MCID: ERL046
MIFTS: 32

Early-Onset Generalized Dystonia

Categories: Rare diseases, Muscle diseases

Aliases & Classifications for Early-Onset Generalized Dystonia

MalaCards integrated aliases for Early-Onset Generalized Dystonia:

Name: Early-Onset Generalized Dystonia 53
Dystonia 1 53 29 6
Dystonia 1, Torsion, Autosomal Dominant 53 73
Dystonia Musculorum Deformans 1 53 25
Early Onset Torsion Dystonia 53 73
Early-Onset Primary Dystonia 53 25
Oppenheim's Dystonia 53 25
Dyt1 53 25
Early-Onset Generalized Torsion Dystonia 25
Dystonia Musculorum Deformans 73
Idiopathic Torsion Dystonia 53
Idiopathic Dystonia Dyt1 53
Primary Torsion Dystonia 25
Dyt-Tor1a Dystonia 53
Oppenheim Dystonia 25
Eotd 53

Classifications:



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Summaries for Early-Onset Generalized Dystonia

NIH Rare Diseases : 53 Early-onset generalized dystonia is a neurologic movement disorder that usually begins in childhood or adolescence. This is the most common hereditary form of dystonia. Symptoms start in one part of the body (usually an arm, foot, or leg) and are usually first apparent with actions such as writing or walking. With time, the contractions may spread to other parts of the body, causing the muscles to twist the body into unnatural positions. Symptoms can vary greatly, even among members of the same family. For some, the disorder can cause significant disability, while others may experiences only isolated writer’s cramp. A small deletion in the DYT1 gene is the major cause of early-onset dystonia. The genetic change responsible for early onset generalized dystonia is inherited in an autosomal dominant manner, though not everyone who inherits the genetic change will develop the condition. It is thought that only 30% of individuals who inherit the mutation will develop DYT1 dystonia. This is known as reduced penetrance . Treatments include oral medications such as trihexyphenidyl, baclofen, and clonazepam. Botulinum toxin injections may be used in conjunction with oral medications when symptoms are focused in a certain area. In some cases, deep brain stimulation may be indicated.

MalaCards based summary : Early-Onset Generalized Dystonia, also known as dystonia 1, is related to dystonia 1, torsion, autosomal dominant and dystonia 12, and has symptoms including dystonia, myoclonus and torticollis. An important gene associated with Early-Onset Generalized Dystonia is TOR1A (Torsin Family 1 Member A), and among its related pathways/superpathways is Lysine degradation. The drugs Trihexyphenidyl and Cholinergic Agents have been mentioned in the context of this disorder. Affiliated tissues include brain, and related phenotype is nervous system.

Genetics Home Reference : 25 Early-onset primary dystonia is a condition characterized by progressive problems with movement, typically beginning in childhood. Dystonia is a movement disorder that involves involuntary tensing of the muscles (muscle contractions), twisting of specific body parts such as an arm or a leg, rhythmic shaking (tremors), and other uncontrolled movements. A primary dystonia is one that occurs without other neurological symptoms, such as seizures or a loss of intellectual function (dementia). Early-onset primary dystonia does not affect a person's intelligence.

Related Diseases for Early-Onset Generalized Dystonia

Graphical network of the top 20 diseases related to Early-Onset Generalized Dystonia:



Diseases related to Early-Onset Generalized Dystonia

Symptoms & Phenotypes for Early-Onset Generalized Dystonia

UMLS symptoms related to Early-Onset Generalized Dystonia:


dystonia, myoclonus, torticollis, dystonia, paroxysmal, dystonia, limb, tremor

MGI Mouse Phenotypes related to Early-Onset Generalized Dystonia:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 nervous system MP:0003631 9.1 GCDH GCH1 KMT2B PRKRA THAP1 TOR1A

Drugs & Therapeutics for Early-Onset Generalized Dystonia

Drugs for Early-Onset Generalized Dystonia (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 6)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Trihexyphenidyl Approved 58947-95-8, 144-11-6 5572
2 Cholinergic Agents
3 Muscarinic Antagonists
4 Cholinergic Antagonists
5 Neurotransmitter Agents
6 Antiparkinson Agents

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Bilateral Internal Pallidum Stimulation in Primary Generalized Dystonia Unknown status NCT00272246 Phase 2, Phase 3
2 Novel Stimulation Patterns for the Treatment of Dystonia Completed NCT02468843
3 Neuroimaging of Dystonia Completed NCT02046447 Primary Cervical Dystonia (Trihexyphenidyl)

Search NIH Clinical Center for Early-Onset Generalized Dystonia

Genetic Tests for Early-Onset Generalized Dystonia

Genetic tests related to Early-Onset Generalized Dystonia:

# Genetic test Affiliating Genes
1 Dystonia 1 29 TOR1A

Anatomical Context for Early-Onset Generalized Dystonia

MalaCards organs/tissues related to Early-Onset Generalized Dystonia:

41
Brain

Publications for Early-Onset Generalized Dystonia

Articles related to Early-Onset Generalized Dystonia:

(show all 11)
# Title Authors Year
1
Early-onset generalized dystonia starting in the lower extremities in a patient with a novel ANO3 variant. ( 29449182 )
2018
2
New gene implicated in early-onset generalized dystonia: Lysine-specific methyltransferase 2B (KMT2B). ( 28150430 )
2017
3
Haploinsufficiency of KMT2B, Encoding the Lysine-Specific Histone Methyltransferase 2B, Results in Early-Onset Generalized Dystonia. ( 27839873 )
2016
4
PRKRA Mutation Causing Early-Onset Generalized Dystonia-Parkinsonism (DYT16) in an Italian Family. ( 26990861 )
2016
5
Clinical exome sequencing in early-onset generalized dystonia and large-scale resequencing follow-up. ( 27666935 )
2016
6
Exome sequencing identifies GCDH (glutaryl-CoA dehydrogenase) mutations as a cause of a progressive form of early-onset generalized dystonia. ( 21912879 )
2012
7
Concurrence of dystonia 1 and Charcot-Marie-Tooth Neuropathy, type 1 A, in a large family. ( 21412843 )
2011
8
Homozygous THAP1 mutations as cause of early-onset generalized dystonia. ( 21425335 )
2011
9
A molecular link between dystonia 1 and dystonia 6? ( 20976763 )
2010
10
A novel family with an unusual early-onset generalized dystonia. ( 15390042 )
2005
11
TorsinA protein and neuropathology in early onset generalized dystonia with GAG deletion. ( 12609485 )
2003

Variations for Early-Onset Generalized Dystonia

ClinVar genetic disease variations for Early-Onset Generalized Dystonia:

6
(show top 50) (show all 76)
# Gene Variation Type Significance SNP ID Assembly Location
1 TOR1A NM_000113.2(TOR1A): c.907_909delGAG (p.Glu303del) deletion Pathogenic rs80358233 GRCh37 Chromosome 9, 132576341: 132576343
2 TOR1A NM_000113.2(TOR1A): c.907_909delGAG (p.Glu303del) deletion Pathogenic rs80358233 GRCh38 Chromosome 9, 129814062: 129814064
3 TOR1A NM_000113.2(TOR1A): c.646G> C (p.Asp216His) single nucleotide variant protective,risk factor rs1801968 GRCh37 Chromosome 9, 132580901: 132580901
4 TOR1A NM_000113.2(TOR1A): c.646G> C (p.Asp216His) single nucleotide variant protective,risk factor rs1801968 GRCh38 Chromosome 9, 129818622: 129818622
5 TOR1A NM_000113.2(TOR1A): c.863G> A (p.Arg288Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs727502811 GRCh37 Chromosome 9, 132576387: 132576387
6 TOR1A NM_000113.2(TOR1A): c.863G> A (p.Arg288Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs727502811 GRCh38 Chromosome 9, 129814108: 129814108
7 TOR1A NM_000113.2(TOR1A): c.749-11C> A single nucleotide variant Likely benign rs72755217 GRCh37 Chromosome 9, 132576512: 132576512
8 TOR1A NM_000113.2(TOR1A): c.749-11C> A single nucleotide variant Likely benign rs72755217 GRCh38 Chromosome 9, 129814233: 129814233
9 TOR1A NM_000113.2(TOR1A): c.246C> T (p.Ala82=) single nucleotide variant Likely benign rs2296793 GRCh37 Chromosome 9, 132585058: 132585058
10 TOR1A NM_000113.2(TOR1A): c.246C> T (p.Ala82=) single nucleotide variant Likely benign rs2296793 GRCh38 Chromosome 9, 129822779: 129822779
11 TOR1A NM_000113.2(TOR1A): c.581A> T (p.Asp194Val) single nucleotide variant Uncertain significance rs886041099 GRCh38 Chromosome 9, 129818784: 129818784
12 TOR1A NM_000113.2(TOR1A): c.581A> T (p.Asp194Val) single nucleotide variant Uncertain significance rs886041099 GRCh37 Chromosome 9, 132581063: 132581063
13 TOR1A NM_000113.2(TOR1A): c.385G> A (p.Val129Ile) single nucleotide variant Uncertain significance rs529094238 GRCh37 Chromosome 9, 132584919: 132584919
14 TOR1A NM_000113.2(TOR1A): c.385G> A (p.Val129Ile) single nucleotide variant Uncertain significance rs529094238 GRCh38 Chromosome 9, 129822640: 129822640
15 TOR1A NM_000113.2(TOR1A): c.361G> A (p.Glu121Lys) single nucleotide variant Uncertain significance rs199535970 GRCh37 Chromosome 9, 132584943: 132584943
16 TOR1A NM_000113.2(TOR1A): c.361G> A (p.Glu121Lys) single nucleotide variant Uncertain significance rs199535970 GRCh38 Chromosome 9, 129822664: 129822664
17 TOR1A NM_000113.2(TOR1A): c.40_45delGCGCCG (p.Ala14_Pro15del) deletion Uncertain significance rs886041098 GRCh37 Chromosome 9, 132586320: 132586325
18 TOR1A NM_000113.2(TOR1A): c.40_45delGCGCCG (p.Ala14_Pro15del) deletion Uncertain significance rs886041098 GRCh38 Chromosome 9, 129824041: 129824046
19 TOR1A NM_000113.2(TOR1A): c.*824delG deletion Likely benign rs3842225 GRCh37 Chromosome 9, 132575427: 132575427
20 TOR1A NM_000113.2(TOR1A): c.*824delG deletion Likely benign rs3842225 GRCh38 Chromosome 9, 129813148: 129813148
21 TOR1A NM_000113.2(TOR1A): c.*812C> G single nucleotide variant Uncertain significance rs886063519 GRCh37 Chromosome 9, 132575439: 132575439
22 TOR1A NM_000113.2(TOR1A): c.*812C> G single nucleotide variant Uncertain significance rs886063519 GRCh38 Chromosome 9, 129813160: 129813160
23 TOR1A NM_000113.2(TOR1A): c.*623C> T single nucleotide variant Uncertain significance rs886063520 GRCh38 Chromosome 9, 129813349: 129813349
24 TOR1A NM_000113.2(TOR1A): c.*623C> T single nucleotide variant Uncertain significance rs886063520 GRCh37 Chromosome 9, 132575628: 132575628
25 TOR1A NM_000113.2(TOR1A): c.*416T> G single nucleotide variant Likely benign rs186581792 GRCh38 Chromosome 9, 129813556: 129813556
26 TOR1A NM_000113.2(TOR1A): c.*416T> G single nucleotide variant Likely benign rs186581792 GRCh37 Chromosome 9, 132575835: 132575835
27 TOR1A NM_000113.2(TOR1A): c.*415_*416insG insertion Likely benign rs60745320 GRCh38 Chromosome 9, 129813556: 129813557
28 TOR1A NM_000113.2(TOR1A): c.*415_*416insG insertion Likely benign rs60745320 GRCh37 Chromosome 9, 132575835: 132575836
29 TOR1A NM_000113.2(TOR1A): c.*165G> A single nucleotide variant Uncertain significance rs886063523 GRCh37 Chromosome 9, 132576086: 132576086
30 TOR1A NM_000113.2(TOR1A): c.*165G> A single nucleotide variant Uncertain significance rs886063523 GRCh38 Chromosome 9, 129813807: 129813807
31 TOR1A NM_000113.2(TOR1A): c.300G> A (p.Leu100=) single nucleotide variant Uncertain significance rs773480738 GRCh37 Chromosome 9, 132585004: 132585004
32 TOR1A NM_000113.2(TOR1A): c.300G> A (p.Leu100=) single nucleotide variant Uncertain significance rs773480738 GRCh38 Chromosome 9, 129822725: 129822725
33 TOR1A NM_000113.2(TOR1A): c.26G> C (p.Gly9Ala) single nucleotide variant Benign/Likely benign rs200493208 GRCh37 Chromosome 9, 132586339: 132586339
34 TOR1A NM_000113.2(TOR1A): c.26G> C (p.Gly9Ala) single nucleotide variant Benign/Likely benign rs200493208 GRCh38 Chromosome 9, 129824060: 129824060
35 TOR1A NM_000113.2(TOR1A): c.-36C> T single nucleotide variant Likely benign rs28384433 GRCh37 Chromosome 9, 132586400: 132586400
36 TOR1A NM_000113.2(TOR1A): c.-36C> T single nucleotide variant Likely benign rs28384433 GRCh38 Chromosome 9, 129824121: 129824121
37 TOR1A NM_000113.2(TOR1A): c.-52T> G single nucleotide variant Likely benign rs114150156 GRCh37 Chromosome 9, 132586416: 132586416
38 TOR1A NM_000113.2(TOR1A): c.-52T> G single nucleotide variant Likely benign rs114150156 GRCh38 Chromosome 9, 129824137: 129824137
39 TOR1A NM_000113.2(TOR1A): c.*423delT deletion Likely benign rs573629050 GRCh38 Chromosome 9, 129813549: 129813549
40 TOR1A NM_000113.2(TOR1A): c.*423delT deletion Likely benign rs573629050 GRCh37 Chromosome 9, 132575828: 132575828
41 TOR1A NM_000113.2(TOR1A): c.*345C> T single nucleotide variant Uncertain significance rs886063521 GRCh37 Chromosome 9, 132575906: 132575906
42 TOR1A NM_000113.2(TOR1A): c.*345C> T single nucleotide variant Uncertain significance rs886063521 GRCh38 Chromosome 9, 129813627: 129813627
43 TOR1A NM_000113.2(TOR1A): c.*214C> G single nucleotide variant Likely benign rs1183 GRCh37 Chromosome 9, 132576037: 132576037
44 TOR1A NM_000113.2(TOR1A): c.*214C> G single nucleotide variant Likely benign rs1183 GRCh38 Chromosome 9, 129813758: 129813758
45 TOR1A NM_000113.2(TOR1A): c.*149G> A single nucleotide variant Uncertain significance rs886063524 GRCh37 Chromosome 9, 132576102: 132576102
46 TOR1A NM_000113.2(TOR1A): c.*149G> A single nucleotide variant Uncertain significance rs886063524 GRCh38 Chromosome 9, 129813823: 129813823
47 TOR1A NM_000113.2(TOR1A): c.*785G> A single nucleotide variant Uncertain significance rs147959623 GRCh38 Chromosome 9, 129813187: 129813187
48 TOR1A NM_000113.2(TOR1A): c.*1002C> T single nucleotide variant Likely benign rs144267898 GRCh37 Chromosome 9, 132575249: 132575249
49 TOR1A NM_000113.2(TOR1A): c.*1002C> T single nucleotide variant Likely benign rs144267898 GRCh38 Chromosome 9, 129812970: 129812970
50 TOR1A NM_000113.2(TOR1A): c.*934A> G single nucleotide variant Uncertain significance rs760680759 GRCh37 Chromosome 9, 132575317: 132575317

Expression for Early-Onset Generalized Dystonia

Search GEO for disease gene expression data for Early-Onset Generalized Dystonia.

Pathways for Early-Onset Generalized Dystonia

Pathways related to Early-Onset Generalized Dystonia according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.39 GCDH KMT2B

GO Terms for Early-Onset Generalized Dystonia

Sources for Early-Onset Generalized Dystonia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
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74 UMLS via Orphanet
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