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:

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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
A three-year-old boy with glucose transporter type 1 deficiency syndrome presenting with episodic ataxia. (24200040)
2014
2
Rebound Upbeat Nystagmus After Lateral Gaze in Episodic Ataxia Type 2. (24420976)
2014
3
Clinical, genetic, neurophysiological and functional study of new mutations in episodic ataxia type 1. (23349320)
2013
4
Ion channel disorders: still a fascinating topic--news on episodic ataxia type 1. (23457223)
2013
5
Identification of a novel nonsense mutation p.Tyr1957Ter of CACNA1A in a Chinese family with episodic ataxia 2. (23441182)
2013
6
A novel CACNA1A mutation results in episodic ataxia with migrainous features without headache. (22942164)
2012
7
Episodic ataxias 1 and 2. (21827920)
2012
8
Characterization of the Kv1.1 I262T and S342I mutations associated with episodic ataxia 1 with distinct phenotypes. (22609616)
2012
9
PRRT2 gene mutations: from paroxysmal dyskinesia to episodic ataxia and hemiplegic migraine. (23077024)
2012
10
Episodic ataxia type 1 mutations affect fast inactivation of K+ channels by a reduction in either subunit surface expression or affinity for inactivation domain. (21307345)
2011
11
New mutation of CACNA1A gene in episodic ataxia type 2. (21696515)
2011
12
Link between confusional migraine, hemiplegic migraine and episodic ataxia type 2: hypothesis, family genealogy, gene typing and classification. (19624685)
2010
13
Nerve excitability studies characterize Kv1.1 fast potassium channel dysfunction in patients with episodic ataxia type 1. (21106501)
2010
14
Episodic cerebellar dysfunction in a bichon frise: a canine case of episodic ataxia? (20536690)
2010
15
Large scale calcium channel gene rearrangements in episodic ataxia and hemiplegic migraine: implications for diagnostic testing. (19586927)
2009
16
Late-onset episodic ataxia type 2 associated with a novel loss-of- function mutation in the CACNA1A gene. (19232643)
2009
17
Episodic ataxia type 2: unusual aspects in clinical and genetic presentation. Special emphasis in childhood. (19864665)
2009
18
Newly characterised 5' and 3' regions of CACNA1A gene harbour mutations associated with Familial Hemiplegic Migraine and Episodic Ataxia. (18976783)
2009
19
Mechanisms of vestibulo-ocular reflex (VOR) cancellation in spinocerebellar ataxia type 3 (SCA-3) and episodic ataxia type 2 (EA-2). (18718348)
2008
20
Dominant-negative effects of episodic ataxia type 2 mutations involve disruption of membrane trafficking of human P/Q-type Ca2+ channels. (17654512)
2008
21
PET evidence of cerebellar hypometabolism in a patient with familial episodic ataxia-myokymia syndrome. (18546320)
2008
22
Potassium channel blocker 4-aminopyridine is effective in interictal cerebellar symptoms in episodic ataxia type 2--a video case report. (18442126)
2008
23
Episodic ataxia type 1 mutations in the KCNA1 gene impair the fast inactivation properties of the human potassium channels Kv1.4-1.1/Kvbeta1.1 and Kv1.4-1.1/Kvbeta1.2. (17156368)
2006
24
Dominant-negative effects of human P/Q-type Ca2+ channel mutations associated with episodic ataxia type 2. (16306128)
2006
25
Internuclear ophthalmoparesis in episodic ataxia type 2. (15827025)
2005
26
New calcium channel mutations predict aberrant RNA splicing in episodic ataxia. (16043807)
2005
27
Hereditary paroxysmal ataxia with mental retardation: a clinicopathological study in relation to episodic ataxia type 2. (15300451)
2004
28
Episodic ataxia type 1 with distal weakness: a novel manifestation of a potassium channelopathy. (15127317)
2004
29
Acetazolamide improves neurotological abnormalities in a family with episodic ataxia type 2 (EA-2). (14991363)
2004
30
Novel splice site CACNA1A mutation causing episodic ataxia type 2. (14530926)
2004
31
Episodic ataxia vs somatization disorder. (15633862)
2004
32
A novel mutation in KCNA1 causes episodic ataxia without myokymia. (15532032)
2004
33
An episodic ataxia type-1 mutation in the S1 segment sensitises the hKv1.1 potassium channel to extracellular Zn2+. (15474044)
2004
34
Clusters of non-truncating mutations of P/Q type Ca2+ channel subunit Ca(v)2.1 causing episodic ataxia 2. (15173248)
2004
35
Episodic ataxia type 2. Three novel truncating mutations and one novel missense mutation in the CACNA1A gene. (12420090)
2002
36
Spinocerebellar ataxia type 6 and episodic ataxia type 2 in a Korean family. (11748369)
2001
37
Identification of two novel mutations in the CACNA1A gene responsible for episodic ataxia type 2. (11370629)
2001
38
Magnetic resonance spectroscopy of episodic ataxia type 2 and migraine. (10852558)
2000
39
Identification of a novel missense mutation L329I in the episodic ataxia type 1 gene KCNA1 -- a challenging problem. (11013453)
2000
40
Coding and noncoding variation of the human calcium-channel beta4- subunit gene CACNB4 in patients with idiopathic generalized epilepsy and episodic ataxia. (10762541)
2000
41
A novel nonsense mutation in CACNA1A causes episodic ataxia and hemiplegia. (10408533)
1999
42
CACNA1A mutations: hemiplegic migraine, episodic ataxia type 2, and the others. (10408526)
1999
43
Mutations in the KCNA1 gene associated with episodic ataxia type-1 syndrome impair heteromeric voltage-gated K(+) channel function. (10428758)
1999
44
Episodic ataxia and channelopathies. (9533553)
1998
45
A sporadic case of episodic ataxia with nystagmus (EA-2)]. (9805992)
1998
46
Characterization of three episodic ataxia mutations in the human Kv1.1 potassium channel. (9714564)
1998
47
Episodic ataxia type 1 and 2 (familial periodic ataxia/vertigo). (9390841)
1997
48
Episodic ataxia and myokymia syndrome: a new mutation of potassium channel gene Kv1.1. (8871592)
1996
49
Identification of two new KCNA1 mutations in episodic ataxia/myokymia families. (8541859)
1995
50
Episodic ataxia/myokymia syndrome is associated with point mutations in the human potassium channel gene, KCNA1. (7842011)
1994

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