DA3
MCID: ART120
MIFTS: 49

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, Skin diseases, Smell/Taste diseases

Aliases & Classifications for Arthrogryposis, Distal, Type 3

MalaCards integrated aliases for Arthrogryposis, Distal, Type 3:

Name: Arthrogryposis, Distal, Type 3 56 39
Gordon Syndrome 56 12 74 52 58 73 54 43
Da3 56 12 52 73
Arthrogryposis Multiplex Congenita, Distal, Type Iia 56 73 71
Camptodactyly, Cleft Palate, and Clubfoot 56 52 73
Distal Arthrogryposis Type 3 12 52 58
Camptodactyly-Cleft Palate-Clubfoot Syndrome 12 58
Distal Arthrogryposis Multiplex Congenita Type Iia 12
Pseudohypoaldosteronism, Type Ii 71
Distal Arthrogryposis Type Iia 58
Arthrogryposis Distal Type 3 52
Arthrogryposis, Distal, 3 73

Characteristics:

Orphanet epidemiological data:

58
gordon syndrome
Inheritance: Autosomal dominant; Age of onset: Antenatal,Neonatal; Age of death: normal life expectancy;

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
variable features may be present
mild form may be comprised of short stature, clubfeet, and distal contractures


HPO:

31
arthrogryposis, distal, type 3:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Developmental anomalies during embryogenesis


Summaries for Arthrogryposis, Distal, Type 3

NIH Rare Diseases : 52 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 metabolic acidosis and gitelman syndrome. 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 drug Calcineurin Inhibitors has been mentioned in the context of this disorder. Affiliated tissues include testes, kidney and bone, and related phenotypes are talipes and camptodactyly of finger

Disease Ontology : 12 A distal arthrogryposis characterized by distal arthrogryposis with short stature and cleft palate that has material basis in heterozygous mutation in PIEZO2 on chromosome 18p11.22-p11.21.

OMIM : 56 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 : 73 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 : 74 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 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 3 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 63)
# Related Disease Score Top Affiliating Genes
1 metabolic acidosis 29.6 WNK4 WNK1
2 gitelman syndrome 28.5 WNK4 WNK1 SLC12A3 REN
3 familial hypertension 28.3 WNK4 WNK1 REN NR3C2
4 pseudohypoaldosteronism 27.8 WNK4 WNK1 SLC12A3 REN NR3C2
5 baker-gordon syndrome 12.5
6 keratoderma, palmoplantar, with nail dystrophy and hereditary motor-sensory neuropathy 11.4
7 arthrogryposis, distal, type 5 11.2
8 marden-walker syndrome 11.2
9 pseudohypoaldosteronism, type iid 11.2
10 cleft palate, isolated 10.3
11 alkuraya-kucinskas syndrome 10.2
12 distal arthrogryposis 10.2
13 congenital amyoplasia 10.2
14 pseudohypoaldosteronism, type iia 10.0
15 bartter syndrome, type 3 9.9 SLC12A3 REN
16 neuropathy, hereditary sensory and autonomic, type iia 9.9 WNK4 WNK1
17 clubfoot, congenital, with or without deficiency of long bones and/or mirror-image polydactyly 9.9
18 epicanthus 9.9
19 aase-smith syndrome i 9.9
20 pectus excavatum 9.9
21 cryptorchidism, unilateral or bilateral 9.9
22 myopathy, congenital 9.9
23 facial dysmorphism, cleft palate, hearing loss, and camptodactyly 9.9
24 pseudohypoaldosteronism, type iib 9.9
25 pseudohypoaldosteronism, type iic 9.9
26 alacrima, achalasia, and mental retardation syndrome 9.9
27 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 9.9
28 ptosis 9.9
29 clubfoot 9.9
30 myopathy 9.9
31 malignant hyperthermia 9.9
32 congenital contractures 9.9
33 dominant cleft palate 9.9
34 hypoadrenalism 9.9
35 hypoaldosteronism 9.9
36 familial hyperaldosteronism 9.9
37 hypotonia 9.9
38 chondrocalcinosis 9.8 SLC12A3 REN
39 renal hypertension 9.8 SLC12A3 REN
40 diabetes insipidus, nephrogenic, autosomal 9.8 SLC12A3 REN
41 autonomic neuropathy 9.8 WNK1 REN
42 pseudohypoaldosteronism, type i, autosomal dominant 9.7 REN NR3C2
43 anuria 9.7 REN NR3C2
44 steroid inherited metabolic disorder 9.7 REN NR3C2
45 pseudohypoaldosteronism, type i, autosomal recessive 9.7 REN NR3C2
46 adrenal cortex disease 9.7 REN NR3C2
47 hypertensive heart disease 9.7 REN NR3C2
48 adrenal gland disease 9.7 REN NR3C2
49 heart valve disease 9.6 REN NR3C2
50 pulmonary edema 9.6 REN NR3C2

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:

58 31 (show all 40)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 talipes 58 31 hallmark (90%) Very frequent (99-80%) HP:0001883
2 camptodactyly of finger 58 31 hallmark (90%) Very frequent (99-80%) HP:0100490
3 high palate 58 31 frequent (33%) Frequent (79-30%) HP:0000218
4 decreased muscle mass 58 31 frequent (33%) Frequent (79-30%) HP:0003199
5 pectus excavatum 58 31 occasional (7.5%) Occasional (29-5%) HP:0000767
6 finger syndactyly 58 31 occasional (7.5%) Occasional (29-5%) HP:0006101
7 scoliosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002650
8 hearing impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0000365
9 short stature 58 31 occasional (7.5%) Occasional (29-5%) HP:0004322
10 cryptorchidism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000028
11 cleft palate 58 31 occasional (7.5%) Occasional (29-5%) HP:0000175
12 limitation of joint mobility 58 31 occasional (7.5%) Occasional (29-5%) HP:0001376
13 clinodactyly of the 5th finger 58 31 occasional (7.5%) Occasional (29-5%) HP:0004209
14 facial asymmetry 58 31 occasional (7.5%) Occasional (29-5%) HP:0000324
15 ophthalmoplegia 31 occasional (7.5%) HP:0000602
16 global developmental delay 31 very rare (1%) HP:0001263
17 intellectual disability, mild 31 very rare (1%) HP:0001256
18 short neck 31 HP:0000470
19 ptosis 31 HP:0000508
20 micrognathia 31 HP:0000347
21 arthrogryposis multiplex congenita 31 HP:0002804
22 epicanthus 31 HP:0000286
23 congenital hip dislocation 31 HP:0001374
24 talipes equinovarus 31 HP:0001762
25 kyphoscoliosis 31 HP:0002751
26 overlapping toe 31 HP:0001845
27 down-sloping shoulders 31 HP:0200021
28 cutaneous finger syndactyly 31 HP:0010554
29 bifid uvula 31 HP:0000193
30 single transverse palmar crease 31 HP:0000954
31 submucous cleft hard palate 31 HP:0000176
32 knee flexion contracture 31 HP:0006380
33 short phalanx of finger 31 HP:0009803
34 lumbar hyperlordosis 31 HP:0002938
35 decreased hip abduction 31 HP:0003184
36 camptodactyly of toe 31 HP:0001836
37 thoracolumbar scoliosis 31 HP:0002944
38 distal arthrogryposis 31 HP:0005684
39 ulnar deviation of the hand or of fingers of the hand 31 HP:0001193
40 abnormality of the rib cage 31 HP:0001547

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Neck:
short neck
mild neck webbing

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

Genitourinary Internal Genitalia Male:
cryptorchidism

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

Skeletal Feet:
talipes equinovarus
camptodactyly
overlapping toes

Skeletal Hands:
cutaneous syndactyly
ulnar deviation
single transverse palmar creases
short fingers
camptodactyly of proximal interphalangeal joint
more
Skeletal Limbs:
knee flexion contractures

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

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

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

26
# 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:

45
# 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):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Calcineurin Inhibitors

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Evaluation of the Prevalence of an Hyperactivation of NCC Cotransporter Three Months After Kidney Transplantation in Recipients Treated by Calcineurin Inhibitors Completed NCT03503461
2 Study of Therapeutic Outcomes and Practices in Freeman-Sheldon Syndrome Recruiting NCT01144741

Search NIH Clinical Center for Arthrogryposis, Distal, Type 3

Cochrane evidence based reviews: gordon syndrome

Genetic Tests for Arthrogryposis, Distal, Type 3

Anatomical Context for Arthrogryposis, Distal, Type 3

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

40
Testes, Kidney, Bone, Cerebellum, Heart, Brain, Eye

Publications for Arthrogryposis, Distal, Type 3

Articles related to Arthrogryposis, Distal, Type 3:

(show top 50) (show all 75)
# Title Authors PMID Year
1
Familial Gordon syndrome associated with a PIEZO2 mutation. 61 52 56 6
27714920 2017
2
Mutations in PIEZO2 cause Gordon syndrome, Marden-Walker syndrome, and distal arthrogryposis type 5. 61 56 6
24726473 2014
3
A family with distal arthrogryposis and cleft palate: possible overlap between Gordon syndrome and Aase-Smith syndrome. 61 56 6
11152147 2001
4
Novel mutations in TPM2 and PIEZO2 are responsible for distal arthrogryposis (DA) 2B and mild DA in two Chinese families. 56 6
30285720 2018
5
Arthrogryposis, ophthalmoplegia, and retinopathy: confirmation of a new type of arthrogryposis. 56 6
8423615 1993
6
Distal arthrogryposis with autosomal dominant inheritance and reduced penetrance in females: the Gordon syndrome. 61 56
8370149 1993
7
The Gordon syndrome: autosomal dominant cleft palate, camptodactyly, and club feet. 61 56
7258227 1981
8
The Gordon syndrome. 61 56
7218283 1980
9
Camptodactyly, cleft palate, and club foot (the Gordon syndrome). A report of a large pedigree. 61 56
458832 1979
10
Arthrogryposis: a review and update. 56
19571066 2009
11
A revised and extended classification of the distal arthrogryposes. 56
8923935 1996
12
The distal arthrogryposes: delineation of new entities--review and nosologic discussion. 56
7039311 1982
13
Arthrogryposis multiplex congenita and the Turner phenotype. 56
5025860 1972
14
Camptodactyly, cleft palate, and club foot. A syndrome showing the autosomal-dominant pattern of inheritance. 56
5345097 1969
15
[ON THE CLINICAL ASPECTS OF THE NIELSON SYNDROME]. 56
14335841 1964
16
Renal and brain isoforms of WNK3 have opposite effects on NCCT expression. 54 61
19470686 2009
17
WNK1 affects surface expression of the ROMK potassium channel independent of WNK4. 54 61
16775035 2006
18
Renal tubular transport and the genetic basis of hypertensive disease. 54 61
15980941 2005
19
Associated syndromes in patients with Pierre Robin Sequence. 61
31927149 2019
20
[Does Gordon's syndrome always manifest as hypertension? - a case report of one family]. 61
31812975 2019
21
The Molecular Genetics of Gordon Syndrome. 61
31795491 2019
22
Distal arthrogryposis type 5 and PIEZO2 novel variant in a Canadian family. 61
30938034 2019
23
Mutations in PIEZO2 contribute to Gordon syndrome, Marden-Walker syndrome and distal arthrogryposis: A bioinformatics analysis of mechanisms. 61
30988732 2019
24
Instrumented arthrodesis for non-traumatic craniocervical instability in very young children. 61
29959504 2019
25
Spectrum of renin angiotensin aldosterone system disorders in young hypertensives. 61
30108382 2018
26
Renal sodium and magnesium reabsorption are not coupled in a mouse model of Gordon syndrome. 61
30030908 2018
27
Pseudohypoaldosteronism Type II: A Young Girl Presented with Hypertension, Hyperkalemia and Metabolic Acidosis. 61
29482694 2018
28
Three cases of Gordon syndrome with dominant KLHL3 mutations. 61
28222034 2017
29
[Gordon syndrome: The importance of measuring blood pressure in children]. 61
27369102 2016
30
Gordon Syndrome: a continuing story. 61
25503323 2015
31
Gordon syndrome: literature review and a report of two cases. 61
24878349 2015
32
Molecular insights from dysregulation of the thiazide-sensitive WNK/SPAK/NCC pathway in the kidney: Gordon syndrome and thiazide-induced hyponatraemia. 61
23683032 2013
33
Extrarenal roles of the with-no-lysine[K] kinases (WNKs). 61
23662678 2013
34
A young child with pseudohypoaldosteronism type II by a mutation of Cullin 3. 61
23902721 2013
35
11Beta-hydroxylase deficiency and other syndromes of mineralocorticoid excess as a rare cause of endocrine hypertension. 61
22932914 2012
36
Novel polymorphic AluYb8 insertion in the WNK1 gene is associated with blood pressure variation in Europeans. 61
21520334 2011
37
Familial or genetic primary aldosteronism and Gordon syndrome. 61
21565671 2011
38
A WNK4 gene variant relates to osteoporosis and not to hypertension in the Portuguese population. 61
21236712 2011
39
Hypertension, dietary salt intake, and the role of the thiazide-sensitive sodium chloride transporter NCCT. 61
21167012 2011
40
SPAK and WNK kinases: a new target for blood pressure treatment? 61
21088576 2011
41
Heritable forms of hypertension. 54
17647025 2009
42
Dissecting complex traits: recent advances in hypertension genomics. 54
19439027 2009
43
Crystal structure of domain-swapped STE20 OSR1 kinase domain. 61
19177573 2009
44
[Contribution of monogenic hypertension models to understanding of other hypertensions]. 61
18448411 2008
45
WNK kinases and essential hypertension. 54
18277144 2008
46
Mechanisms of disease: WNK-ing at the mechanism of salt-sensitive hypertension. 54
17957199 2007
47
A young female with Spitzer-Weinstein syndrome diagnosed by thiazide test. 61
17365944 2007
48
Elevated plasma asymmetric dimethyl-L-arginine in a patient with Gordon syndrome. 61
16998213 2007
49
Regulation of the expression of the Na/Cl cotransporter by WNK4 and WNK1: evidence that accelerated dynamin-dependent endocytosis is not involved. 61
16788137 2006
50
Role of with-no-lysine [K] kinases in the pathogenesis of Gordon's syndrome. 54
16683163 2006

Variations for Arthrogryposis, Distal, Type 3

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

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 PIEZO2 NM_022068.3(PIEZO2):c.8238_8245del (p.Trp2746_Glu2749delinsTer)deletion Pathogenic 137628 rs724159993 18:10671538-10671545 18:10671541-10671548
2 PIEZO2 NM_022068.3(PIEZO2):c.8057G>A (p.Arg2686His)SNV Pathogenic 137629 rs587777450 18:10671726-10671726 18:10671729-10671729
3 PIEZO2 NM_022068.3(PIEZO2):c.8153G>A (p.Arg2718Gln)SNV Pathogenic 631524 rs587777452 18:10671630-10671630 18:10671633-10671633
4 PIEZO2 NM_022068.3(PIEZO2):c.6136G>C (p.Glu2046Gln)SNV Uncertain significance 436313 rs200276831 18:10699142-10699142 18:10699144-10699144
5 PIEZO2 NM_022068.3(PIEZO2):c.4073C>T (p.Thr1358Met)SNV Uncertain significance 548506 rs777349822 18:10752653-10752653 18:10752655-10752655

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

73
# Symbol AA change Variation ID SNP ID
1 PIEZO2 p.Arg2686His VAR_071303 rs587777450

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 WNK4 WNK1
2
Show member pathways
10.86 REN NR3C2
3 10.26 WNK4 WNK1 SLC12A3

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

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 WNK4 WNK1
2 potassium channel inhibitor activity GO:0019870 8.62 WNK4 WNK1

Sources for Arthrogryposis, Distal, Type 3

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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