DA3
MCID: ART120
MIFTS: 52

Arthrogryposis, Distal, Type 3 (DA3)

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 3

MalaCards integrated aliases for Arthrogryposis, Distal, Type 3:

Name: Arthrogryposis, Distal, Type 3 58 41
Gordon Syndrome 58 77 54 60 76 56
Arthrogryposis Multiplex Congenita, Distal, Type Iia 58 76 74
Camptodactyly, Cleft Palate, and Clubfoot 58 54 76
Da3 58 54 76
Distal Arthrogryposis Type 3 54 60
Camptodactyly-Cleft Palate-Clubfoot Syndrome 60
Pseudohypoaldosteronism, Type Ii 74
Distal Arthrogryposis Type Iia 60
Arthrogryposis Distal Type 3 54
Arthrogryposis, Distal, 3 76

Characteristics:

Orphanet epidemiological data:

60
gordon syndrome
Inheritance: Autosomal dominant; Age of onset: Antenatal,Neonatal; Age of death: normal life expectancy;

OMIM:

58
Inheritance:
autosomal dominant


HPO:

33
arthrogryposis, distal, type 3:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Arthrogryposis, Distal, Type 3

NIH Rare Diseases : 54 Gordon Syndrome is a rare, inherited disorder that affects movement in the joints of the upper and lower limbs, also known as distal arthrogryposis. People with this disorder can be born with several fingers fixed in a flexed position (camptodactyly), clubfoot, and an opening in the roof of the mouth (cleft palate). Their joints are often very stiff or unable to move. Intelligence is usually normal. The range and severity of symptoms may vary from person to person. Gordon syndrome is caused by genetic changes (mutations) in the PIEZO2 gene and can be inherited in an autosomal dominant pattern. Gordon syndrome is diagnosed by clinical examination and genetic testing. Treatment is directed at the symptoms and includes surgery and physical therapy to loosen the joints. People with Gordon syndrome often have reduced mobility, but Gordon syndrome doesn't usually result in other health problems.

MalaCards based summary : Arthrogryposis, Distal, Type 3, also known as gordon syndrome, is related to baker-gordon syndrome and pseudohypoaldosteronism, type iid. 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 Agents Acting on the Renin-Angiotensin System Pathway, Pharmacodynamics. The drugs Methylphenidate and Cocaine have been mentioned in the context of this disorder. Affiliated tissues include testes, myeloid and cerebellum, and related phenotypes are camptodactyly of finger and talipes

OMIM : 58 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)

UniProtKB/Swiss-Prot : 76 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.

Wikipedia : 77 Arthrogryposis multiplex congenita (AMC), or simply arthrogryposis, describes congenital joint... more...

Related Diseases for Arthrogryposis, Distal, Type 3

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 4 Arthrogryposis, Distal, Type 1b
Arthrogryposis, Distal, Type 5d

Diseases related to Arthrogryposis, Distal, Type 3 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 37)
# Related Disease Score Top Affiliating Genes
1 baker-gordon syndrome 12.4
2 pseudohypoaldosteronism, type iid 11.4
3 keratoderma, palmoplantar, with nail dystrophy and hereditary motor-sensory neuropathy 11.2
4 keratoderma palmoplantar spastic paralysis 11.2
5 arthrogryposis, distal, type 5 11.1
6 cleft palate, isolated 10.1
7 distal arthrogryposis 10.1
8 bartter disease 10.0 REN SLC12A3
9 renal hypertension 9.9 REN SLC12A3
10 bartter syndrome, type 3 9.9 REN SLC12A3
11 mineral metabolism disease 9.9 REN SLC12A3
12 gitelman syndrome 9.9 REN SLC12A3
13 metabolic acidosis 9.9 WNK1 WNK4
14 aase-smith syndrome i 9.9
15 marden-walker syndrome 9.9
16 dominant cleft palate 9.9
17 hydrocephalus-cleft palate-joint contractures syndrome 9.9
18 pseudohypoaldosteronism, type i, autosomal dominant 9.9 NR3C2 REN
19 apparent mineralocorticoid excess 9.9 NR3C2 REN
20 anuria 9.9 NR3C2 REN
21 hyperaldosteronism, familial, type i 9.9 NR3C2 REN
22 pseudohypoaldosteronism, type i, autosomal recessive 9.8 NR3C2 REN
23 adrenal cortex disease 9.8 NR3C2 REN
24 adrenal gland disease 9.8 NR3C2 REN
25 cortisone reductase deficiency 9.8 NR3C2 REN
26 heart valve disease 9.8 NR3C2 REN
27 renal tubular acidosis 9.7 NR3C2 REN
28 renal fibrosis 9.7 NR3C2 REN
29 congestive heart failure 9.6 NR3C2 REN
30 liddle syndrome 1 9.6 NR3C2 REN WNK4
31 hypokalemia 9.5 NR3C2 REN SLC12A3
32 conn's syndrome 9.5 NR3C2 REN
33 renal tubular transport disease 9.4 REN SLC12A3 WNK1 WNK4
34 familial hypertension 9.3 NR3C2 REN WNK1 WNK4
35 pseudohyperkalemia, familial, 2, due to red cell leak 9.3 NR3C2 REN WNK1 WNK4
36 pseudohypoaldosteronism 9.0 NR3C2 REN SLC12A3 WNK1 WNK4
37 hypertension, essential 8.9 NR3C2 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

Human phenotypes related to Arthrogryposis, Distal, Type 3:

60 33 (show all 40)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 camptodactyly of finger 60 33 hallmark (90%) Very frequent (99-80%) HP:0100490
2 talipes 60 33 hallmark (90%) Very frequent (99-80%) HP:0001883
3 high palate 60 33 frequent (33%) Frequent (79-30%) HP:0000218
4 decreased muscle mass 60 33 frequent (33%) Frequent (79-30%) HP:0003199
5 pectus excavatum 60 33 occasional (7.5%) Occasional (29-5%) HP:0000767
6 finger syndactyly 60 33 occasional (7.5%) Occasional (29-5%) HP:0006101
7 scoliosis 60 33 occasional (7.5%) Occasional (29-5%) HP:0002650
8 hearing impairment 60 33 occasional (7.5%) Occasional (29-5%) HP:0000365
9 short stature 60 33 occasional (7.5%) Occasional (29-5%) HP:0004322
10 cleft palate 60 33 occasional (7.5%) Occasional (29-5%) HP:0000175
11 limitation of joint mobility 60 33 occasional (7.5%) Occasional (29-5%) HP:0001376
12 cryptorchidism 60 33 occasional (7.5%) Occasional (29-5%) HP:0000028
13 clinodactyly of the 5th finger 60 33 occasional (7.5%) Occasional (29-5%) HP:0004209
14 facial asymmetry 60 33 occasional (7.5%) Occasional (29-5%) HP:0000324
15 ophthalmoplegia 33 occasional (7.5%) HP:0000602
16 global developmental delay 33 very rare (1%) HP:0001263
17 intellectual disability, mild 33 very rare (1%) HP:0001256
18 short neck 33 HP:0000470
19 ptosis 33 HP:0000508
20 micrognathia 33 HP:0000347
21 epicanthus 33 HP:0000286
22 arthrogryposis multiplex congenita 33 HP:0002804
23 congenital hip dislocation 33 HP:0001374
24 talipes equinovarus 33 HP:0001762
25 kyphoscoliosis 33 HP:0002751
26 down-sloping shoulders 33 HP:0200021
27 cutaneous finger syndactyly 33 HP:0010554
28 bifid uvula 33 HP:0000193
29 single transverse palmar crease 33 HP:0000954
30 submucous cleft hard palate 33 HP:0000176
31 knee flexion contracture 33 HP:0006380
32 short phalanx of finger 33 HP:0009803
33 lumbar hyperlordosis 33 HP:0002938
34 decreased hip abduction 33 HP:0003184
35 camptodactyly of toe 33 HP:0001836
36 overlapping toe 33 HP:0001845
37 thoracolumbar scoliosis 33 HP:0002944
38 distal arthrogryposis 33 HP:0005684
39 ulnar deviation of the hand or of fingers of the hand 33 HP:0001193
40 abnormality of the rib cage 33 HP:0001547

Symptoms via clinical synopsis from OMIM:

58
Head And Neck Neck:
short neck
mild neck webbing

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

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

Genitourinary Internal Genitalia Male:
cryptorchidism

Skeletal Feet:
talipes equinovarus
camptodactyly
overlapping toes

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

Neurologic Central Nervous System:
chiari i malformation of the cerebellum (in some patients)
intellectual disability, mild (in some patients)
psychomotor delay, mild (in some patients)

Chest External Features:
pectus excavatum
sloping shoulders

Growth Height:
short stature

Head And Neck Face:
micrognathia
facial asymmetry (mild)

Skeletal Pelvis:
congenital hip dislocation
limited hip abduction

Skeletal Spine:
kyphoscoliosis
thoracolumbar scoliosis
lumbar lordosis

Skeletal Limbs:
knee flexion contractures

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

Clinical features from OMIM:

114300

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

27
# 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:

47
# 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 45)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Methylphenidate Approved, Investigational Phase 2 113-45-1 4158
2
Cocaine Approved, Illicit Phase 2 50-36-2 446220 5760
3
Buspirone Approved, Investigational Phase 2 36505-84-7 2477
4
Dopamine Approved Phase 2 62-31-7, 51-61-6 681
5 Anesthetics, Local Phase 2
6 Neurotransmitter Agents Phase 2
7 Dopamine Agents Phase 2
8 Neurotransmitter Uptake Inhibitors Phase 2
9 Anesthetics Phase 2
10 Psychotropic Drugs Phase 2
11 Anti-Anxiety Agents Phase 2
12 Central Nervous System Depressants Phase 2
13 Dopamine Uptake Inhibitors Phase 2
14 Vasoconstrictor Agents Phase 2
15 Tranquilizing Agents Phase 2
16 Central Nervous System Stimulants Phase 2
17 Serotonin Receptor Agonists Phase 2
18 Serotonin Agents Phase 2
19 Peripheral Nervous System Agents Phase 2
20
Serotonin Investigational, Nutraceutical Phase 2 50-67-9 5202
21
Cytarabine Approved, Experimental, Investigational Early Phase 1 147-94-4, 65-46-3 6253
22
Daunorubicin Approved Early Phase 1 20830-81-3 30323
23
Atovaquone Approved Early Phase 1 95233-18-4 74989
24
Etoposide Approved Early Phase 1 33419-42-0 36462
25
Adenosine Approved, Investigational 58-61-7 60961
26 Etoposide phosphate Early Phase 1
27 Antimetabolites Early Phase 1
28 Anti-Bacterial Agents Early Phase 1
29 Immunologic Factors Early Phase 1
30 Antiprotozoal Agents Early Phase 1
31 Topoisomerase Inhibitors Early Phase 1
32 Gemtuzumab Early Phase 1
33 Antineoplastic Agents, Phytogenic Early Phase 1
34 Antimalarials Early Phase 1
35 Anti-Infective Agents Early Phase 1
36 Antiviral Agents Early Phase 1
37 Antimetabolites, Antineoplastic Early Phase 1
38 Antiparasitic Agents Early Phase 1
39 Immunosuppressive Agents Early Phase 1
40 Antibiotics, Antitubercular Early Phase 1
41 Antineoplastic Agents, Immunological Early Phase 1
42 Calcineurin Inhibitors
43 Vasodilator Agents
44 Anti-Arrhythmia Agents
45 Analgesics

Interventional clinical trials:


# 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 Survey Study and Records Review of Treatment Outcomes in Freeman-Sheldon Syndrome Recruiting NCT01144741
3 Atovaquone (Mepron®) Combined With Conventional Chemotherapy for de Novo Acute Myeloid Leukemia (AML) Recruiting NCT03568994 Early Phase 1 Atovaquone;Cytarabine;Daunorubicin;Etoposide;Gemtuzumab Ozogamicin
4 Major Activation Of NCC in Graft Urinary Exosomes Completed NCT03503461
5 Study of Resting and Exercising Body Functioning in Freeman-Sheldon Syndrome and Related Conditions Not yet recruiting NCT01306994

Search NIH Clinical Center for Arthrogryposis, Distal, Type 3

Genetic Tests for Arthrogryposis, Distal, Type 3

Anatomical Context for Arthrogryposis, Distal, Type 3

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

42
Testes, Myeloid, Cerebellum, Kidney

Publications for Arthrogryposis, Distal, Type 3

Articles related to Arthrogryposis, Distal, Type 3:

(show all 21)
# Title Authors Year
1
Renal sodium and magnesium reabsorption are not coupled in a mouse model of Gordon syndrome. ( 30030908 )
2018
2
Three cases of Gordon syndrome with dominant KLHL3 mutations. ( 28222034 )
2017
3
Familial Gordon syndrome associated with a PIEZO2 mutation. ( 27714920 )
2017
4
Gordon syndrome: literature review and a report of two cases. ( 24878349 )
2015
5
Gordon Syndrome: a continuing story. ( 25503323 )
2015
6
Mutations in PIEZO2 cause Gordon syndrome, Marden-Walker syndrome, and distal arthrogryposis type 5. ( 24726473 )
2014
7
Molecular insights from dysregulation of the thiazide-sensitive WNK/SPAK/NCC pathway in the kidney: Gordon syndrome and thiazide-induced hyponatraemia. ( 23683032 )
2013
8
Familial or genetic primary aldosteronism and Gordon syndrome. ( 21565671 )
2011
9
Elevated plasma asymmetric dimethyl-L-arginine in a patient with Gordon syndrome. ( 16998213 )
2007
10
Gordon syndrome and succinylcholine. ( 16435216 )
2005
11
A family with distal arthrogryposis and cleft palate: possible overlap between Gordon syndrome and Aase-Smith syndrome. ( 11152147 )
2001
12
Phenotypic and genetic heterogeneity of familial hyperkalaemic hypertension (Gordon syndrome). ( 11903313 )
2001
13
Familial hyperkalemic hypertension (Gordon syndrome): evidence for phenotypic variability in a study of 7 families. ( 11692471 )
2001
14
The Gordon syndrome revisited. ( 11081133 )
2000
15
New syndrome or severe expression of Gordon syndrome? A case report. ( 9018417 )
1997
16
Furosemide versus thiazide in Gordon syndrome. ( 8831092 )
1996
17
Neonatal presentation of Gordon syndrome. ( 8859273 )
1996
18
Distal arthrogryposis with autosomal dominant inheritance and reduced penetrance in females: the Gordon syndrome. ( 8370149 )
1993
19
The Gordon syndrome: autosomal dominant cleft palate, camptodactyly, and club feet. ( 7258227 )
1981
20
The Gordon syndrome. ( 7218283 )
1980
21
Camptodactyly, cleft palate, and club foot (the Gordon syndrome). A report of a large pedigree. ( 458832 )
1979

Variations for Arthrogryposis, Distal, Type 3

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

76
# Symbol AA change Variation ID SNP ID
1 PIEZO2 p.Arg2686His VAR_071303 rs587777450

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

6
# 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.8238_8245delGACTAGAG (p.Trp2746Terfs) deletion Pathogenic rs724159993 GRCh38 Chromosome 18, 10671541: 10671548
3 PIEZO2 NM_022068.3(PIEZO2): c.8057G> A (p.Arg2686His) single nucleotide variant Pathogenic rs587777450 GRCh38 Chromosome 18, 10671729: 10671729
4 PIEZO2 NM_022068.3(PIEZO2): c.8057G> A (p.Arg2686His) single nucleotide variant Pathogenic rs587777450 GRCh37 Chromosome 18, 10671726: 10671726
5 PIEZO2 NM_022068.3(PIEZO2): c.4073C> T (p.Thr1358Met) single nucleotide variant Uncertain significance rs777349822 GRCh37 Chromosome 18, 10752653: 10752653
6 PIEZO2 NM_022068.3(PIEZO2): c.4073C> T (p.Thr1358Met) single nucleotide variant Uncertain significance rs777349822 GRCh38 Chromosome 18, 10752655: 10752655

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:

# Super pathways Score Top Affiliating Genes
1 11.12 WNK1 WNK4
2
Show member pathways
10.86 NR3C2 REN
3 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:

# Name GO ID Score Top Affiliating Genes
1 ion transport GO:0006811 9.73 PIEZO2 SLC12A3 WNK1 WNK4
2 ion homeostasis GO:0050801 9.4 WNK1 WNK4
3 positive regulation of ion transmembrane transporter activity GO:0032414 9.37 WNK1 WNK4
4 positive regulation of sodium ion transmembrane transporter activity GO:2000651 9.32 WNK1 WNK4
5 negative regulation of sodium ion transport GO:0010766 9.26 WNK1 WNK4
6 positive regulation of potassium ion import GO:1903288 9.16 WNK1 WNK4
7 negative regulation of pancreatic juice secretion GO:0090188 8.96 WNK1 WNK4
8 regulation of cellular process GO:0050794 8.62 WNK1 WNK4

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

# Name GO ID Score Top Affiliating Genes
1 chloride channel inhibitor activity GO:0019869 8.96 WNK1 WNK4
2 potassium channel inhibitor activity GO:0019870 8.62 WNK1 WNK4

Sources for Arthrogryposis, Distal, Type 3

3 CDC
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
41 LOVD
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45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
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52 NDF-RT
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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