DA5
MCID: ART119
MIFTS: 43

Arthrogryposis, Distal, Type 5 (DA5)

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 5

MalaCards integrated aliases for Arthrogryposis, Distal, Type 5:

Name: Arthrogryposis, Distal, Type 5 56 39
Oculomelic Amyoplasia 56 12 74 52 58 73 29 6 43 71
Distal Arthrogryposis Type Iib 12 52 58 73
Distal Arthrogryposis Type 2b 12 29 6 43
Arthrogryposis with Oculomotor Limitation and Electroretinal Abnormalities 56 52 73
Arthrogryposis-Oculomotor Limitation-Electroretinal Anomalies Syndrome 12 52 58
Distal Arthrogryposis with Ophthalmoplegia 12 52 58
Distal Arthrogryposis Type 5 12 52 58
Daiib 56 12 73
Da5 56 12 73
Arthrogryposis, Distal, Type 2b 39 71
Arthogryposis with Oculomotor Limitation and Electroretinal Abnormalities 52
Arthrogryposis- Oculomotor Limitation-Electroretinal Anomalies Syndrome 52
Arthrogryposis Ophthalmoplegia Retinopathy 52
Arthrogryposis, Distal, Type Iib; Daiib 56
Arthrogryposis, Distal, Type Iib 56
Freeman-Sheldon Syndrome Variant 12
Arthrogryposis, Distal, 5 73
Sheldon-Hall Syndrome 12
Da2b 12

Characteristics:

Orphanet epidemiological data:

58
arthrogryposis-oculomotor limitation-electroretinal anomalies syndrome
Inheritance: Autosomal dominant,Autosomal recessive; Age of onset: Neonatal; Age of death: normal life expectancy;

OMIM:

56
Inheritance:
autosomal dominant


HPO:

31
arthrogryposis, distal, type 5:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Developmental anomalies during embryogenesis


Summaries for Arthrogryposis, Distal, Type 5

OMIM : 56 Distal arthrogryposis type 5 is distinguished from other forms of DA by the presence of ocular abnormalities, typically ptosis, ophthalmoplegia, and/or strabismus, in addition to contractures of the skeletal muscles. Some cases have been reported to have pulmonary hypertension as a result of restrictive lung disease (summary by Bamshad et al., 2009). There are 2 syndromes with features overlapping those of DA5 that are also caused by heterozygous mutation in PIEZO2: distal arthrogryposis type 3 (DA3, or Gordon syndrome; 114300) and Marden-Walker syndrome (MWKS; 248700), which are distinguished by the presence of cleft palate and mental retardation, respectively. McMillin et al. (2014) suggested that the 3 disorders might represent variable expressivity of the same condition. For a general phenotypic description and a discussion of genetic heterogeneity of distal arthrogryposis, see DA1A (108120). (108145)

MalaCards based summary : Arthrogryposis, Distal, Type 5, also known as oculomelic amyoplasia, is related to distal arthrogryposis and arthrogryposis, distal, type 2b1, and has symptoms including ophthalmoplegia and ulnar deviation of the wrist. An important gene associated with Arthrogryposis, Distal, Type 5 is PIEZO2 (Piezo Type Mechanosensitive Ion Channel Component 2). The drugs Adenosine and Analgesics have been mentioned in the context of this disorder. Affiliated tissues include lung, skeletal muscle and eye, and related phenotypes are pectus excavatum and ptosis

Disease Ontology : 12 A distal arthrogryposis characterized by distal arthrogryposis with ocular abnormalities that has material basis in heterozygous gain of function mutation in PIEZO2 on chromosome 18p11.22-p11.21.

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 1154 Definition Distal arthrogryposis type 5 is an inherited developmental defect syndrome characterized by multiple congenital contractures of limbs, without primary neurologic and/or muscle disease that affects limb function, and ocular anomalies (ptosis , external ophtalmoplegia and/or strabismus ). Intelligence is normal. Visit the Orphanet disease page for more resources.

UniProtKB/Swiss-Prot : 73 Arthrogryposis, distal, 5: 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. DA5 features include ocular abnormalities, typically ptosis, ophthalmoplegia and/or strabismus, in addition to contractures of the skeletal muscles. Some patients have pulmonary hypertension as a result of restrictive lung disease.

Wikipedia : 74 Arthrogryposis multiplex congenita (AMC), or simply arthrogryposis, describes congenital joint... more...

Related Diseases for Arthrogryposis, Distal, Type 5

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 5 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 31)
# Related Disease Score Top Affiliating Genes
1 distal arthrogryposis 32.4 TNNI2 PIEZO2
2 arthrogryposis, distal, type 2b1 12.8
3 arthrogryposis, distal, type 1a 11.9
4 arthrogryposis, distal, type 3 11.2
5 marden-walker syndrome 11.2
6 arthrogryposis, distal, type 5d 11.2
7 alkuraya-kucinskas syndrome 10.7
8 congenital amyoplasia 10.7
9 arthrogryposis, distal, type 2a 10.6
10 congenital contractures 10.6
11 arthrogryposis, distal, type 2b3 10.4
12 clubfoot 10.4
13 ptosis 10.3
14 clubfoot, congenital, with or without deficiency of long bones and/or mirror-image polydactyly 10.3
15 contractures, pterygia, and variable skeletal fusions syndrome 1a 10.3
16 arthrogryposis, distal, type 2b2 10.3
17 scoliosis 10.3
18 synostosis 10.3
19 oligohydramnios 10.3
20 myopathy 10.3
21 kearns-sayre syndrome 10.2
22 epicanthus 10.1
23 strabismus 10.1
24 astigmatism 10.1
25 keratoconus 10.1
26 mechanical strabismus 10.1
27 cleft palate, isolated 10.0
28 pectus excavatum 10.0
29 pulmonary hypertension 10.0
30 lung disease 10.0
31 multiple pterygium syndrome, escobar variant 9.4 TNNI2 PIEZO2

Graphical network of the top 20 diseases related to Arthrogryposis, Distal, Type 5:



Diseases related to Arthrogryposis, Distal, Type 5

Symptoms & Phenotypes for Arthrogryposis, Distal, Type 5

Human phenotypes related to Arthrogryposis, Distal, Type 5:

58 31 (show all 41)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 pectus excavatum 58 31 hallmark (90%) Very frequent (99-80%) HP:0000767
2 ptosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0000508
3 joint stiffness 58 31 hallmark (90%) Very frequent (99-80%) HP:0001387
4 ophthalmoplegia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000602
5 deeply set eye 58 31 hallmark (90%) Very frequent (99-80%) HP:0000490
6 dimple chin 31 hallmark (90%) HP:0010751
7 inguinal hernia 58 31 frequent (33%) Frequent (79-30%) HP:0000023
8 macrotia 58 31 frequent (33%) Frequent (79-30%) HP:0000400
9 abnormal electroretinogram 58 31 frequent (33%) Frequent (79-30%) HP:0000512
10 visual impairment 58 31 frequent (33%) Frequent (79-30%) HP:0000505
11 optic atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0000648
12 congenital finger flexion contractures 58 31 frequent (33%) Frequent (79-30%) HP:0005879
13 bilateral talipes equinovarus 58 31 frequent (33%) Frequent (79-30%) HP:0001776
14 arachnodactyly 58 31 frequent (33%) Frequent (79-30%) HP:0001166
15 triangular face 58 31 frequent (33%) Frequent (79-30%) HP:0000325
16 deviation of finger 58 31 frequent (33%) Frequent (79-30%) HP:0004097
17 absent palmar crease 58 31 frequent (33%) Frequent (79-30%) HP:0010489
18 scoliosis 31 occasional (7.5%) HP:0002650
19 hypermetropia 31 occasional (7.5%) HP:0000540
20 clinodactyly 31 HP:0030084
21 high palate 31 HP:0000218
22 short stature 31 HP:0004322
23 abnormality of retinal pigmentation 31 HP:0007703
24 arthrogryposis multiplex congenita 31 HP:0002804
25 decreased muscle mass 31 HP:0003199
26 protruding ear 31 HP:0000411
27 epicanthus 31 HP:0000286
28 restrictive ventilatory defect 31 HP:0002091
29 chin dimple 58 Very frequent (99-80%)
30 blepharophimosis 31 HP:0000581
31 keratoconus 31 HP:0000563
32 astigmatism 31 HP:0000483
33 keratoglobus 31 HP:0001119
34 decreased palmar creases 31 HP:0006184
35 distal arthrogryposis 31 HP:0005684
36 duane anomaly 31 HP:0009921
37 absent phalangeal crease 31 HP:0006109
38 decreased facial expression 31 HP:0004673
39 limited wrist extension 31 HP:0006251
40 abnormality of the rib cage 31 HP:0001547
41 firm muscles 31 HP:0003725

Symptoms via clinical synopsis from OMIM:

56
Chest Ribs Sternum Clavicles And Scapulae:
pectus excavatum

Head And Neck Eyes:
ptosis
abnormal electroretinogram
strabismus
ophthalmoplegia
blepharophimosis
more
Head And Neck Face:
triangular face
decreased facial expression

Head And Neck Mouth:
high-arched palate
reduced ability to open mouth (in some patients)

Head And Neck Ears:
prominent ears

Chest External Features:
hunched, anteverted shoulders

Skeletal Limbs:
limited forearm rotation
absent anterior cruciate ligament bilaterally (in some patients)

Skeletal Feet:
bilateral club feet

Skeletal Hands:
clinodactyly
long fingers
camptodactyly
limited wrist extension
congenital finger contractures
more
Growth Height:
short stature

Muscle Soft Tissue:
firm muscles
decreased muscle mass (especially in lower limbs)

Neurologic Central Nervous System:
normal intelligence
weak or absent tendon reflexes of knees and ankles (in some patients)

Respiratory Lung:
restrictive lung disease

Skeletal Spine:
spine stiffness
scoliosis (rare)

Skin Nails Hair Skin:
absent phalangeal creases
poorly formed palmar creases
dimples over large joints

Clinical features from OMIM:

108145

UMLS symptoms related to Arthrogryposis, Distal, Type 5:


ophthalmoplegia, ulnar deviation of the wrist

Drugs & Therapeutics for Arthrogryposis, Distal, Type 5

Drugs for Arthrogryposis, Distal, Type 5 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Adenosine Approved, Investigational 58-61-7 60961
2 Analgesics
3 Anti-Arrhythmia Agents
4 Neurotransmitter Agents
5 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 5

Cochrane evidence based reviews: oculomelic amyoplasia

Genetic Tests for Arthrogryposis, Distal, Type 5

Genetic tests related to Arthrogryposis, Distal, Type 5:

# Genetic test Affiliating Genes
1 Distal Arthrogryposis Type 2b 29 TNNI2
2 Oculomelic Amyoplasia 29 PIEZO2

Anatomical Context for Arthrogryposis, Distal, Type 5

MalaCards organs/tissues related to Arthrogryposis, Distal, Type 5:

40
Lung, Skeletal Muscle, Eye, Bone, Brain, Skin

Publications for Arthrogryposis, Distal, Type 5

Articles related to Arthrogryposis, Distal, Type 5:

(show all 19)
# Title Authors PMID Year
1
Distal arthrogryposis type IIB: unreported ophthalmic findings. 61 56 6
15103714 2004
2
Occurrence of Dandy-Walker anomaly in a familial case of distal arthogryposis type IIB. 61 56 6
11146470 2000
3
Distal arthrogryposis type IIB: further clinical delineation and 54-year follow-up of an index case. 61 56 6
8533802 1995
4
Mutations in PIEZO2 cause Gordon syndrome, Marden-Walker syndrome, and distal arthrogryposis type 5. 56 6
24726473 2014
5
Gain-of-function mutations in the mechanically activated ion channel PIEZO2 cause a subtype of Distal Arthrogryposis. 56 6
23487782 2013
6
Pulmonary disease is a component of distal arthrogryposis type 5. 56 6
17345626 2007
7
A new form of autosomal dominant arthrogryposis. 56 6
1941966 1991
8
Extending the spectrum of distal arthrogryposis. 61 56
8923937 1996
9
Arthrogryposis: a review and update. 56
19571066 2009
10
Juvenile macular dystrophy and forearm pronation-supination restriction presenting with features of distal arthrogryposis type 5. 56
19213027 2009
11
Arthrogryposis and congenital absence of the anterior cruciate ligament: a case report. 56
18819806 2009
12
Distal arthrogryposis 5: a dominant syndrome of peripheral contractures and ophthalmoplegia. 56
15389706 2004
13
A revised and extended classification of the distal arthrogryposes. 56
8923935 1996
14
Arthrogryposis, ophthalmoplegia, and retinopathy: confirmation of a new type of arthrogryposis. 56
8423615 1993
15
The distal arthrogryposes: delineation of new entities--review and nosologic discussion. 56
7039311 1982
16
Arthrogryposis multiplex congenita and the Turner phenotype. 56
5025860 1972
17
Dysmorphogenesis of joints, brain, and palate: a new dominantly inherited syndrome. 56
5678002 1968
18
Distal arthrogryposis type IIB: probable autosomal recessive inheritance. 61
10466425 1999
19
Distal arthrogryposis type IIB in a girl: autosomal recessive inheritance? 61
6535857 1984

Variations for Arthrogryposis, Distal, Type 5

ClinVar genetic disease variations for Arthrogryposis, Distal, Type 5:

6 (show all 25) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 TNNI2 NM_003282.4(TNNI2):c.521G>A (p.Arg174Gln)SNV Pathogenic 12435 rs104894311 11:1862753-1862753 11:1841523-1841523
2 TNNI2 NM_003282.4(TNNI2):c.466C>T (p.Arg156Ter)SNV Pathogenic 12436 rs104894312 11:1862698-1862698 11:1841468-1841468
3 TNNI2 NM_003282.4(TNNI2):c.496_498GAG[1] (p.Glu167del)short repeat Pathogenic 12439 rs199474800 11:1862728-1862730 11:1841498-1841500
4 PIEZO2 NM_022068.3(PIEZO2):c.8057G>A (p.Arg2686His)SNV Pathogenic 137629 rs587777450 18:10671726-10671726 18:10671729-10671729
5 PIEZO2 NM_022068.3(PIEZO2):c.8153G>T (p.Arg2718Leu)SNV Pathogenic 137631 rs587777452 18:10671630-10671630 18:10671633-10671633
6 PIEZO2 NM_022068.3(PIEZO2):c.8153G>C (p.Arg2718Pro)SNV Pathogenic 137632 rs587777452 18:10671630-10671630 18:10671633-10671633
7 PIEZO2 NM_022068.3(PIEZO2):c.2134A>G (p.Met712Val)SNV Pathogenic 137633 rs587777453 18:10789112-10789112 18:10789114-10789114
8 PIEZO2 NM_022068.3(PIEZO2):c.8215T>C (p.Ser2739Pro)SNV Pathogenic 137634 rs587777454 18:10671568-10671568 18:10671571-10671571
9 TNNI2 NM_003282.4(TNNI2):c.493A>T (p.Ile165Phe)SNV Pathogenic 694070 11:1862725-1862725 11:1841495-1841495
10 PIEZO2 NM_022068.3(PIEZO2):c.2993T>C (p.Met998Thr)SNV Pathogenic 235843 rs878853140 18:10762975-10762975 18:10762977-10762977
11 PIEZO2 NM_022068.3(PIEZO2):c.6662C>T (p.Thr2221Ile)SNV Pathogenic 235842 rs878853139 18:10696261-10696261 18:10696263-10696263
12 PIEZO2 NM_022068.3(PIEZO2):c.6668C>T (p.Ser2223Leu)SNV Pathogenic 235841 rs878853138 18:10696255-10696255 18:10696257-10696257
13 PIEZO2 NM_022068.3(PIEZO2):c.7067C>T (p.Thr2356Met)SNV Pathogenic 235840 rs878853137 18:10689744-10689744 18:10689746-10689746
14 PIEZO2 NM_022068.3(PIEZO2):c.8175_8177AGA[2] (p.Glu2727del)short repeat Pathogenic 235839 rs1555621138 18:10671600-10671602 18:10671603-10671605
15 PIEZO2 NM_022068.3(PIEZO2):c.8208del (p.Tyr2737fs)deletion Pathogenic 235838 rs878853135 18:10671575-10671575 18:10671578-10671578
16 PIEZO2 NM_022068.3(PIEZO2):c.2404A>T (p.Ile802Phe)SNV Pathogenic 96704 rs587777076 18:10784870-10784870 18:10784872-10784872
17 MYH3 NM_002470.4(MYH3):c.700G>A (p.Ala234Thr)SNV Likely pathogenic 14145 rs121913623 17:10551909-10551909 17:10648592-10648592
18 TNNI2 NM_003282.4(TNNI2):c.525G>T (p.Lys175Asn)SNV Likely pathogenic 212411 rs797046046 11:1862757-1862757 11:1841527-1841527
19 MYH3 NM_002470.4(MYH3):c.4826G>A (p.Arg1609Lys)SNV Likely pathogenic 522656 rs1555525264 17:10535923-10535923 17:10632606-10632606
20 TPM2 NM_213674.1(TPM2):c.307C>A (p.Gln103Lys)SNV Likely pathogenic 692080 9:35685711-35685711 9:35685714-35685714
21 TPM2 NM_213674.1(TPM2):c.826C>G (p.Gln276Glu)SNV Uncertain significance 548556 rs376668943 9:35682107-35682107 9:35682110-35682110
22 MYH3 NM_002470.4(MYH3):c.4129G>C (p.Glu1377Gln)SNV Uncertain significance 587607 rs1567553702 17:10538727-10538727 17:10635410-10635410
23 PIEZO2 NM_022068.3(PIEZO2):c.6136G>C (p.Glu2046Gln)SNV Uncertain significance 436313 rs200276831 18:10699142-10699142 18:10699144-10699144
24 TNNT3 NM_006757.4(TNNT3):c.762C>T (p.Gly254=)SNV Benign/Likely benign 31872 rs4727 11:1959707-1959707 11:1938477-1938477
25 TNNI2 NM_003282.4(TNNI2):c.60T>C (p.Ser20=)SNV Benign/Likely benign 94120 rs907610 11:1861760-1861760 11:1840530-1840530

UniProtKB/Swiss-Prot genetic disease variations for Arthrogryposis, Distal, Type 5:

73
# Symbol AA change Variation ID SNP ID
1 PIEZO2 p.Ile802Phe VAR_070938 rs587777076
2 PIEZO2 p.Arg2718Leu VAR_071304 rs587777452
3 PIEZO2 p.Arg2718Pro VAR_071305 rs587777452
4 PIEZO2 p.Ser2739Pro VAR_071306 rs587777454
5 PIEZO2 p.Met712Val VAR_071817 rs587777453

Expression for Arthrogryposis, Distal, Type 5

Search GEO for disease gene expression data for Arthrogryposis, Distal, Type 5.

Pathways for Arthrogryposis, Distal, Type 5

GO Terms for Arthrogryposis, Distal, Type 5

Sources for Arthrogryposis, Distal, Type 5

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