0000494
28 triangular face 32 HP:0000325
29 camptodactyly of finger 32 HP:0100490
30 rocker bottom foot 32 HP:0001838
31 abnormality of the ear 32 HP:0000598
32 distal arthrogryposis 32 HP:0005684
33 ulnar deviation of the hand or of fingers of the hand 32 HP:0001193
34 calcaneovalgus deformity 32 HP:0001848
35 prominent nasolabial fold 32 HP:0005272
36 absent phalangeal crease 32 HP:0006109

Symptoms via clinical synopsis from OMIM:

57
Growth Height:
short stature

Head And Neck Neck:
webbed neck

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

Head And Neck Mouth:
high-arched palate
small mouth

Skeletal:
joint contractures
precocious arthrosis

Head And Neck Ears:
attached ear lobules

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

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

Head And Neck Eyes:
downslanting palpebral fissures

Skeletal Hands:
ulnar deviation
severe camptodactyly
overriding fingers (neonate)
thumb adduction
contractures of the proximal interphalangeal (pip) joints
more
Skeletal Spine:
scoliosis (less common)

Skeletal Limbs:
ulnar wrist deviation

Clinical features from OMIM:

601680

UMLS symptoms related to Arthrogryposis, Distal, Type 2b1:


ulnar deviation of the wrist

Drugs & Therapeutics for Arthrogryposis, Distal, Type 2b1

Drugs for Arthrogryposis, Distal, Type 2b1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 7)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Adenosine Approved, Investigational 58-61-7 60961
2 Analgesics
3 Neurotransmitter Agents
4 Peripheral Nervous System Agents
5 Purinergic P1 Receptor Agonists
6 Anti-Arrhythmia Agents
7 Vasodilator Agents

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Study of Therapeutic Outcomes and Practices in Freeman-Sheldon Syndrome Recruiting NCT01144741
2 Freeman-Sheldon Syndrome Evaluation and Diagnosis in Clinical Settings (FSS-EDICT) I: a Case-Control, Cross-Sectional Study of Baseline and Stress Physiology Parameters Not yet recruiting NCT01306994

Search NIH Clinical Center for Arthrogryposis, Distal, Type 2b1

Genetic Tests for Arthrogryposis, Distal, Type 2b1

Genetic tests related to Arthrogryposis, Distal, Type 2b1:

# Genetic test Affiliating Genes
1 Distal Arthrogryposis Type 2b 29 TNNI2

Anatomical Context for Arthrogryposis, Distal, Type 2b1

MalaCards organs/tissues related to Arthrogryposis, Distal, Type 2b1:

41
Skin, Eye, Bone, Skeletal Muscle

Publications for Arthrogryposis, Distal, Type 2b1

Articles related to Arthrogryposis, Distal, Type 2b1:

(show all 30)
# Title Authors PMID Year
1
A TNNI2 mutation in a family with distal arthrogryposis type 2B. 8 71
16497570 2006
2
Mutations in genes encoding fast-twitch contractile proteins cause distal arthrogryposis syndromes. 8 71
12592607 2003
3
Arthrogryposis: a review and update. 8
19571066 2009
4
Mutations in fast skeletal troponin I, troponin T, and beta-tropomyosin that cause distal arthrogryposis all increase contractile function. 8
17194691 2007
5
Recurrence of the p.R156X TNNI2 mutation in distal arthrogryposis type 2B. 71
17101001 2006
6
A novel deletion in TNNI2 causes distal arthrogryposis in a large Chinese family with marked variability of expression. 8
16802141 2006
7
A mutation in the fast skeletal muscle troponin I gene causes myopathy and distal arthrogryposis. 8
16924011 2006
8
Clinical analysis of a variant of Freeman-Sheldon syndrome (DA2B). 8
9508073 1998
9
A variant of Freeman-Sheldon syndrome maps to 11p15.5-pter. 8
9012416 1997
10
A revised and extended classification of the distal arthrogryposes. 8
8923935 1996
11
Dominant distal arthrogryposis in a Maori family with marked variability of expression. 8
7762579 1995
12
Familial distal arthrogryposis with craniofacial abnormalities: a new subtype of type II? 8
2764034 1989
13
Distal arthrogryposis type II: a family with varying congenital abnormalities. 8
3717209 1986
14
An unusual distal arthrogryposis. 8
3993671 1985
15
The distal arthrogryposes: delineation of new entities--review and nosologic discussion. 8
7039311 1982
16
Cranio-carpo-tarsal dystrophy. 8
21032118 1938
17
Myosin heavy chain mutations that cause Freeman-Sheldon syndrome lead to muscle structural and functional defects in Drosophila. 38
30826400 2019
18
A MYH3 mutation identified for the first time in a Chinese family with Sheldon-Hall syndrome (DA2B). 38
29625835 2018
19
A novel pathogenic MYH3 mutation in a child with Sheldon-Hall syndrome and vertebral fusions. 38
29314551 2018
20
The clubfoot painted by Jusepe de Ribera: a controversial diagnosis. 38
26414783 2016
21
Freeman-Sheldon syndrome in a 29-year-old woman presenting with rare and previously undescribed features. 38
26494722 2015
22
Anesthetic considerations in Sheldon-Hall syndrome. 38
24829975 2014
23
First Korean family with a mutation in TPM2 associated with Sheldon-Hall syndrome. 38
23678273 2013
24
Exome sequencing identifies an MYH3 mutation in a family with distal arthrogryposis type 1. 38
21531865 2011
25
A novel mutation in TNNT3 associated with Sheldon-Hall syndrome in a Chinese family with vertical talus. 38
21402185 2011
26
Prenatal diagnosis of Sheldon Hall syndrome. 38
19488977 2009
27
Skeletal muscle contractile gene (TNNT3, MYH3, TPM2) mutations not found in vertical talus or clubfoot. 38
19142688 2009
28
Sheldon-Hall syndrome. 38
19309503 2009
29
Distal arthrogryposis syndrome. 38
20300297 2008
30
Mutations in embryonic myosin heavy chain (MYH3) cause Freeman-Sheldon syndrome and Sheldon-Hall syndrome. 38
16642020 2006

Variations for Arthrogryposis, Distal, Type 2b1

ClinVar genetic disease variations for Arthrogryposis, Distal, Type 2b1:

6
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 TNNI2 NM_003282.4(TNNI2): c.521G> A (p.Arg174Gln) single nucleotide variant Pathogenic rs104894311 11:1862753-1862753 11:1841523-1841523
2 TNNI2 NM_003282.4(TNNI2): c.466C> T (p.Arg156Ter) single nucleotide variant Pathogenic rs104894312 11:1862698-1862698 11:1841468-1841468
3 TNNI2 NM_003282.4(TNNI2): c.496_498GAG[1] (p.Glu167del) short repeat Pathogenic rs199474800 11:1862731-1862733 11:1841501-1841503
4 MYH3 NM_002470.4(MYH3): c.700G> A (p.Ala234Thr) single nucleotide variant Likely pathogenic rs121913623 17:10551909-10551909 17:10648592-10648592
5 MYH3 NM_002470.4(MYH3): c.4826G> A (p.Arg1609Lys) single nucleotide variant Likely pathogenic rs1555525264 17:10535923-10535923 17:10632606-10632606
6 TNNI2 NM_003282.4(TNNI2): c.525G> T (p.Lys175Asn) single nucleotide variant Likely pathogenic rs797046046 11:1862757-1862757 11:1841527-1841527
7 MYH3 NM_002470.4(MYH3): c.4129G> C (p.Glu1377Gln) single nucleotide variant Uncertain significance 17:10538727-10538727 17:10635410-10635410
8 TPM2 NM_213674.1(TPM2): c.826C> G (p.Gln276Glu) single nucleotide variant Uncertain significance rs376668943 9:35682107-35682107 9:35682110-35682110
9 TNNT3 NM_006757.4(TNNT3): c.762C> T (p.Gly254=) single nucleotide variant Benign/Likely benign rs4727 11:1959707-1959707 11:1938477-1938477
10 TNNI2 NM_003282.4(TNNI2): c.60T> C (p.Ser20=) single nucleotide variant Benign/Likely benign rs907610 11:1861760-1861760 11:1840530-1840530

UniProtKB/Swiss-Prot genetic disease variations for Arthrogryposis, Distal, Type 2b1:

74
# 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

Expression for Arthrogryposis, Distal, Type 2b1

Search GEO for disease gene expression data for Arthrogryposis, Distal, Type 2b1.

Pathways for Arthrogryposis, Distal, Type 2b1

GO Terms for Arthrogryposis, Distal, Type 2b1

Cellular components related to Arthrogryposis, Distal, Type 2b1 according to GeneCards Suite gene sharing:

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

Biological processes related to Arthrogryposis, Distal, Type 2b1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cardiac muscle contraction GO:0060048 9.4 TNNT3 TNNI2
2 sarcomere organization GO:0045214 9.37 TNNT3 MYH3
3 muscle contraction GO:0006936 9.33 TPM2 TNNT3 TNNI2
4 regulation of muscle contraction GO:0006937 9.32 TNNT3 TNNI2
5 regulation of ATPase activity GO:0043462 9.26 TPM2 TNNT3
6 skeletal muscle contraction GO:0003009 9.13 TNNT3 TNNI2 MYH3
7 muscle filament sliding GO:0030049 8.92 TPM2 TNNT3 TNNI2 MYH3

Molecular functions related to Arthrogryposis, Distal, Type 2b1 according to GeneCards Suite gene sharing:

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

Sources for Arthrogryposis, Distal, Type 2b1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 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
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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