EA
MCID: EPS003
MIFTS: 55

Episodic Ataxia (EA) malady

Neuronal diseases category

Summaries for Episodic Ataxia

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21Genetics Home Reference, 42NIH Rare Diseases, 43NINDS, 63Wikipedia, 46OMIM, 32MalaCards
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NINDS:43 Isaac's syndrome (also known as neuromyotonia, Isaac-Mertens syndrome, continuous muscle fiber activity syndrome, and quantal squander syndrome) is a rare neuromuscular disorder caused by hyperexcitability and continuous firing of the peripheral nerve axons that activate muscle fibers. Symptoms, which include progressive muscle stiffness, continuously contracting or twitching muscles (myokymia), cramping, increased sweating, and delayed muscle relaxation, occur even during sleep or when individuals are under general anesthesia. Many people also develop weakened reflexes and muscle pain, but numbness is relatively uncommon. In most people with Isaac's syndrome, stiffness is most prominent in limb and trunk muscles, although symptoms can be limited to cranial muscles. Speech and breathing may be affected if pharyngeal or laryngeal muscles are involved. Onset is between ages 15 and 60, with most individuals experiencing symptoms before age 40. There are hereditary and acquired (occurring from unknown causes) forms of the disorder. The acquired form occasionally develops in association with peripheral neuropathies or after radiation treatment, but more often is caused by an autoimmune condition. Autoimmune-mediated Isaac's syndrome is typically caused by antibodies that bind to potassium channels on the motor nerve. Isaac's syndrome is only one of several neurological conditions that can be caused by potassium channel antibodies.

MalaCards: Episodic Ataxia, also known as neuromyotonia, is related to episodic ataxia type 2 and episodic ataxia type 1. An important gene associated with Episodic Ataxia is CACNA1A (calcium channel, voltage-dependent, P/Q type, alpha 1A subunit), and among its related pathways are Adrenoceptors and Sympathetic Nerve Pathway (Pre- and Post- Ganglionic Junction). The compounds ω-conotoxin mviic and margatoxin have been mentioned in the context of this disorder. Affiliated tissues include skin, brain and eye, and related mouse phenotypes are muscle and behavior/neurological.

Genetics Home Reference:21 Episodic ataxia is a group of related conditions that affect the nervous system and cause problems with movement. People with episodic ataxia have recurrent episodes of poor coordination and balance (ataxia). During these episodes, many people also experience dizziness (vertigo), nausea and vomiting, migraine headaches, blurred or double vision, slurred speech, and ringing in the ears (tinnitus). Seizures, muscle weakness, and paralysis affecting one side of the body (hemiplegia) may also occur during attacks. Additionally, some affected individuals have a muscle abnormality called myokymia during or between episodes. This abnormality can cause muscle cramping, stiffness, and continuous, fine muscle twitching that appears as rippling under the skin.

NIH Rare Diseases:42 Isaac's syndrome is a neuromuscular disease caused by continuous signaling of the end regions of peripheral nerve fibers that activate muscle fibers (motor neurons). age of onset is between ages 15 and 60, with most patients experiencing symptoms before age 40. there are hereditary and acquired forms of the disorder. the acquired form may develop in association with peripheral neuropathies or as an autoimmune condition. last updated: 2/11/2010

Wikipedia:63 Episodic ataxia (EA) is an autosomal dominant disorder characterized by sporadic bouts of ataxia (severe... more...

Description from OMIM:46 108500,612656,160120

Aliases & Classifications for Episodic Ataxia

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8Disease Ontology, 42NIH Rare Diseases, 21Genetics Home Reference, 10DISEASES, 60UMLS, 43NINDS, 48Orphanet, 44Novoseek, 56SNOMED-CT, 46OMIM, 34MeSH, 57SNOMED-CT via Orphanet, 26ICD10 via Orphanet
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Classifications:

Malacards categories (disease lists): (See all malacards categories)
Anatomical: Neuronal diseases


Characteristics (Orphanet epidemiological data):

48
continuous muscle fiber activity syndrome:
Prevalence: <1/1000000; Age of onset: Variable; Age of death: Normal


Aliases & Descriptions:

episodic ataxia 8 42 21 10 60
neuromyotonia 42 43 44
continuous muscle fiber activity syndrome 42 48
quantal squander syndrome 42 48
acquired neuromyotonia 48 60
isaac's syndrome 42 43
isaacs syndrome 8 60
peripheral nerve hyperexcitability 48
isaac's-merten's syndrome 42
episodic ataxia syndrome 42
isaac-mertens syndrome 48
isaac syndrome 48
ea syndrome 42
ea 21


External Ids:

Disease Ontology8 DOID:963
MeSH34 D020386
SNOMED-CT via Orphanet57 80138003
ICD10 via Orphanet26 G71.1

Related Diseases for Episodic Ataxia

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17GeneCards, 18GeneDecks
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Diseases in the Episodic Ataxia Type 1 family:

episodic ataxia Episodic Ataxia Type 2
Episodic Ataxia Type 6 Episodic Ataxia Type 5
Episodic Ataxia, Type 3 Episodic Ataxia, Type 7
Episodic Ataxia Type 4

Diseases related to Episodic Ataxia via text searches within MalaCards or GeneCards/GeneDecks gene sharing:

(show top 50)    (show all 97)
idRelated DiseaseScoreTop Affiliating Genes
1episodic ataxia type 231.3CACNB4, CACNA1A
2episodic ataxia type 131.1KCNA1, CACNA1A
3migraine30.7CACNA1A, ATP1A2, PRRT2, SLC1A3
4spinocerebellar ataxia type 630.5CACNA1A, KCNA1
5spinocerebellar ataxia30.5CACNA1A, KCNA1
6familial hemiplegic migraine30.4CACNA1A, ATP1A2
7neuropathy30.3CACNA1A, KCNA1
8hemiplegia30.3CACNA1A, ATP1A2
9hemiplegic migraine29.9ATP1A2, CACNA1A
10idiopathic generalized epilepsy29.9CACNA1A, KCNA1
11esophagitis10.4
12esophageal atresia10.4
13episodic ataxia type 510.3
14cerebellar ataxia10.3
15episodic ataxia type 610.3
16episodic ataxia with nystagmus10.3
17episodic ataxia, type 310.3
18episodic ataxia, type 710.3
19episodic ataxia type 410.3
20thymoma10.2
21neuromyotonia and axonal neuropathy, autosomal recessive10.2
22coccidiosis10.2
23myasthenia gravis10.2
24subacute sclerosing panencephalitis10.2
25diabetes mellitus10.2
26type 2 diabetes mellitus10.2
27axonal neuropathy10.1
28ocular neuromyotonia10.1
29neuronitis10.1
30hereditary ataxia10.1
31sialadenitis10.1
32epidural abscess10.0
33nasopharyngitis10.0
34thyroiditis10.0
35cramp-fasciculation syndrome10.0
36stiff-person syndrome10.0
37chronic polyneuropathy10.0
38demyelinating polyneuropathy10.0
39encephalitis10.0
40laryngitis10.0
41polyneuropathy10.0
42pseudomyotonia10.0
43alternating hemiplegia of childhood10.0ATP1A2
44benign familial infantile epilepsy10.0ATP1A2
45benign neonatal seizures10.0KCNA2, KCNA1, KCNA6
46migraine without aura10.0ATP1A2, CACNA1A
47epilepsy syndrome10.0ATP1A2, SCN4A, PSMC4, CACNB4, CACNA1A, KCNA1
48cerebritis10.0
49somatization disorder10.0
50erythromelalgia10.0

Graphical network of the top 20 diseases related to Episodic Ataxia:



Diseases related to episodic ataxia

Clinical Features for Episodic Ataxia

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46OMIM
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Clinical features from OMIM:

108500,612656,160120

Drugs & Therapeutics for Episodic Ataxia

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5CenterWatch, 41NIH Clinical Center, 6ClinicalTrials, 60UMLS, 40NDF-RT
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Approved drugs:

Search CenterWatch for Episodic Ataxia

Drug clinical trials:

Search ClinicalTrials for Episodic Ataxia

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Genetic Tests for Episodic Ataxia

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Anatomical Context for Episodic Ataxia

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32MalaCards
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MalaCards organs/tissues related to Episodic Ataxia:

32
Skin, Brain, Eye, Testes

Animal Models for Episodic Ataxia or affiliated genes

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36MGI
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MGI Mouse Phenotypes related to Episodic Ataxia:

36
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053699.6CACNA1A, CACNB4, PDHA1, SCN4A, ATP1A2, KCNA1
2MP:00053868.4SLC1A3, KCNA4, KCNA2, KCNA1, KCNA6, CACNA1A
3MP:00036318.2CACNA1A, KCNA1, KCNA2, KCNA4, CACNA1B, CACNB4

Publications for Episodic Ataxia

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50PubMed
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Articles related to Episodic Ataxia:

(show top 50)    (show all 167)
idTitleAuthorsYear
1
Curable episodic ataxia? History taking versus advanced diagnostic instruments. (24239182)
2014
2
A novel locus for episodic ataxia:UBR4 the likely candidate. (23982692)
2013
3
Episodic blindness and ataxia in a horse with cholesterinic granulomas. (22624528)
2013
4
Possible anticipation associated with a novel splice site mutation in episodic ataxia type 2. (23344743)
2013
5
Sleep benefit in a case of episodic ataxia. (22000943)
2012
6
News on ion channels: erythromelalgia, treatment of episodic ataxia and faciobrachial dystonic seizures. (21847615)
2011
7
Acetazolamide-responsive exercise-induced episodic ataxia associated with a novel homozygous DARS2 mutation. (21749991)
2011
8
Identification of novel and recurrent CACNA1A gene mutations in fifteen patients with episodic ataxia type 2. (20129625)
2010
9
Genetic and functional characterisation of the P/Q calcium channel in episodic ataxia with epilepsy. (20156848)
2010
10
Fluctuating neuromuscular transmission defects and inverse acetazolamide response in episodic ataxia type 2 associated with the novel CaV2.1 single amino acid substitution R2090Q. (20663518)
2010
11
N terminus is key to the dominant negative suppression of Ca(V)2 calcium channels: implications for episodic ataxia type 2. (19903821)
2010
12
Nongenetic factors influence severity of episodic ataxia type 1 in monozygotic twins. (20660867)
2010
13
CACNA1A nonsense mutation is associated with basilar-type migraine and episodic ataxia type 2. (19486177)
2009
14
Late onset hereditary episodic ataxia. (19372292)
2009
15
A novel KCNA1 mutation identified in an Italian family affected by episodic ataxia type 1. (18926884)
2008
16
Benign paroxysmal tonic upgaze, benign paroxysmal torticollis, episodic ataxia and CACNA1A mutation in a family. (18758887)
2008
17
Episodic ataxia and hemiplegia caused by the 8993T->C mitochondrial DNA mutation. (18055910)
2007
18
Aggravation of ataxia due to acetazolamide induced hyperammonaemia in episodic ataxia. (17575025)
2007
19
Episodic Ataxia Type 2 due to a Deletion Mutation in the CACNA1A Gene in a Korean Family. (20396531)
2006
20
Late-onset episodic ataxia type 2 due to an in-frame insertion in CACNA1A. (16186543)
2005
21
A genome-wide screen and linkage mapping for a large pedigree with episodic ataxia. (16009908)
2005
22
CACNA1A mutations causing episodic and progressive ataxia alter channel trafficking and kinetics. (15985579)
2005
23
Dysfunction of the brain calcium channel CaV2.1 in absence epilepsy and episodic ataxia. (15483044)
2004
24
Clinical spectrum of episodic ataxia type 2. (14718690)
2004
25
Deficits in ocular and manual tracking due to episodic ataxia type 2. (15254935)
2004
26
Expanding the phenotype of potassium channelopathy: severe neuromyotonia and skeletal deformities without prominent Episodic Ataxia. (15351427)
2004
27
Treatment of episodic ataxia type 2 with the potassium channel blocker 4-aminopyridine. (15136697)
2004
28
Neurotological findings in a family with episodic ataxia. (12749331)
2003
29
Novel CACNA1A mutation causes febrile episodic ataxia with interictal cerebellar deficits. (14681882)
2003
30
Episodic ataxia type 1 mutations in the human Kv1.1 potassium channel alter hKvbeta 1-induced N-type inactivation. (12077175)
2002
31
Episodic see-saw nystagmus in spino-cerebellar ataxia type 2 (SCA-2). (12879977)
2002
32
Genetics of episodic ataxia. (11968470)
2002
33
Genetics of familial episodic vertigo and ataxia. (11960817)
2002
34
Episodic ataxia type 2]. (15775663)
2001
35
Clinical features of a large Australian pedigree with episodic ataxia type 1. (11746627)
2001
36
Episodic ataxia type-1 mutations in the Kv1.1 potassium channel display distinct folding and intracellular trafficking properties. (11679591)
2001
37
Missense CACNA1A mutation causing episodic ataxia type 2. (11176968)
2001
38
Non familial episodic ataxia possibly associated with the use of nicotine: case report. (11203503)
2000
39
Expression in mammalian cells and electrophysiological characterization of two mutant Kv1.1 channels causing episodic ataxia type 1 (EA-1). (10383630)
1999
40
High prevalence of CACNA1A truncations and broader clinical spectrum in episodic ataxia type 2. (10371528)
1999
41
Episodic ataxia type-1 mutations in the hKv1.1 cytoplasmic pore region alter the gating properties of the channel. (9482717)
1998
42
Spinocerebellar ataxia type 6 with positional vertigo and acetazolamide responsive episodic ataxia. (9771787)
1998
43
De novo mutation in CACNA1A caused acetazolamide-responsive episodic ataxia. (9600739)
1998
44
Three novel KCNA1 mutations in episodic ataxia type I families. (9600245)
1998
45
A study of motor performance and motor learning in episodic ataxia. (9243603)
1997
46
Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4. (8898206)
1996
47
A gene for episodic ataxia/myokymia maps to chromosome 12p13. (7942848)
1994
48
Autosomal dominant episodic ataxia: a heterogeneous syndrome. (3504247)
1986
49
Acetazolamide-responsive episodic ataxia syndrome. (6684259)
1983
50
Joubert syndrome: episodic hyperpnea, abnormal eye movements, retardation and ataxia, associated with dysplasia of the cerebellar vermis. (576733)
1977

Genetic Variations for Episodic Ataxia

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Expression for genes affiliated with Episodic Ataxia

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1BioGPS, 15Gene Expression Omnibus DataSets
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Expression patterns in normal tissues for genes affiliated with Episodic Ataxia

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Pathways for genes affiliated with Episodic Ataxia

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53Reactome, 49PharmGKB, 12EMD Millipore, 51QIAGEN, 29KEGG, 37NCBI BioSystems Database
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Pathways related to Episodic Ataxia according to GeneCards/GeneDecks:

(show all 15)
idSuper pathways (with members indented)ScoreTop Affiliating Genes
1
Hide members
10.2CACNA1B, CACNA1A
210.2CACNA1B, CACNA1A
3
Development Ligand-independent activation of ESR1 and ESR2
Hide members
10.2CACNB4, CACNA1B
410.0CACNA1B, CACNA1A, KCNA1
5
Hide members
10.0CACNA1A, CACNA1B, CACNB4
6
Hide members
10.0CACNA1A, CACNA1B, CACNB4
710.0CACNB4, CACNA1B, CACNA1A
810.0CACNA1A, CACNA1B, CACNB4
910.0CACNA1A, CACNA1B, CACNB4
10
Hide members
9.9SLC1A3, ATP1A2, CACNA1B, CACNA1A
11
Hide members
9.9SCN4A, CACNB4, CACNA1B, CACNA1A
129.8CACNA1A, CACNA1B, CACNB4, PSMC4
13
Hide members
9.5KCND3, KCNA4, KCNA2, KCNA1, KCNA6
149.0KCND3, KCNA4, KCNA2, KCNA1, KCNA6, CACNA1A
15
Hide members
8.9SLC1A3, KCND3, KCNA4, KCNA2, KCNA1, KCNA6

Compounds for genes affiliated with Episodic Ataxia

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28IUPHAR, 59Tocris Bioscience, 11DrugBank, 44Novoseek, 49PharmGKB, 24HMDB
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Compounds related to Episodic Ataxia according to GeneCards/GeneDecks:

(show all 25)
idCompoundScoreTop Affiliating Genes
1ω-conotoxin mviic2810.4CACNA1B, CACNA1A
2margatoxin2810.4KCNA1, KCNA2
3(+-)-bay k 86445910.4CACNA1A, CACNA1B
4nnc 55-0396 dihydrochloride5910.3CACNA1A, CACNA1B
5mibefradil dihydrochloride5910.3CACNA1A, CACNA1B
6omega-conotoxin gvia5910.3CACNA1A, CACNA1B
7Dalfampridine 1110.3KCNA1, KCNA4, KCND3
84-aminopyridine44 2811.3KCND3, KCNA4, CACNA1A
9pregabalin59 44 1112.2CACNA1A, CACNA1B
10mibefradil44 28 1112.2CACNA1B, CACNB4, PSMC4
11α-dendrotoxin2810.2KCNA2, KCNA1, KCNA6
12acetazolamide44 1111.2SCN4A, CACNA1A
13tetraethylammonium44 28 1112.1KCNA1, KCNA6, PSMC4
14verapamil44 49 28 11 2413.9CACNB4, CACNA1B, CACNA1A
15nimodipine44 28 1111.9CACNA1B, CACNB4
16xe 991 dihydrochloride599.8KCND3, KCNA4, KCNA2, KCNA1, KCNA6
17e-4031 dihydrochloride599.8KCNA6, KCNA1, KCNA2, KCNA4, KCND3
18jnj 303599.8KCNA6, KCNA1, KCNA2, KCNA4, KCND3
19shk-dap22599.8KCNA6, KCNA1, KCNA2, KCNA4, KCND3
20ica 110381599.8KCNA6, KCNA1, KCNA2, KCNA4, KCND3
21atp44 2810.7CACNA1B, PDHA1, PSMC4, SCN4A, MT-ATP6, SLC1A3
22glutamate449.6SLC1A3, SLC1A4, ATP1A2, CACNA1B, CACNA1A
23sodium44 2410.3KCNA4, CACNA1A, CACNA1B, PSMC4, SCN4A, ATP1A2
24potassium44 11 2411.0ATP1A2, KCND3, KCNA4, KCNA2, KCNA1, KCNA6
25calcium44 49 11 2411.9KCND3, KCNA4, KCNA1, CACNA1A, CACNA1B, CACNB4

GO Terms for genes affiliated with Episodic Ataxia

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16Gene Ontology
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Cellular components related to Episodic Ataxia according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1synapseGO:04520210.0PRRT2, ATP1A2, CACNB4
2voltage-gated calcium channel complexGO:0058919.9CACNA1A, CACNA1B, CACNB4
3juxtaparanode region of axonGO:0442249.8KCNA1, KCNA2
4dendriteGO:0304259.6KCND3, KCNA1, CACNA1A, CACNA1B, SLC1A4
5voltage-gated potassium channel complexGO:0080769.6KCNA6, KCNA1, KCNA2, KCNA4, KCND3
6neuronal cell bodyGO:0430259.5KCND3, KCNA1, CACNA1A, CACNA1B, SLC1A4, SLC1A3
7plasma membraneGO:0058868.3KCND3, KCNA4, KCNA2, KCNA1, KCNA6, CACNA1A

Biological processes related to Episodic Ataxia according to GeneCards/GeneDecks:

(show all 8)
idNameGO IDScoreTop Affiliating Genes
1gamma-aminobutyric acid signaling pathwayGO:00721410.2CACNB4, CACNA1A
2gamma-aminobutyric acid secretionGO:01405110.1CACNB4, CACNA1A
3membrane depolarizationGO:05189910.1CACNB4, CACNA1B, CACNA1A
4synaptic transmission, glutamatergicGO:0352499.9CACNA1A, CACNB4, SLC1A4
5neurotransmitter uptakeGO:0015049.9SLC1A3, ATP1A2
6protein homooligomerizationGO:0512609.6KCND3, KCNA4, KCNA2, KCNA1, KCNA6
7potassium ion transportGO:0068139.5KCND3, KCNA4, KCNA2, KCNA1, KCNA6, ATP1A2
8synaptic transmissionGO:0072689.0SLC1A3, KCND3, KCNA4, KCNA2, KCNA1, KCNA6

Molecular functions related to Episodic Ataxia according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1sodium:dicarboxylate symporter activityGO:01715310.1SLC1A3, SLC1A4
2voltage-gated calcium channel activityGO:00524510.0CACNA1A, CACNA1B, CACNB4
3high voltage-gated calcium channel activityGO:0083319.9CACNB4, CACNA1A
4voltage-gated potassium channel activityGO:0052499.7KCNA6, KCNA2, KCNA4
5delayed rectifier potassium channel activityGO:0052519.5KCNA6, KCNA1, KCNA2, KCNA4, KCND3

Products for genes affiliated with Episodic Ataxia

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Sources for Episodic Ataxia

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3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
28IUPHAR
29KEGG
34MeSH
35MESH via Orphanet
36MGI
39NCIt
40NDF-RT
43NINDS
44Novoseek
46OMIM
47OMIM via Orphanet
50PubMed
51QIAGEN
57SNOMED-CT via Orphanet
60UMLS
61UMLS via Orphanet