DA2B
MCID: ART155
MIFTS: 47

Arthrogryposis, Distal, Type 2b1 (DA2B)

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

Aliases & Classifications for Arthrogryposis, Distal, Type 2b1

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

Name: Arthrogryposis, Distal, Type 2b1 58
Distal Arthrogryposis Type 2b 54 26 60 30 6
Sheldon-Hall Syndrome 58 54 26 60 76
Freeman-Sheldon Syndrome Variant 58 54 60 76
Arthrogryposis Multiplex Congenita, Distal, Type 2b 58 26 13
Da2b 54 26 76
Shs 58 26 76
Arthrogryposis Multiplex Congenita Distal Type Ii with Craniofacial Abnormalities 54 76
Arthrogryposis Multiplex Congenita Distal Type 2b 54 76
Fssv 58 76
Arthrogryposis Multiplex Congenita, Distal, Type Ii, with Craniofacial Abnormalities 58
Freeman-Sheldon Syndrome Variant; Fssv 58
Freeman Sheldon Syndrome, Variant 54
Arthrogryposis, Distal, Type 2b 41
Distal Arthrogryposis Type Iib 54
Sheldon-Hall Syndrome; Shs 58
Arthrogryposis, Distal, 2b 76
Freeman Sheldon Variant 54
Amcd2b 76
Da2b1 58

Characteristics:

Orphanet epidemiological data:

60
sheldon-hall syndrome
Inheritance: Autosomal dominant,Not applicable; Age of onset: Neonatal; Age of death: normal life expectancy;

OMIM:

58
Inheritance:
autosomal dominant


HPO:

33
arthrogryposis, distal, type 2b1:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Arthrogryposis, Distal, Type 2b1

OMIM : 58 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 2b1, also known as distal arthrogryposis type 2b, is related to arthrogryposis, distal, type 5 and distal arthrogryposis, 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. Affiliated tissues include skin, bone and kidney, and related phenotypes are scoliosis and joint stiffness

Genetics Home Reference : 26 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.

NIH Rare Diseases : 54 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.   

UniProtKB/Swiss-Prot : 76 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 9 Arthrogryposis, Distal, Type 2e
Arthrogryposis, Distal, Type 7 Arthrogryposis, Distal, Type 8
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 118)
# Related Disease Score Top Affiliating Genes
1 arthrogryposis, distal, type 5 31.2 MYH3 NALCN TNNI2 TNNT3 TPM2
2 distal arthrogryposis 30.9 MYH3 NALCN TNNI2 TNNT3 TPM2
3 arthrogryposis, distal, type 2a 30.1 MYH3 NALCN
4 congenital contractures 29.7 NALCN TNNT3
5 renpenning syndrome 1 11.4
6 arthrogryposis, distal, type 1a 11.3
7 neuroblastoma 1 10.6
8 mumps 10.4
9 glyceraldehyde-3-phosphate dehydrogenase deficiency 10.3
10 salla disease 10.2
11 hepatitis 10.2
12 dysentery 10.2
13 australia antigen 10.1
14 cystic fibrosis 10.0
15 immunodysregulation, polyendocrinopathy, and enteropathy, x-linked 10.0
16 liver disease 10.0
17 neuropathy 10.0
18 hemorrhoid 10.0
19 allergic encephalomyelitis 10.0
20 hepatocellular carcinoma 9.9
21 polykaryocytosis inducer 9.9
22 cryohydrocytosis 9.9
23 ocular motor apraxia 9.9
24 noonan syndrome 2 9.9
25 pulmonary hypertension, primary, 3 9.9
26 autoimmune lymphoproliferative syndrome, type v 9.9
27 helix syndrome 9.9
28 cataract 9.9
29 bacterial infectious disease 9.9
30 hepatic coma 9.9
31 senile cataract 9.9
32 polyarteritis nodosa 9.9
33 rere-related disorders 9.9
34 alzheimer disease 9.7
35 leukemia, chronic lymphocytic 2 9.7
36 blood group, colton system 9.7
37 breast cancer 9.7
38 leukemia, chronic lymphocytic 9.7
39 pheochromocytoma 9.7
40 rheumatoid arthritis 9.7
41 ataxia-telangiectasia 9.7
42 disorganization, mouse, homolog of 9.7
43 myasthenia gravis 9.7
44 neutrophil actin dysfunction 9.7
45 asthma 9.7
46 horns in sheep 9.7
47 spondyloocular syndrome 9.7
48 hepatitis c virus 9.7
49 west nile virus 9.7
50 deafness-infertility syndrome 9.7

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:

60 33 (show all 36)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 scoliosis 60 33 hallmark (90%) Very frequent (99-80%) HP:0002650
2 joint stiffness 60 33 hallmark (90%) Very frequent (99-80%) HP:0001387
3 webbed neck 60 33 hallmark (90%) Very frequent (99-80%) HP:0000465
4 bilateral single transverse palmar creases 60 33 hallmark (90%) Very frequent (99-80%) HP:0007598
5 adducted thumb 60 33 hallmark (90%) Very frequent (99-80%) HP:0001181
6 aplasia/hypoplasia of the radius 60 33 hallmark (90%) Very frequent (99-80%) HP:0006501
7 short neck 60 33 frequent (33%) Frequent (79-30%) HP:0000470
8 high palate 60 33 frequent (33%) Frequent (79-30%) HP:0000218
9 wide nasal bridge 60 33 frequent (33%) Frequent (79-30%) HP:0000431
10 short stature 60 33 frequent (33%) Frequent (79-30%) HP:0004322
11 micrognathia 60 33 frequent (33%) Frequent (79-30%) HP:0000347
12 abnormality of the hip bone 60 33 frequent (33%) Frequent (79-30%) HP:0003272
13 protruding ear 60 33 frequent (33%) Frequent (79-30%) HP:0000411
14 narrow face 60 33 frequent (33%) Frequent (79-30%) HP:0000275
15 round ear 60 33 frequent (33%) Frequent (79-30%) HP:0100830
16 vertebral segmentation defect 60 33 frequent (33%) Frequent (79-30%) HP:0003422
17 ulnar deviation of finger 60 33 frequent (33%) Frequent (79-30%) HP:0009465
18 tarsal synostosis 60 33 frequent (33%) Frequent (79-30%) HP:0008368
19 overlapping fingers 60 33 frequent (33%) Frequent (79-30%) HP:0010557
20 ulnar deviation of the wrist 60 33 frequent (33%) Frequent (79-30%) HP:0003049
21 mandibular prognathia 33 HP:0000303
22 long philtrum 33 HP:0000343
23 metatarsus adductus 33 HP:0001840
24 arthrogryposis multiplex congenita 33 HP:0002804
25 talipes equinovarus 33 HP:0001762
26 downslanted palpebral fissures 33 HP:0000494
27 narrow mouth 33 HP:0000160
28 triangular face 33 HP:0000325
29 camptodactyly of finger 33 HP:0100490
30 rocker bottom foot 33 HP:0001838
31 abnormality of the ear 33 HP:0000598
32 ulnar deviation of the hand or of fingers of the hand 33 HP:0001193
33 calcaneovalgus deformity 33 HP:0001848
34 prominent nasolabial fold 33 HP:0005272
35 distal arthrogryposis 33 HP:0005684
36 absent phalangeal crease 33 HP:0006109

Symptoms via clinical synopsis from OMIM:

58
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

Interventional clinical trials:


# 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 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 30 MYH3 TNNI2 TNNT3 TPM2

Anatomical Context for Arthrogryposis, Distal, Type 2b1

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

42
Skin, Bone, Kidney, Liver, Breast, Brain, Eye

Publications for Arthrogryposis, Distal, Type 2b1

Articles related to Arthrogryposis, Distal, Type 2b1:

(show all 12)
# Title Authors Year
1
Intrafamilial variability of clinical features in distal arthrogryposis type 2B. ( 30216196 )
2019
2
7 Mb de novo deletion within 8q21 in a patient with distal arthrogryposis type 2B (DA2B). ( 21722758 )
2011
3
Skeletal muscle contractile gene (TNNT3, MYH3, TPM2) mutations not found in vertical talus or clubfoot. ( 19142688 )
2009
4
Embryonic myosin heavy-chain mutations cause distal arthrogryposis and developmental myosin myopathy that persists postnatally. ( 18695058 )
2008
5
Distal arthrogryposis and muscle weakness associated with a beta-tropomyosin mutation. ( 17339586 )
2007
6
Molecular prenatal diagnosis for hereditary distal arthrogryposis type 2B. ( 17380469 )
2007
7
A TNNI2 mutation in a family with distal arthrogryposis type 2B. ( 16497570 )
2006
8
Recurrence of the p.R156X TNNI2 mutation in distal arthrogryposis type 2B. ( 17101001 )
2006
9
Mutations in embryonic myosin heavy chain (MYH3) cause Freeman-Sheldon syndrome and Sheldon-Hall syndrome. ( 16642020 )
2006
10
Mutations in TNNT3 cause multiple congenital contractures: a second locus for distal arthrogryposis type 2B. ( 12865991 )
2003
11
Mutations in genes encoding fast-twitch contractile proteins cause distal arthrogryposis syndromes. ( 12592607 )
2003
12
A new mutation of the cardiac troponin T gene causing familial hypertrophic cardiomyopathy without left ventricular hypertrophy. ( 10525521 )
1999

Variations for Arthrogryposis, Distal, Type 2b1

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

76
# 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 2b1:

6 (show all 22)
# Gene Variation Type Significance SNP ID Assembly Location
1 TNNI2 NM_003282.3(TNNI2): c.521G> A (p.Arg174Gln) single nucleotide variant Pathogenic rs104894311 GRCh37 Chromosome 11, 1862753: 1862753
2 TNNI2 NM_003282.3(TNNI2): c.521G> A (p.Arg174Gln) single nucleotide variant Pathogenic rs104894311 GRCh38 Chromosome 11, 1841523: 1841523
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.466C> T (p.Arg156Ter) single nucleotide variant Pathogenic rs104894312 GRCh38 Chromosome 11, 1841468: 1841468
5 TNNI2 NM_003282.3(TNNI2): c.499_501delGAG (p.Glu167del) deletion Pathogenic rs199474800 GRCh37 Chromosome 11, 1862731: 1862733
6 TNNI2 NM_003282.3(TNNI2): c.499_501delGAG (p.Glu167del) deletion Pathogenic rs199474800 GRCh38 Chromosome 11, 1841501: 1841503
7 MYH3 NM_002470.3(MYH3): c.700G> A (p.Ala234Thr) single nucleotide variant Likely pathogenic rs121913623 GRCh37 Chromosome 17, 10551909: 10551909
8 MYH3 NM_002470.3(MYH3): c.700G> A (p.Ala234Thr) single nucleotide variant Likely pathogenic rs121913623 GRCh38 Chromosome 17, 10648592: 10648592
9 TNNT3 NM_006757.3(TNNT3): c.762C> T (p.Gly254=) single nucleotide variant Benign/Likely benign rs4727 GRCh37 Chromosome 11, 1959707: 1959707
10 TNNT3 NM_006757.3(TNNT3): c.762C> T (p.Gly254=) single nucleotide variant Benign/Likely benign rs4727 GRCh38 Chromosome 11, 1938477: 1938477
11 TNNI2 NM_003282.3(TNNI2): c.60T> C (p.Ser20=) single nucleotide variant Benign/Likely benign rs907610 GRCh37 Chromosome 11, 1861760: 1861760
12 TNNI2 NM_003282.3(TNNI2): c.60T> C (p.Ser20=) single nucleotide variant Benign/Likely benign rs907610 GRCh38 Chromosome 11, 1840530: 1840530
13 TNNI2 NM_003282.3(TNNI2): c.525G> T (p.Lys175Asn) single nucleotide variant Likely pathogenic rs797046046 GRCh37 Chromosome 11, 1862757: 1862757
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
16 MYH3 NM_002470.3(MYH3): c.850T> G (p.Tyr284Asp) single nucleotide variant Likely pathogenic rs886042111 GRCh38 Chromosome 17, 10647230: 10647230
17 MYH3 NM_002470.3(MYH3): c.4826G> A (p.Arg1609Lys) single nucleotide variant Likely pathogenic rs1555525264 GRCh37 Chromosome 17, 10535923: 10535923
18 MYH3 NM_002470.3(MYH3): c.4826G> A (p.Arg1609Lys) single nucleotide variant Likely pathogenic rs1555525264 GRCh38 Chromosome 17, 10632606: 10632606
19 TPM2 NM_213674.1(TPM2): c.826C> G (p.Gln276Glu) single nucleotide variant Uncertain significance rs376668943 GRCh38 Chromosome 9, 35682110: 35682110
20 TPM2 NM_213674.1(TPM2): c.826C> G (p.Gln276Glu) single nucleotide variant Uncertain significance rs376668943 GRCh37 Chromosome 9, 35682107: 35682107
21 MYH3 NM_002470.3(MYH3): c.4129G> C (p.Glu1377Gln) single nucleotide variant Uncertain significance GRCh37 Chromosome 17, 10538727: 10538727
22 MYH3 NM_002470.3(MYH3): c.4129G> C (p.Glu1377Gln) single nucleotide variant Uncertain significance GRCh38 Chromosome 17, 10635410: 10635410

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 TNNI2 TNNT3

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 TNNI2 TNNT3
2 sarcomere organization GO:0045214 9.37 MYH3 TNNT3
3 muscle contraction GO:0006936 9.33 TNNI2 TNNT3 TPM2
4 regulation of muscle contraction GO:0006937 9.32 TNNI2 TNNT3
5 regulation of ATPase activity GO:0043462 9.26 TNNT3 TPM2
6 skeletal muscle contraction GO:0003009 9.13 MYH3 TNNI2 TNNT3
7 muscle filament sliding GO:0030049 8.92 MYH3 TNNI2 TNNT3 TPM2

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 MYH3 TPM2
2 actin binding GO:0003779 8.92 MYH3 TNNI2 TNNT3 TPM2

Sources for Arthrogryposis, Distal, Type 2b1

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7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
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43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
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55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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