MCID: ART120
MIFTS: 41

Arthrogryposis, Distal, Type 3

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

Aliases & Classifications for Arthrogryposis, Distal, Type 3

MalaCards integrated aliases for Arthrogryposis, Distal, Type 3:

Name: Arthrogryposis, Distal, Type 3 54 24
Gordon Syndrome 24 56 71 52
Arthrogryposis Multiplex Congenita, Distal, Type Iia 24 71 69
Camptodactyly, Cleft Palate, and Clubfoot 24 71
Camptodactyly-Cleft Palate-Clubfoot Syndrome 56
Pseudohypoaldosteronism, Type Ii 69
Distal Arthrogryposis Type Iia 56
Distal Arthrogryposis Type 3 56
Arthrogryposis, Distal, 3 71
Da3 71

Characteristics:

Orphanet epidemiological data:

56
gordon syndrome
Inheritance: Autosomal dominant; Age of onset: Antenatal,Neonatal; Age of death: normal life expectancy;

OMIM:

54
Inheritance:
autosomal dominant


HPO:

32
arthrogryposis, distal, type 3:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Arthrogryposis, Distal, Type 3

OMIM : 54
DA3, or Gordon syndrome, is distinguished from other distal arthrogryposes by short stature and cleft palate (summary by Bamshad et al., 2009). There are 2 syndromes with features overlapping those of DA3 that are also caused by heterozygous mutation in PIEZO2: distal arthrogryposis type 5 (DA5; 108145) and Marden-Walker syndrome (MWKS; 248700), which are distinguished by the presence of ocular abnormalities and mental retardation, respectively. McMillin et al. (2014) suggested that the 3 disorders may represent variable expressivity of the same condition. For a phenotypic description and a discussion of genetic heterogeneity of distal arthrogryposis, see DA1 (108120). (114300)

MalaCards based summary : Arthrogryposis, Distal, Type 3, also known as gordon syndrome, is related to pseudohypoaldosteronism, type iie and arthrogryposis, distal, type 5, and has symptoms including short stature, scoliosis and cleft palate. An important gene associated with Arthrogryposis, Distal, Type 3 is PIEZO2 (Piezo Type Mechanosensitive Ion Channel Component 2), and among its related pathways/superpathways are PI3K / Akt Signaling and Diuretics Pathway, Pharmacodynamics. The drugs Buspirone and Cocaine have been mentioned in the context of this disorder. Affiliated tissues include cerebellum, and related phenotypes are Increased cell death HMECs cells and Transferrin accumulation in the perinuclear area

UniProtKB/Swiss-Prot : 71 Arthrogryposis, distal, 3: 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. DA3 features include short stature and cleft palate.

Related Diseases for Arthrogryposis, Distal, Type 3

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

(show all 31)
id Related Disease Score Top Affiliating Genes
1 pseudohypoaldosteronism, type iie 11.0
2 arthrogryposis, distal, type 5 10.8
3 encephalopathy due to defective mitochondrial and peroxisomal fission 2 10.4 PIEZO2 WNK4
4 familial isolated pituitary adenoma 10.2 WNK1 WNK4
5 bestrophinopathy 10.0 REN SLC12A3
6 broad ligament malignant neoplasm 10.0 REN SLC12A3
7 listeria meningitis 10.0 REN SLC12A3
8 bartter syndrome, type 3 10.0 REN SLC12A3
9 astrakhan spotted fever 9.9 REN SLC12A3
10 hypertension, early-onset, autosomal dominant, with exacerbation in pregnancy 9.9 NR3C2 REN
11 spondyloepimetaphyseal dysplasia, faden-alkuraya type 9.9 REN SLC12A3
12 long qt syndrome 13 9.9 NR3C2 REN
13 adenocarcinoma 9.8 NR3C2 REN
14 hypoaldosteronism, congenital, due to cmo ii deficiency 9.8 NR3C2 REN
15 trabecular follicular adenocarcinoma 9.8 NR3C2 REN
16 pediatric angiosarcoma 9.8 REN SLC12A3
17 bronchiectasis 9.8 NR3C2 REN
18 north american indian childhood cirrhosis 9.8 NR3C2 REN
19 cardiovascular organ benign neoplasm 9.8 NR3C2 REN
20 panuveitis 9.7 NR3C2 REN
21 bronchiectasis with or without elevated sweat chloride 2 9.7 NR3C2 REN
22 renal clear cell carcinoma 9.6 NR3C2 REN
23 retinal vein occlusion 9.5 NR3C2 REN
24 craniosynostosis 9.5 NR3C2 REN
25 bronchiectasis with or without elevated sweat chloride 1 9.4 NR3C2 REN
26 perrault syndrome 9.2 NR3C2 REN
27 rhinitis 9.1 REN SLC12A3 WNK1 WNK4
28 microphthalmia, isolated, with coloboma 7 8.9 NR3C2 REN WNK1 WNK4
29 pulmonary fibrosis 8.8 NR3C2 SLC12A3 WNK1 WNK4
30 hypertension, essential 8.3 NR3C2 REN SLC12A3 WNK1 WNK4
31 marden-walker syndrome 7.9 NR3C2 PIEZO2 REN SLC12A3 WNK1 WNK4

Graphical network of the top 20 diseases related to Arthrogryposis, Distal, Type 3:



Diseases related to Arthrogryposis, Distal, Type 3

Symptoms & Phenotypes for Arthrogryposis, Distal, Type 3

Symptoms via clinical synopsis from OMIM:

54

Growth- Height:
short stature

Head And Neck- Eyes:
ptosis
epicanthal folds
ophthalmoplegia (in some patients)

Skeletal- Spine:
kyphoscoliosis
lumbar lordosis
thoracolumbar scoliosis

Skeletal- Feet:
camptodactyly
talipes equinovarus
overlapping toes

Chest- External Features:
pectus excavatum
sloping shoulders

Skeletal- Pelvis:
congenital hip dislocation
limited hip abduction

Skeletal- Limbs:
knee flexion contractures

Neurologic- Central Nervous System:
chiari i malformation of the cerebellum (in some patients)

Head And Neck- Mouth:
high-arched palate
cleft palate
bifid uvula
submucous cleft

Head And Neck- Face:
micrognathia
facial asymmetry (mild)

Genitourinary- Internal Genitalia Male:
cryptorchidism

Head And Neck- Neck:
short neck
mild neck webbing

Skeletal- Hands:
short fingers
single transverse palmar creases
ulnar deviation
cutaneous syndactyly
camptodactyly of proximal interphalangeal joint
more
Skin Nails & Hair- Skin:
single transverse palmar creases
absence of interphalangeal creases

Muscle Soft Tissue:
decreased muscle mass (especially of limbs)


Clinical features from OMIM:

114300

Human phenotypes related to Arthrogryposis, Distal, Type 3:

56 32 (show all 38)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 short stature 56 32 occasional (7.5%) Occasional (29-5%) HP:0004322
2 scoliosis 56 32 occasional (7.5%) Occasional (29-5%) HP:0002650
3 cleft palate 56 32 occasional (7.5%) Occasional (29-5%) HP:0000175
4 cryptorchidism 56 32 occasional (7.5%) Occasional (29-5%) HP:0000028
5 pectus excavatum 56 32 occasional (7.5%) Occasional (29-5%) HP:0000767
6 finger syndactyly 56 32 occasional (7.5%) Occasional (29-5%) HP:0006101
7 high palate 56 32 frequent (33%) Frequent (79-30%) HP:0000218
8 facial asymmetry 56 32 occasional (7.5%) Occasional (29-5%) HP:0000324
9 talipes 56 32 hallmark (90%) Very frequent (99-80%) HP:0001883
10 decreased muscle mass 56 32 frequent (33%) Frequent (79-30%) HP:0003199
11 hearing impairment 56 32 occasional (7.5%) Occasional (29-5%) HP:0000365
12 limitation of joint mobility 56 32 occasional (7.5%) Occasional (29-5%) HP:0001376
13 clinodactyly of the 5th finger 56 32 occasional (7.5%) Occasional (29-5%) HP:0004209
14 camptodactyly of finger 56 32 hallmark (90%) Very frequent (99-80%) HP:0100490
15 ptosis 32 HP:0000508
16 micrognathia 32 HP:0000347
17 lumbar hyperlordosis 32 HP:0002938
18 kyphoscoliosis 32 HP:0002751
19 arthrogryposis multiplex congenita 32 HP:0002804
20 talipes equinovarus 32 HP:0001762
21 short neck 32 HP:0000470
22 bifid uvula 32 HP:0000193
23 knee flexion contracture 32 HP:0006380
24 congenital hip dislocation 32 HP:0001374
25 epicanthus 32 HP:0000286
26 ophthalmoplegia 32 occasional (7.5%) HP:0000602
27 single transverse palmar crease 32 HP:0000954
28 thoracolumbar scoliosis 32 HP:0002944
29 decreased hip abduction 32 HP:0003184
30 distal arthrogryposis 32 HP:0005684
31 down-sloping shoulders 32 HP:0200021
32 submucous cleft hard palate 32 HP:0000176
33 cutaneous finger syndactyly 32 HP:0010554
34 short phalanx of finger 32 HP:0009803
35 camptodactyly of toe 32 HP:0001836
36 overlapping toe 32 HP:0001845
37 ulnar deviation of the hand or of fingers of the hand 32 HP:0001193
38 abnormality of the rib cage 32 HP:0001547

GenomeRNAi Phenotypes related to Arthrogryposis, Distal, Type 3 according to GeneCards Suite gene sharing:

26
id Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased cell death HMECs cells GR00103-A-0 9.13 NR3C2 WNK1 WNK4
2 Transferrin accumulation in the perinuclear area GR00356-A-3 8.62 WNK1 WNK4

MGI Mouse Phenotypes related to Arthrogryposis, Distal, Type 3:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.35 NR3C2 REN SLC12A3 WNK1 WNK4
2 renal/urinary system MP:0005367 9.02 NR3C2 REN SLC12A3 WNK1 WNK4

Drugs & Therapeutics for Arthrogryposis, Distal, Type 3

Drugs for Arthrogryposis, Distal, Type 3 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 24)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Buspirone Approved, Investigational Phase 2 36505-84-7 2477
2
Cocaine Approved, Illicit Phase 2 50-36-2 5760 446220
3
Dopamine Approved Phase 2 51-61-6, 62-31-7 681
4
Methylphenidate Approved, Investigational Phase 2 113-45-1 4158
5 Neurotransmitter Agents Phase 2
6 Peripheral Nervous System Agents Phase 2
7 Anesthetics Phase 2
8 Anesthetics, Local Phase 2
9 Anti-Anxiety Agents Phase 2
10 Central Nervous System Depressants Phase 2
11 Central Nervous System Stimulants Phase 2
12 Dopamine Agents Phase 2
13 Dopamine Uptake Inhibitors Phase 2
14 Neurotransmitter Uptake Inhibitors Phase 2
15 Psychotropic Drugs Phase 2
16
Serotonin Phase 2 50-67-9 5202
17 Serotonin Agents Phase 2
18 Tranquilizing Agents Phase 2
19 Vasoconstrictor Agents Phase 2
20
Adenosine Approved, Investigational 58-61-7 60961
21
Menthol Approved 2216-51-5 16666
22 Analgesics
23 Anti-Arrhythmia Agents
24 Vasodilator Agents

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Psychopharmacology for Cocaine Dependence - Buspirone Completed NCT01267292 Phase 2 Buspirone;Placebo for Buspirone;Methylphenidate;Placebo for Methylphenidate
2 Study of Resting and Exercising Body Functioning in Freeman-Sheldon Syndrome and Related Conditions Unknown status NCT01306994
3 Survey Study and Records Review of Treatment Outcomes in Freeman-Sheldon Syndrome Recruiting NCT01144741

Search NIH Clinical Center for Arthrogryposis, Distal, Type 3

Genetic Tests for Arthrogryposis, Distal, Type 3

Genetic tests related to Arthrogryposis, Distal, Type 3:

id Genetic test Affiliating Genes
1 Arthrogryposis, Distal, Type 3 24 PIEZO2

Anatomical Context for Arthrogryposis, Distal, Type 3

MalaCards organs/tissues related to Arthrogryposis, Distal, Type 3:

39
Cerebellum

Publications for Arthrogryposis, Distal, Type 3

Variations for Arthrogryposis, Distal, Type 3

UniProtKB/Swiss-Prot genetic disease variations for Arthrogryposis, Distal, Type 3:

71
id Symbol AA change Variation ID SNP ID
1 PIEZO2 p.Arg2686His VAR_071303 rs587777450

ClinVar genetic disease variations for Arthrogryposis, Distal, Type 3:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 PIEZO2 NM_022068.3(PIEZO2): c.8238_8245delGACTAGAG (p.Trp2746Terfs) deletion Pathogenic rs724159993 GRCh37 Chromosome 18, 10671538: 10671545
2 PIEZO2 NM_022068.3(PIEZO2): c.8057G> A (p.Arg2686His) single nucleotide variant Pathogenic rs587777450 GRCh38 Chromosome 18, 10671729: 10671729

Expression for Arthrogryposis, Distal, Type 3

Search GEO for disease gene expression data for Arthrogryposis, Distal, Type 3.

Pathways for Arthrogryposis, Distal, Type 3

Pathways related to Arthrogryposis, Distal, Type 3 according to GeneCards Suite gene sharing:

id Super pathways Score Top Affiliating Genes
1 10.9 WNK1 WNK4
2 10.26 SLC12A3 WNK1 WNK4

GO Terms for Arthrogryposis, Distal, Type 3

Biological processes related to Arthrogryposis, Distal, Type 3 according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 ion transport GO:0006811 9.46 PIEZO2 SLC12A3 WNK1 WNK4
2 chloride transport GO:0006821 9.26 SLC12A3 WNK4
3 negative regulation of pancreatic juice secretion GO:0090188 8.96 WNK1 WNK4
4 regulation of cellular process GO:0050794 8.62 WNK1 WNK4

Molecular functions related to Arthrogryposis, Distal, Type 3 according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 chloride channel inhibitor activity GO:0019869 8.62 WNK1 WNK4

Sources for Arthrogryposis, Distal, Type 3

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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