MCID: ART120
MIFTS: 47

Arthrogryposis, Distal, Type 3

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

Aliases & Classifications for Arthrogryposis, Distal, Type 3

MalaCards integrated aliases for Arthrogryposis, Distal, Type 3:

Name: Arthrogryposis, Distal, Type 3 53
Gordon Syndrome 53 72 49 55 71 51
Arthrogryposis Multiplex Congenita, Distal, Type Iia 53 71 69
Camptodactyly, Cleft Palate, and Clubfoot 53 49 71
Da3 53 49 71
Distal Arthrogryposis Type 3 49 55
Camptodactyly-Cleft Palate-Clubfoot Syndrome 55
Pseudohypoaldosteronism, Type Ii 69
Distal Arthrogryposis Type Iia 55
Arthrogryposis Distal Type 3 49
Arthrogryposis, Distal, 3 71

Characteristics:

Orphanet epidemiological data:

55
gordon syndrome
Inheritance: Autosomal dominant; Age of onset: Antenatal,Neonatal; Age of death: normal life expectancy;

OMIM:

53
Inheritance:
autosomal dominant


HPO:

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


Classifications:



Summaries for Arthrogryposis, Distal, Type 3

OMIM : 53 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 keratoderma, palmoplantar, with nail dystrophy and hereditary motor-sensory neuropathy and keratoderma palmoplantar spastic paralysis, and has symptoms including pectus excavatum, finger syndactyly and high 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 ACE Inhibitor Pathway, Pharmacodynamics. The drugs Dopamine 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

NIH Rare Diseases : 49 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. Last updated: 12/5/2012

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.

Wikipedia : 72 Arthrogryposis multiplex congenital (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 28)
# Related Disease Score Top Affiliating Genes
1 keratoderma, palmoplantar, with nail dystrophy and hereditary motor-sensory neuropathy 11.0
2 keratoderma palmoplantar spastic paralysis 11.0
3 arthrogryposis, distal, type 5 10.9
4 bartter disease 9.9 REN SLC12A3
5 renal hypertension 9.9 REN SLC12A3
6 chondrocalcinosis 9.9 REN SLC12A3
7 bartter syndrome, type 3 9.9 REN SLC12A3
8 mineral metabolism disease 9.8 REN SLC12A3
9 pseudohypoaldosteronism, type i, autosomal dominant 9.8 NR3C2 REN
10 anuria 9.8 NR3C2 REN
11 gitelman syndrome 9.8 REN SLC12A3
12 hyperaldosteronism, familial, type i 9.8 NR3C2 REN
13 pseudohypoaldosteronism, type i, autosomal recessive 9.8 NR3C2 REN
14 adrenal cortex disease 9.8 NR3C2 REN
15 adrenal gland disease 9.8 NR3C2 REN
16 apparent mineralocorticoid excess 9.8 NR3C2 REN
17 endocrine organ benign neoplasm 9.7 NR3C2 REN
18 renal tubular acidosis 9.6 NR3C2 REN
19 liddle syndrome 9.6 NR3C2 REN
20 renal fibrosis 9.5 NR3C2 REN
21 hypokalemia 9.4 NR3C2 REN SLC12A3
22 conn's syndrome 9.4 NR3C2 REN SLC12A3
23 congestive heart failure 9.4 NR3C2 REN
24 renal tubular transport disease 9.3 REN SLC12A3 WNK1 WNK4
25 familial hypertension 9.1 NR3C2 REN WNK1 WNK4
26 pseudohyperkalemia, familial, 2, due to red cell leak 9.1 NR3C2 REN WNK1 WNK4
27 pseudohypoaldosteronism 9.0 NR3C2 SLC12A3 WNK1 WNK4
28 hypertension, essential 8.7 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

Symptoms via clinical synopsis from OMIM:

53
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 Spine:
kyphoscoliosis
thoracolumbar scoliosis
lumbar lordosis

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)

Chest External Features:
pectus excavatum
sloping shoulders

Growth Height:
short stature

Head And Neck Face:
micrognathia
facial asymmetry (mild)

Skeletal Feet:
talipes equinovarus
camptodactyly
overlapping toes

Skeletal Pelvis:
congenital hip dislocation
limited hip abduction

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:

55 31 (show all 38)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 pectus excavatum 55 31 occasional (7.5%) Occasional (29-5%) HP:0000767
2 finger syndactyly 55 31 occasional (7.5%) Occasional (29-5%) HP:0006101
3 high palate 55 31 frequent (33%) Frequent (79-30%) HP:0000218
4 scoliosis 55 31 occasional (7.5%) Occasional (29-5%) HP:0002650
5 hearing impairment 55 31 occasional (7.5%) Occasional (29-5%) HP:0000365
6 short stature 55 31 occasional (7.5%) Occasional (29-5%) HP:0004322
7 decreased muscle mass 55 31 frequent (33%) Frequent (79-30%) HP:0003199
8 cleft palate 55 31 occasional (7.5%) Occasional (29-5%) HP:0000175
9 limitation of joint mobility 55 31 occasional (7.5%) Occasional (29-5%) HP:0001376
10 cryptorchidism 55 31 occasional (7.5%) Occasional (29-5%) HP:0000028
11 clinodactyly of the 5th finger 55 31 occasional (7.5%) Occasional (29-5%) HP:0004209
12 camptodactyly of finger 55 31 hallmark (90%) Very frequent (99-80%) HP:0100490
13 facial asymmetry 55 31 occasional (7.5%) Occasional (29-5%) HP:0000324
14 talipes 55 31 hallmark (90%) Very frequent (99-80%) HP:0001883
15 ophthalmoplegia 31 occasional (7.5%) HP:0000602
16 short neck 31 HP:0000470
17 ptosis 31 HP:0000508
18 micrognathia 31 HP:0000347
19 epicanthus 31 HP:0000286
20 arthrogryposis multiplex congenita 31 HP:0002804
21 talipes equinovarus 31 HP:0001762
22 down-sloping shoulders 31 HP:0200021
23 cutaneous finger syndactyly 31 HP:0010554
24 bifid uvula 31 HP:0000193
25 kyphoscoliosis 31 HP:0002751
26 single transverse palmar crease 31 HP:0000954
27 submucous cleft hard palate 31 HP:0000176
28 congenital hip dislocation 31 HP:0001374
29 short phalanx of finger 31 HP:0009803
30 lumbar hyperlordosis 31 HP:0002938
31 decreased hip abduction 31 HP:0003184
32 knee flexion contracture 31 HP:0006380
33 camptodactyly of toe 31 HP:0001836
34 overlapping toe 31 HP:0001845
35 thoracolumbar scoliosis 31 HP:0002944
36 distal arthrogryposis 31 HP:0005684
37 ulnar deviation of the hand or of fingers of the hand 31 HP:0001193
38 abnormality of the rib cage 31 HP:0001547

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

25
# 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:

43
# 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)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Dopamine Approved Phase 2 51-61-6, 62-31-7 681
2
Cocaine Approved, Illicit Phase 2 50-36-2 446220 5760
3
Buspirone Approved, Investigational Phase 2 36505-84-7 2477
4
Methylphenidate Approved, Investigational Phase 2 20748-11-2, 113-45-1 4158
5 Neurotransmitter Agents Phase 2
6 Peripheral Nervous System Agents Phase 2
7
Serotonin Phase 2 50-67-9 5202
8 Central Nervous System Depressants Phase 2
9 Central Nervous System Stimulants Phase 2
10 Serotonin Agents Phase 2
11 Tranquilizing Agents Phase 2
12 Neurotransmitter Uptake Inhibitors Phase 2
13 Vasoconstrictor Agents Phase 2
14 Anesthetics Phase 2
15 Anesthetics, Local Phase 2
16 Dopamine Agents Phase 2
17 Anti-Anxiety Agents Phase 2
18 Dopamine Uptake Inhibitors Phase 2
19 Psychotropic Drugs Phase 2
20
Adenosine Approved, Investigational 58-61-7 60961
21
Menthol Approved 2216-51-5 16666
22 Analgesics
23 Vasodilator Agents
24 Anti-Arrhythmia Agents

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 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

Anatomical Context for Arthrogryposis, Distal, Type 3

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

38
Cerebellum

Publications for Arthrogryposis, Distal, Type 3

Articles related to Arthrogryposis, Distal, Type 3:

# Title Authors Year
1
Familial Gordon syndrome associated with a PIEZO2 mutation. ( 27714920 )
2017
2
Three cases of Gordon syndrome with dominant KLHL3 mutations. ( 28222034 )
2017
3
Mutations in PIEZO2 cause Gordon syndrome, Marden-Walker syndrome, and distal arthrogryposis type 5. ( 24726473 )
2014
4
Phenotypic and genetic heterogeneity of familial hyperkalaemic hypertension (Gordon syndrome). ( 11903313 )
2001
5
A family with distal arthrogryposis and cleft palate: possible overlap between Gordon syndrome and Aase-Smith syndrome. ( 11152147 )
2001
6
Distal arthrogryposis with autosomal dominant inheritance and reduced penetrance in females: the Gordon syndrome. ( 8370149 )
1993
7
The Gordon syndrome: autosomal dominant cleft palate, camptodactyly, and club feet. ( 7258227 )
1981

Variations for Arthrogryposis, Distal, Type 3

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

71
# 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.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:

# 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 9.46 PIEZO2 SLC12A3 WNK1 WNK4
2 negative regulation of pancreatic juice secretion GO:0090188 8.96 WNK1 WNK4
3 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 8.62 WNK1 WNK4

Sources for Arthrogryposis, Distal, Type 3

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 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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