DA3
MCID: ART120
MIFTS: 50

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 57 40
Gordon Syndrome 57 76 53 59 75 55
Arthrogryposis Multiplex Congenita, Distal, Type Iia 57 75 73
Camptodactyly, Cleft Palate, and Clubfoot 57 53 75
Da3 57 53 75
Distal Arthrogryposis Type 3 53 59
Camptodactyly-Cleft Palate-Clubfoot Syndrome 59
Pseudohypoaldosteronism, Type Ii 73
Distal Arthrogryposis Type Iia 59
Arthrogryposis Distal Type 3 53
Arthrogryposis, Distal, 3 75

Characteristics:

Orphanet epidemiological data:

59
gordon syndrome
Inheritance: Autosomal dominant; Age of onset: Antenatal,Neonatal; Age of death: normal life expectancy;

OMIM:

57
Inheritance:
autosomal dominant


HPO:

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


Classifications:



Summaries for Arthrogryposis, Distal, Type 3

OMIM : 57 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 iid and keratoderma, palmoplantar, with nail dystrophy and hereditary motor-sensory neuropathy. 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 Cocaine and Buspirone have been mentioned in the context of this disorder. Affiliated tissues include kidney, bone and cerebellum, and related phenotypes are pectus excavatum and finger syndactyly

NIH Rare Diseases : 53 Gordon Syndrome is a rare, inherited type of distal arthrogryposis typically characterized by a combination of camptodactyly (a permanent fixation of several fingers in a flexed position), clubfoot (abnormal bending inward of the foot), and less frequently, cleft palate. Intelligence is usually normal. In some cases, additional abnormalities such as scoliosis or undescended testicles in males may be present. The range and severity of symptoms may vary from case to case. Gordon syndrome is thought to be inherited in an autosomal dominant or X-linked dominant manner. The exact cause remains unknown.

UniProtKB/Swiss-Prot : 75 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 : 76 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 pseudohypoaldosteronism, type iid 11.3
2 keratoderma, palmoplantar, with nail dystrophy and hereditary motor-sensory neuropathy 11.2
3 keratoderma palmoplantar spastic paralysis 11.2
4 arthrogryposis, distal, type 5 11.1
5 cleft palate, isolated 10.1
6 distal arthrogryposis 10.1
7 renal hypertension 10.0 SLC12A3 REN
8 bartter disease 10.0 SLC12A3 REN
9 bartter syndrome, type 3 10.0 SLC12A3 REN
10 mineral metabolism disease 9.9 SLC12A3 REN
11 gitelman syndrome 9.9 SLC12A3 REN
12 metabolic acidosis 9.9 WNK4 WNK1
13 pseudohypoaldosteronism, type i, autosomal dominant 9.9 REN NR3C2
14 apparent mineralocorticoid excess 9.9 REN NR3C2
15 anuria 9.9 REN NR3C2
16 hyperaldosteronism, familial, type i 9.9 REN NR3C2
17 pseudohypoaldosteronism, type i, autosomal recessive 9.9 REN NR3C2
18 adrenal cortex disease 9.9 REN NR3C2
19 adrenal gland disease 9.9 REN NR3C2
20 aase-smith syndrome i 9.9
21 marden-walker syndrome 9.9
22 pseudohypoaldosteronism, type iie 9.9
23 dominant cleft palate 9.9
24 hydrocephalus-cleft palate-joint contractures syndrome 9.9
25 cortisone reductase deficiency 9.9 REN NR3C2
26 heart valve disease 9.8 REN NR3C2
27 renal tubular acidosis 9.8 REN NR3C2
28 renal fibrosis 9.8 REN NR3C2
29 congestive heart failure 9.8 REN NR3C2
30 liddle syndrome 1 9.8 WNK4 REN NR3C2
31 hypokalemia 9.7 SLC12A3 REN NR3C2
32 conn's syndrome 9.7 REN NR3C2
33 renal tubular transport disease 9.6 WNK4 WNK1 SLC12A3 REN
34 familial hypertension 9.6 WNK4 WNK1 REN NR3C2
35 pseudohyperkalemia, familial, 2, due to red cell leak 9.6 WNK4 WNK1 REN NR3C2
36 pseudohypoaldosteronism 9.3 WNK4 WNK1 SLC12A3 REN NR3C2
37 hypertension, essential 9.3 WNK4 WNK1 SLC12A3 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

Symptoms via clinical synopsis from OMIM:

57
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

Human phenotypes related to Arthrogryposis, Distal, Type 3:

59 32 (show all 40)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 pectus excavatum 59 32 occasional (7.5%) Occasional (29-5%) HP:0000767
2 finger syndactyly 59 32 occasional (7.5%) Occasional (29-5%) HP:0006101
3 high palate 59 32 frequent (33%) Frequent (79-30%) HP:0000218
4 scoliosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0002650
5 hearing impairment 59 32 occasional (7.5%) Occasional (29-5%) HP:0000365
6 short stature 59 32 occasional (7.5%) Occasional (29-5%) HP:0004322
7 decreased muscle mass 59 32 frequent (33%) Frequent (79-30%) HP:0003199
8 cleft palate 59 32 occasional (7.5%) Occasional (29-5%) HP:0000175
9 limitation of joint mobility 59 32 occasional (7.5%) Occasional (29-5%) HP:0001376
10 cryptorchidism 59 32 occasional (7.5%) Occasional (29-5%) HP:0000028
11 clinodactyly of the 5th finger 59 32 occasional (7.5%) Occasional (29-5%) HP:0004209
12 camptodactyly of finger 59 32 hallmark (90%) Very frequent (99-80%) HP:0100490
13 facial asymmetry 59 32 occasional (7.5%) Occasional (29-5%) HP:0000324
14 talipes 59 32 hallmark (90%) Very frequent (99-80%) HP:0001883
15 short neck 32 HP:0000470
16 ptosis 32 HP:0000508
17 global developmental delay 32 very rare (1%) HP:0001263
18 intellectual disability, mild 32 very rare (1%) HP:0001256
19 micrognathia 32 HP:0000347
20 epicanthus 32 HP:0000286
21 arthrogryposis multiplex congenita 32 HP:0002804
22 congenital hip dislocation 32 HP:0001374
23 talipes equinovarus 32 HP:0001762
24 down-sloping shoulders 32 HP:0200021
25 cutaneous finger syndactyly 32 HP:0010554
26 bifid uvula 32 HP:0000193
27 ophthalmoplegia 32 occasional (7.5%) HP:0000602
28 kyphoscoliosis 32 HP:0002751
29 single transverse palmar crease 32 HP:0000954
30 submucous cleft hard palate 32 HP:0000176
31 knee flexion contracture 32 HP:0006380
32 short phalanx of finger 32 HP:0009803
33 lumbar hyperlordosis 32 HP:0002938
34 decreased hip abduction 32 HP:0003184
35 camptodactyly of toe 32 HP:0001836
36 overlapping toe 32 HP:0001845
37 thoracolumbar scoliosis 32 HP:0002944
38 distal arthrogryposis 32 HP:0005684
39 ulnar deviation of the hand or of fingers of the hand 32 HP:0001193
40 abnormality of the rib cage 32 HP:0001547

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:

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

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

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:

41
Kidney, Bone, Cerebellum, Cortex, Heart, Eye, Adrenal Gland

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
Familial hyperkalemic hypertension (Gordon syndrome): evidence for phenotypic variability in a study of 7 families. ( 11692471 )
2001
13
Phenotypic and genetic heterogeneity of familial hyperkalaemic hypertension (Gordon syndrome). ( 11903313 )
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:

75
# 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 ExPASy
19 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
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44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
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51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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