Details of Disease

General Information of Disease (ID: DISC81CM)

Disease Name Arthrogryposis
Synonyms congenital multiple arthrogryposis; Arthrogryposes, congenital multiple; congenital multiple Arthrogryposes
Definition A rare, non-progressive congenital disorder characterized by multiple joint contractures which are present at birth.
Disease Hierarchy
DISD715V: Hereditary neurological disease
DISOJJ2D: Movement disorder
DISC81CM: Arthrogryposis
Disease Identifiers
MONDO ID
MONDO_0008779
UMLS CUI
C0003886
MedGen ID
2455
SNOMED CT ID
111246005

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)
This Disease Is Related to 21 DTT Molecule(s)
Gene Name DTT ID Evidence Level Mode of Inheritance REF
L1CAM TTC9D3K Limited Genetic Variation [1]
CNTN1 TTPR8FK moderate Genetic Variation [2]
ERBB3 TTSINU2 moderate Genetic Variation [3]
FKBP10 TT4P8O2 moderate Genetic Variation [4]
MYH2 TTBIL13 moderate Genetic Variation [5]
PI4KA TTCUS9F moderate Genetic Variation [6]
SLC18A3 TTV8KWS moderate Biomarker [7]
SLC5A7 TTRV7W3 moderate Genetic Variation [8]
TUBB2A TTJ2PTI moderate Genetic Variation [9]
ATP1A2 TT5B6HJ Strong Biomarker [10]
COASY TT4YO0Z Strong Genetic Variation [11]
GBA TT1B5PU Strong Altered Expression [12]
HSPG2 TT5UM29 Strong Biomarker [13]
KIF26B TTQWICZ Strong Genetic Variation [14]
ROR2 TTUDPCI Strong Genetic Variation [15]
RYR1 TTU5CIX Strong Genetic Variation [15]
SCN5A TTZOVE0 Strong Genetic Variation [15]
SMN1 TT8QL6X Strong Genetic Variation [16]
SMPD4 TTZSJIV Strong Biomarker [17]
STMN1 TT7W5OT Strong Genetic Variation [16]
TOR1A TTF85KW Strong Genetic Variation [18]
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⏷ Show the Full List of 21 DTT(s)
This Disease Is Related to 3 DTP Molecule(s)
Gene Name DTP ID Evidence Level Mode of Inheritance REF
ABCA7 DTDVSJA moderate Genetic Variation [19]
SCN1A DTN0M1I Moderate Autosomal dominant [20]
SLC35A3 DTB930Q Strong Genetic Variation [21]
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This Disease Is Related to 48 DOT Molecule(s)
Gene Name DOT ID Evidence Level Mode of Inheritance REF
GFM2 OT51TIMY Limited Biomarker [22]
MYO9A OTE3XHKY Limited Biomarker [23]
SMN2 OT54RLO1 Limited Genetic Variation [16]
PIP OTH719AH Disputed Biomarker [24]
ADCY6 OTFOY4WW moderate Genetic Variation [25]
ADGRG6 OTY2UBXO moderate Genetic Variation [26]
CHRNG OTXC2UR7 moderate Genetic Variation [23]
CPNE8 OTO6U97G moderate Biomarker [27]
DPAGT1 OTYEJAGZ moderate Biomarker [28]
ERCC5 OTQAKFJM moderate Genetic Variation [29]
ERGIC1 OT351FKB moderate Genetic Variation [30]
LGI4 OTZGS8BN moderate Genetic Variation [31]
NAIP OTLA925F moderate Genetic Variation [16]
NEB OT7P9IR3 moderate Biomarker [32]
PDHA1 OTGEU8IK moderate Genetic Variation [33]
PRH1 OTQZ6HX0 moderate Biomarker [34]
SCN1A OTJ9ZTYI Moderate Autosomal dominant [20]
ASCC1 OTH4VAP9 Strong Biomarker [35]
ASPM OTKXQMNA Strong Genetic Variation [15]
ATAD1 OTJ02XFL Strong Genetic Variation [36]
BICD2 OTVJ03NZ Strong Genetic Variation [37]
CNTNAP1 OT5Y03EU Strong Biomarker [38]
COG8 OTDEA7YO Strong Biomarker [39]
DYNC1H1 OTD1KRKO Strong Biomarker [40]
ECEL1 OTJ6GNUP Strong Genetic Variation [41]
EOMES OTB9VQFA Strong Biomarker [42]
FBN2 OT3KYJQL Strong Genetic Variation [43]
FBN3 OTEWLXTH Strong Genetic Variation [23]
FUBP1 OT77SC9N Strong Genetic Variation [44]
GBE1 OTK2N05B Strong Genetic Variation [15]
GLDN OTA8TQU9 Strong Genetic Variation [15]
MAGEL2 OTXEL4R7 Strong Genetic Variation [1]
MYBPC1 OTRPN93S Strong Genetic Variation [45]
MYH3 OTOCCGEB Strong Genetic Variation [46]
MYH8 OT9F350W Strong Genetic Variation [47]
NALCN OTWY7DS0 Strong Genetic Variation [48]
PIEZO2 OTQ7AT38 Strong CausalMutation [15]
RAB14 OTF1J0TB Strong Genetic Variation [44]
RAPSN OTGMSWDQ Strong CausalMutation [15]
SETBP1 OTKGCOSR Strong CausalMutation [15]
SNRPN OTQB1ID1 Strong Genetic Variation [16]
TNNI2 OTGGZFSC Strong Biomarker [49]
TPM2 OTA1L0P8 Strong Genetic Variation [50]
TTN OT0LZ058 Strong Genetic Variation [51]
ERCC6 OT2QZKSF Definitive Biomarker [52]
GLE1 OT0K44H1 Definitive Genetic Variation [53]
SYNE1 OTSBSLUH Definitive Genetic Variation [54]
TNNT3 OT4C498E Definitive Biomarker [55]
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⏷ Show the Full List of 48 DOT(s)

References

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2 Identification of a novel CNTNAP1 mutation causing arthrogryposis multiplex congenita with cerebral and cerebellar atrophy.Eur J Med Genet. 2017 May;60(5):245-249. doi: 10.1016/j.ejmg.2017.02.006. Epub 2017 Feb 27.
3 Lethal congenital contractural syndrome type 2 (LCCS2) is caused by a mutation in ERBB3 (Her3), a modulator of the phosphatidylinositol-3-kinase/Akt pathway. Am J Hum Genet. 2007 Sep;81(3):589-95. doi: 10.1086/520770. Epub 2007 Jul 24.
4 Kuskokwim syndrome, a recessive congenital contracture disorder, extends the phenotype of FKBP10 mutations. Hum Mutat. 2013 Sep;34(9):1279-88. doi: 10.1002/humu.22362. Epub 2013 Jul 8.
5 Adult onset distal and proximal myopathy with complete ophthalmoplegia associated with a novel de novo p.(Leu1877Pro) mutation in MYH2.Clin Genet. 2015 Dec;88(6):573-8. doi: 10.1111/cge.12552. Epub 2015 Jan 20.
6 Germline recessive mutations in PI4KA are associated with perisylvian polymicrogyria, cerebellar hypoplasia and arthrogryposis. Hum Mol Genet. 2015 Jul 1;24(13):3732-41. doi: 10.1093/hmg/ddv117. Epub 2015 Apr 8.
7 SLC18A3 variants lead to fetal akinesia deformation sequence early in pregnancy. Am J Med Genet A. 2019 Jul;179(7):1362-1365. doi: 10.1002/ajmg.a.61186. Epub 2019 May 6.
8 Impaired Presynaptic High-Affinity Choline Transporter Causes a Congenital Myasthenic Syndrome with Episodic Apnea. Am J Hum Genet. 2016 Sep 1;99(3):753-761. doi: 10.1016/j.ajhg.2016.06.033. Epub 2016 Aug 25.
9 De novo pathogenic variant in TUBB2A presenting with arthrogryposis multiplex congenita, brain abnormalities, and severe developmental delay.Am J Med Genet A. 2017 Oct;173(10):2725-2730. doi: 10.1002/ajmg.a.38352. Epub 2017 Aug 25.
10 Biallelic loss of function variants in ATP1A2 cause hydrops fetalis, microcephaly, arthrogryposis and extensive cortical malformations. Eur J Med Genet. 2020 Jan;63(1):103624. doi: 10.1016/j.ejmg.2019.01.014. Epub 2019 Jan 25.
11 Biallelic loss of function variants in COASY cause prenatal onset pontocerebellar hypoplasia, microcephaly, and arthrogryposis. Eur J Hum Genet. 2018 Dec;26(12):1752-1758. doi: 10.1038/s41431-018-0233-0. Epub 2018 Aug 8.
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14 De novo variant in KIF26B is associated with pontocerebellar hypoplasia with infantile spinal muscular atrophy.Am J Med Genet A. 2018 Dec;176(12):2623-2629. doi: 10.1002/ajmg.a.40493. Epub 2018 Aug 27.
15 The genomic and clinical landscape of fetal akinesia.Genet Med. 2020 Mar;22(3):511-523. doi: 10.1038/s41436-019-0680-1. Epub 2019 Nov 4.
16 Large-scale deletions in a Chinese infant associated with a variant form of Werdnig-Hoffmann disease.Neurology. 1998 Sep;51(3):878-9. doi: 10.1212/wnl.51.3.878.
17 Loss of SMPD4 Causes a Developmental Disorder Characterized by Microcephaly and Congenital Arthrogryposis. Am J Hum Genet. 2019 Oct 3;105(4):689-705. doi: 10.1016/j.ajhg.2019.08.006. Epub 2019 Sep 5.
18 Biallelic TOR1A mutations cause severe arthrogryposis: A case requiring reverse phenotyping.Eur J Med Genet. 2019 Sep;62(9):103544. doi: 10.1016/j.ejmg.2018.09.011. Epub 2018 Sep 21.
19 The Genomics of Arthrogryposis, a Complex Trait: Candidate Genes and Further Evidence for Oligogenic Inheritance.Am J Hum Genet. 2019 Jul 3;105(1):132-150. doi: 10.1016/j.ajhg.2019.05.015. Epub 2019 Jun 20.
20 De novo mutations of SCN1A are responsible for arthrogryposis broadening the SCN1A-related phenotypes. J Med Genet. 2021 Nov;58(11):737-742. doi: 10.1136/jmedgenet-2020-107166. Epub 2020 Sep 14.
21 A human case of SLC35A3-related skeletal dysplasia.Am J Med Genet A. 2017 Oct;173(10):2758-2762. doi: 10.1002/ajmg.a.38374. Epub 2017 Aug 4.
22 Compound heterozygous GFM2 mutations with Leigh syndrome complicated by arthrogryposis multiplex congenita.J Hum Genet. 2015 Sep;60(9):509-13. doi: 10.1038/jhg.2015.57. Epub 2015 May 28.
23 Molecular etiology of arthrogryposis in multiple families of mostly Turkish origin. J Clin Invest. 2016 Feb;126(2):762-78. doi: 10.1172/JCI84457. Epub 2016 Jan 11.
24 Lethal contractural syndrome type 3 (LCCS3) is caused by a mutation in PIP5K1C, which encodes PIPKI gamma of the phophatidylinsitol pathway. Am J Hum Genet. 2007 Sep;81(3):530-9. doi: 10.1086/520771. Epub 2007 Jul 24.
25 Mutations in CNTNAP1 and ADCY6 are responsible for severe arthrogryposis multiplex congenita with axoglial defects. Hum Mol Genet. 2014 May 1;23(9):2279-89. doi: 10.1093/hmg/ddt618. Epub 2013 Dec 6.
26 Mutations of GPR126 are responsible for severe arthrogryposis multiplex congenita. Am J Hum Genet. 2015 Jun 4;96(6):955-61. doi: 10.1016/j.ajhg.2015.04.014. Epub 2015 May 21.
27 Radiation hybrid mapping of 18 positional and physiological candidate genes for arthrogryposis multiplex congenita on porcine chromosome 5.Anim Genet. 2006 Jun;37(3):239-44. doi: 10.1111/j.1365-2052.2006.01447.x.
28 Fetal akinesia deformation sequence due to a congenital disorder of glycosylation.Am J Med Genet A. 2015 Oct;167A(10):2411-7. doi: 10.1002/ajmg.a.37184. Epub 2015 May 31.
29 A novel homozygous ERCC5 truncating mutation in a family with prenatal arthrogryposis--further evidence of genotype-phenotype correlation. Am J Med Genet A. 2014 Jul;164A(7):1777-83. doi: 10.1002/ajmg.a.36506. Epub 2014 Apr 3.
30 Mutations in ERGIC1 cause Arthrogryposis multiplex congenita, neuropathic type. Clin Genet. 2018 Jan;93(1):160-163. doi: 10.1111/cge.13018. Epub 2017 Jul 26.
31 A mild phenotype of LGI4-Related arthrogryposis multiplex congenita with intrafamilial variability.Eur J Med Genet. 2020 Mar;63(3):103756. doi: 10.1016/j.ejmg.2019.103756. Epub 2019 Sep 9.
32 Mutations in the NEB gene cause fetal akinesia/arthrogryposis multiplex congenita. Prenat Diagn. 2017 Feb;37(2):144-150. doi: 10.1002/pd.4977. Epub 2017 Jan 25.
33 Massive parallel sequencing identifies RAPSN and PDHA1 mutations causing fetal akinesia deformation sequence.Eur J Paediatr Neurol. 2017 Sep;21(5):745-753. doi: 10.1016/j.ejpn.2017.04.641. Epub 2017 Apr 26.
34 Myosin Binding Protein-C Slow Phosphorylation is Altered in Duchenne Dystrophy and Arthrogryposis Myopathy in Fast-Twitch Skeletal Muscles.Sci Rep. 2015 Aug 19;5:13235. doi: 10.1038/srep13235.
35 Molecular autopsy in maternal-fetal medicine.Genet Med. 2018 Apr;20(4):420-427. doi: 10.1038/gim.2017.111. Epub 2017 Jul 20.
36 A homozygous ATAD1 mutation impairs postsynaptic AMPA receptor trafficking and causes a lethal encephalopathy. Brain. 2018 Mar 1;141(3):651-661. doi: 10.1093/brain/awx377.
37 Arthrogryposis and pterygia as lethal end manifestations of genetically defined congenital myopathies.Am J Med Genet A. 2018 Feb;176(2):359-367. doi: 10.1002/ajmg.a.38577. Epub 2017 Dec 23.
38 Absence of Axoglial Paranodal Junctions in a Child With CNTNAP1 Mutations, Hypomyelination, and Arthrogryposis.J Child Neurol. 2018 Sep;33(10):642-650. doi: 10.1177/0883073818776157. Epub 2018 Jun 8.
39 The first case of antenatal presentation in COG8-congenital disorder of glycosylation with a novel splice site mutation and an extended phenotype.Am J Med Genet A. 2019 Mar;179(3):480-485. doi: 10.1002/ajmg.a.61030. Epub 2019 Jan 28.
40 Expanding the phenotypic spectrum associated with mutations of DYNC1H1. Neuromuscul Disord. 2017 Jul;27(7):607-615. doi: 10.1016/j.nmd.2017.04.011. Epub 2017 May 5.
41 A novel ECEL1 mutation expands the phenotype of distal arthrogryposis multiplex congenita type 5D to include pretibial vertical skin creases.Am J Med Genet A. 2018 Jun;176(6):1405-1410. doi: 10.1002/ajmg.a.38691. Epub 2018 Apr 16.
42 Expression of functional T-cell markers and T-cell receptor Vbeta repertoire in endomyocardial biopsies from patients presenting with acute myocarditis and dilated cardiomyopathy.Eur J Heart Fail. 2011 Jun;13(6):611-8. doi: 10.1093/eurjhf/hfr014. Epub 2011 Mar 19.
43 Exome sequencing reveals blended phenotype of double heterozygous FBN1 and FBN2 variants in a fetus.Eur J Med Genet. 2018 Jul;61(7):399-402. doi: 10.1016/j.ejmg.2018.02.009. Epub 2018 Mar 1.
44 Human aldolase A natural mutants: relationship between flexibility of the C-terminal region and enzyme function.Biochem J. 2004 May 15;380(Pt 1):51-6. doi: 10.1042/BJ20031941.
45 Heterozygous variants in MYBPC1 are associated with an expanded neuromuscular phenotype beyond arthrogryposis.Hum Mutat. 2019 Aug;40(8):1115-1126. doi: 10.1002/humu.23760. Epub 2019 May 5.
46 De novo mutations in NALCN cause a syndrome characterized by congenital contractures of the limbs and face, hypotonia, and developmental delay. Am J Hum Genet. 2015 Mar 5;96(3):462-73. doi: 10.1016/j.ajhg.2015.01.003. Epub 2015 Feb 12.
47 Mutation of perinatal myosin heavy chain associated with a Carney complex variant.N Engl J Med. 2004 Jul 29;351(5):460-9. doi: 10.1056/NEJMoa040584.
48 NALCN channelopathies: Distinguishing gain-of-function and loss-of-function mutations.Neurology. 2016 Sep 13;87(11):1131-9. doi: 10.1212/WNL.0000000000003095. Epub 2016 Aug 24.
49 A novel TNNI2 mutation causes Freeman-Sheldon syndrome in a Chinese family with an affected adult with only facial contractures.Gene. 2013 Sep 25;527(2):630-5. doi: 10.1016/j.gene.2013.06.082. Epub 2013 Jul 11.
50 A novel TPM2 gene splice-site mutation causes severe congenital myopathy with arthrogryposis and dysmorphic features.J Appl Genet. 2017 May;58(2):199-203. doi: 10.1007/s13353-016-0368-z. Epub 2016 Oct 10.
51 Recurrent TTN metatranscript-only c.39974-11T>G splice variant associated with autosomal recessive arthrogryposis multiplex congenita and myopathy.Hum Mutat. 2020 Feb;41(2):403-411. doi: 10.1002/humu.23938. Epub 2019 Dec 3.
52 Cerebro-oculo-facio-skeletal syndrome: three additional cases with CSB mutations, new diagnostic criteria and an approach to investigation.J Med Genet. 2008 Sep;45(9):564-71. doi: 10.1136/jmg.2007.057141. Epub 2008 Jul 15.
53 A homozygous I684T in GLE1 as a novel cause of arthrogryposis and motor neuron loss.Clin Genet. 2018 Jan;93(1):173-177. doi: 10.1111/cge.13086. Epub 2017 Nov 24.
54 Heterogeneity in clinical features and disease severity in ataxia-associated SYNE1 mutations.J Neurol. 2016 Aug;263(8):1503-10. doi: 10.1007/s00415-016-8148-6. Epub 2016 May 13.
55 Skeletal muscle contractile gene (TNNT3, MYH3, TPM2) mutations not found in vertical talus or clubfoot.Clin Orthop Relat Res. 2009 May;467(5):1195-200. doi: 10.1007/s11999-008-0694-5. Epub 2009 Jan 14.