MCID: EPS003
MIFTS: 54

Episodic Ataxia

Categories: Rare diseases, Neuronal diseases, Genetic diseases

Aliases & Classifications for Episodic Ataxia

MalaCards integrated aliases for Episodic Ataxia:

Name: Episodic Ataxia 12 50 25 29 42 14 69
Acquired Neuromyotonia 50 56 69
Neuromyotonia 50 51 52
Continuous Muscle Fiber Activity Syndrome 50 56
Peripheral Nerve Hyperexcitability 50 56
Quantal Squander Syndrome 50 56
Isaac-Mertens Syndrome 50 56
Isaacs' Syndrome 50 51
Isaacs Syndrome 12 69
Isaac Syndrome 50 56
Isaac's-Merten's Syndrome 50
Episodic Ataxia Syndrome 50
Ea Syndrome 50
Ea 25

Characteristics:

Orphanet epidemiological data:

56
isaac syndrome
Prevalence: <1/1000000 (Worldwide); Age of onset: All ages; Age of death: normal life expectancy;

Classifications:

Orphanet: 56  
Rare neurological diseases


External Ids:

Disease Ontology 12 DOID:963
MeSH 42 C580065
SNOMED-CT 64 421455009
Orphanet 56 ORPHA84142
UMLS via Orphanet 70 C0242287 C0751919
ICD10 via Orphanet 34 G71.1
UMLS 69 C1720189

Summaries for Episodic Ataxia

NINDS : 51 Issacs' syndrome (also known as neuromyotonia, Isaacs-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 Issacs' 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 Issacs' syndrome is typically caused by antibodies that bind to potassium channels on the motor nerve. Issacs' syndrome is only one of several neurological conditions that can be caused by potassium channel antibodies.

MalaCards based summary : Episodic Ataxia, also known as acquired neuromyotonia, is related to episodic ataxia, type 2 and episodic ataxia/myokymia syndrome, and has symptoms including hyperhidrosis, weight loss and eeg abnormality. An important gene associated with Episodic Ataxia is KCNA1 (Potassium Voltage-Gated Channel Subfamily A Member 1), and among its related pathways/superpathways are Transmission across Chemical Synapses and Potassium Channels. The drugs 4-Aminopyridine and Potassium Channel Blockers have been mentioned in the context of this disorder. Affiliated tissues include brain, skin and testes, and related phenotypes are behavior/neurological and mortality/aging

Disease Ontology : 12 A hereditary ataxia characterized by sporadic bouts of ataxia with or without continuous muscle movement.

Genetics Home Reference : 25 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 : 50 episodic ataxia refers to a group of conditions that affect the central nervous system. it affects specific nerve fibers that carry messages to and from the brain in order to control body movement. the condition causes episodes of poor coordination and balance (ataxia). episodes may last from a few seconds to several hours. during an episode, affected people may experience dizziness; nausea; vomiting; migraine headaches; impaired vision; slurred speech; and/or ringing in the ears (tinnitus). an attack may also cause seizures, muscle weakness, and/or paralysis of one side of the body (hemiplegia). age of onset, symptoms and severity can vary. some people have several attacks per day, while others may have one or two per year. episodic ataxia may be caused by a mutation in any of several genes and is inherited in an autosomal dominant manner. in some cases, the genetic cause is unknown. treatment may include medication that reduces or eliminates symptoms. in some cases, symptoms improve or go away on their own. at least 8 types of episodic ataxia have been recognized (referred to as types 1 through 8), which are distinguished based on their age of onset, features, and/or genetic cause.  last updated: 4/21/2016

Wikipedia : 72 Episodic ataxia (EA) is an autosomal dominant disorder characterized by sporadic bouts of ataxia (severe... more...

Related Diseases for Episodic Ataxia

Diseases in the Episodic Ataxia family:

Episodic Ataxia, Type 8 Episodic Ataxia, Type 3
Episodic Ataxia, Type 5 Episodic Ataxia, Type 6
Episodic Ataxia, Type 2 Episodic Ataxia, Type 7
Episodic Ataxia, Type 4

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

(show top 50) (show all 66)
id Related Disease Score Top Affiliating Genes
1 episodic ataxia, type 2 12.5
2 episodic ataxia/myokymia syndrome 12.4
3 episodic ataxia, type 6 12.4
4 neuromyotonia and axonal neuropathy, autosomal recessive 12.3
5 episodic ataxia, type 5 12.2
6 episodic ataxia, type 4 12.1
7 episodic ataxia, type 7 12.0
8 episodic ataxia, type 8 12.0
9 episodic ataxia, type 3 12.0
10 ocular neuromyotonia 12.0
11 esophageal atresia/tracheoesophageal fistula 11.6
12 dystonia 9 11.1
13 paraneoplastic syndromes 11.1
14 familial hemiplegic migraine 11.0
15 cramp-fasciculation syndrome 11.0
16 ataxia 10.7
17 convulsions, familial infantile, with paroxysmal choreoathetosis 10.6
18 autosomal dominant cerebellar ataxia 10.6
19 paroxysmal exertion-induced dyskinesia 10.6
20 hemochromatosis, type 2b 10.6 CACNA1A KCNA1
21 aplasia of lacrimal and salivary glands 10.5 CACNA1A SLC1A3
22 oguchi disease-2 10.5 CACNA1A KCNA1
23 aneurysm 10.3 ATP1A2 CACNA1A
24 epileptic encephalopathy, early infantile, 42 10.3 CACNA1A KCNA1
25 spinocerebellar ataxia 6 10.2 CACNA1A CACNB4 KCNA1
26 mitochondrial neurogastrointestinal encephalomyopathy 10.1 CACNA1A KCNA2
27 epilepsy 10.1
28 acute salpingo-oophoritis 10.0 ATP1A2 CACNA1A SLC1A3
29 alternating hemiplegia of childhood 10.0 ATP1A2 CACNA1A SLC1A3
30 hemiplegic migraine 10.0
31 myopathy-growth delay-intellectual disability-hypospadias syndrome 9.9 ATP1A2 CACNA1A PRRT2
32 ischemic colitis 9.9 ATP1A2 CACNA1A
33 hemolytic uremic syndrome, atypical, childhood 9.9 ATP1A2 CACNA1A PRRT2
34 pelvic inflammatory disease 9.9 ATP1A2 CACNA1A PRRT2
35 hemiplegia 9.8
36 neuronitis 9.8
37 benign focal amyotrophy 9.8 CACNA1A CACNB4 KCNA1 SLC1A3
38 albinism, oculocutaneous, type v 9.8 ATP1A2 CACNA1A PRRT2
39 hypersomnia 9.7 ATP1A2 CACNA1A
40 thymoma 9.7
41 dystonia 9.7
42 headache 9.7
43 gingival disease 9.7 PRRT2 SCN2A
44 myasthenia gravis 9.7
45 ganglioneuroma 9.7
46 amelogenesis imperfecta, type iiib 9.7 KCNAB1 SCN2A
47 epilepsy, generalized, with febrile seizures plus, type 5 9.6 CACNB4 KCNA1 SCN2A
48 bone cancer 9.6 CACNA1A CACNB4 SCN2A
49 suppurative cholangitis 9.6 KCNA2 SCN2A
50 adolescence-adult electroclinical syndrome 9.6 PRRT2 SCN2A

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



Diseases related to Episodic Ataxia

Symptoms & Phenotypes for Episodic Ataxia

Human phenotypes related to Episodic Ataxia:

56 32 (show all 13)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hyperhidrosis 56 32 frequent (33%) Frequent (79-30%) HP:0000975
2 weight loss 56 32 frequent (33%) Frequent (79-30%) HP:0001824
3 eeg abnormality 56 32 frequent (33%) Frequent (79-30%) HP:0002353
4 fasciculations 56 32 frequent (33%) Frequent (79-30%) HP:0002380
5 muscle cramps 56 32 frequent (33%) Frequent (79-30%) HP:0003394
6 muscle stiffness 56 32 frequent (33%) Frequent (79-30%) HP:0003552
7 calf muscle hypertrophy 56 32 frequent (33%) Frequent (79-30%) HP:0008981
8 muscle fibrillation 56 32 frequent (33%) Frequent (79-30%) HP:0010546
9 distal sensory impairment 56 32 occasional (7.5%) Occasional (29-5%) HP:0002936
10 muscle weakness 56 32 very rare (1%) Very rare (<4-1%) HP:0001324
11 myokymia 56 Frequent (79-30%)
12 emg: myokymic discharges 56 Frequent (79-30%)
13 emg 32 frequent (33%) HP:0100288

UMLS symptoms related to Episodic Ataxia:


muscular fasciculation, muscle cramp, muscle rigidity, muscle spasticity, neuralgia, muscle weakness, muscular stiffness, myalgia, myokymia, ataxia, cerebellar ataxia, dysdiadochokinesis, ataxia, truncal, gait ataxia

MGI Mouse Phenotypes related to Episodic Ataxia:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.85 ATP1A2 CACNA1A CACNB4 KCNA1 KCNA2 KCNA4
2 mortality/aging MP:0010768 9.56 ATP1A2 CACNA1A CACNB4 KCNA1 KCNA2 KCNAB1
3 nervous system MP:0003631 9.32 KCNA1 KCNA2 KCNA4 KCNAB1 PRRT2 SCN2A

Drugs & Therapeutics for Episodic Ataxia

Drugs for Episodic Ataxia (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


id Name Status Phase Clinical Trials Cas Number PubChem Id
1
4-Aminopyridine Approved Phase 2 504-24-5 1727
2 Potassium Channel Blockers Phase 2

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 4-Aminopyridine in Episodic Ataxia Type 2 Unknown status NCT01543750 Phase 2 4-Aminopyridine;Placebo
2 Characteristics of Episodic Ataxia Syndrome Unknown status NCT00266760
3 Biomarkers in Autosomal Dominant Cerebellar Ataxia Completed NCT01470729
4 Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford Recruiting NCT01793168

Search NIH Clinical Center for Episodic Ataxia

Cochrane evidence based reviews: episodic ataxia

Genetic Tests for Episodic Ataxia

Genetic tests related to Episodic Ataxia:

id Genetic test Affiliating Genes
1 Episodic Ataxia 29

Anatomical Context for Episodic Ataxia

MalaCards organs/tissues related to Episodic Ataxia:

39
Brain, Skin, Testes

Publications for Episodic Ataxia

Articles related to Episodic Ataxia:

(show top 50) (show all 195)
id Title Authors Year
1
Case report of novel CACNA1A gene mutation causing episodic ataxia type 2. ( 28540055 )
2017
2
Novel missense variant of CACNA1A gene: A case report of a family with episodic ataxia type 2. ( 28431595 )
2017
3
Mutations underlying Episodic Ataxia type-1 antagonize Kv1.1 RNA editing. ( 28216637 )
2017
4
Mutation Spectrum in the CACNA1A Gene in 49 Patients with Episodic Ataxia. ( 28566750 )
2017
5
Characterization of the dominant inheritance mechanism of Episodic Ataxia type 2. ( 28688851 )
2017
6
Ubiquitin Ligase RNF138 Promotes Episodic Ataxia Type 2-Associated Aberrant Degradation of Human Cav2.1 (P/Q-Type) Calcium Channels. ( 28167673 )
2017
7
Novel missense variant of CACNA1A gene in a Slovak family with episodic ataxia type 2. ( 28096552 )
2017
8
Effectiveness of levetiracetam in an acetazolamide-unresponsive patient with episodic ataxia type 2 by a novel CACNA1A nonsense mutation. ( 28643957 )
2017
9
Autoimmune episodic ataxia in patients with anti-CASPR2 antibody-associated encephalitis. ( 28638854 )
2017
10
Mutations in the sodium channel gene SCN2A cause neonatal epilepsy with late-onset episodic ataxia. ( 26645390 )
2016
11
The episodic ataxia type 1 mutation I262T alters voltage-dependent gating and disrupts protein biosynthesis of human Kv1.1 potassium channels. ( 26778656 )
2016
12
Late-onset episodic ataxia associated with SLC1A3 mutation. ( 27829685 )
2016
13
Episodic ataxia associated with a de novo SCN2A mutation. ( 27328862 )
2016
14
Episodic ataxia and SCA6 within the same family due to the D302N CACNA1A gene mutation. ( 27871455 )
2016
15
In vivo impact of presynaptic calcium channel dysfunction on motor axons in episodic ataxia type 2. ( 26912519 )
2016
16
A CaV2.1 N-terminal fragment relieves the dominant-negative inhibition by an Episodic ataxia 2 mutant. ( 27260834 )
2016
17
Episodic ataxia type 2 manifests as epileptiform electroencephalographic activity with no epileptic attacks in two family members. ( 27025991 )
2016
18
Pearls & Oy-sters: Episodic ataxia type 2: Case report and review of the literature. ( 27272039 )
2016
19
Dominant-negative mutation p.Arg324Thr in KCNA1 impairs Kv1.1 channel function in episodic ataxia. ( 27477325 )
2016
20
A novel KCNA1 mutation in a family with episodic ataxia and malignant hyperthermia. ( 27271339 )
2016
21
Dominant KCNA2 mutation causes episodic ataxia and pharmacoresponsive epilepsy. ( 27733563 )
2016
22
Next-generation sequencing identifies novel CACNA1A gene mutations in episodic ataxia type 2. ( 27066515 )
2016
23
Whole-exome sequencing as a diagnostic tool in a family with episodic ataxia type 1. ( 25659636 )
2015
24
Novel frameshift mutation in the CACNA1A gene causing a mixed phenotype of episodic ataxia and familiar hemiplegic migraine. ( 25468264 )
2015
25
A Disease Mutation Causing Episodic Ataxia Type I in the S1 Links Directly to the Voltage Sensor and the Selectivity Filter in Kv Channels. ( 26338330 )
2015
26
New insights into the pathogenesis and therapeutics of episodic ataxia type 1. ( 26347608 )
2015
27
Neuropathology in a case of episodic ataxia type 4. ( 26264377 )
2015
28
A novel frameshift mutation in FGF14 causes an autosomal dominant episodic ataxia. ( 25566820 )
2015
29
Rebound Upbeat Nystagmus After Lateral Gaze in Episodic Ataxia Type 2. ( 24420976 )
2014
30
RNAi silencing of P/Q-type calcium channels in Purkinje neurons of adult mouse leads to episodic ataxia type 2. ( 24768804 )
2014
31
A three-year-old boy with glucose transporter type 1 deficiency syndrome presenting with episodic ataxia. ( 24200040 )
2014
32
Episodic ataxia type 1: clinical characterization, quality of life and genotype-phenotype correlation. ( 24578548 )
2014
33
The first knockin mouse model of episodic ataxia type 2. ( 25109669 )
2014
34
Episodic ataxia type 2: phenotype characteristics of a novel CACNA1A mutation and review of the literature. ( 24658662 )
2014
35
A novel KCNA1 mutation causing episodic ataxia type I. ( 24639406 )
2014
36
Curable episodic ataxia? History taking versus advanced diagnostic instruments. ( 24239182 )
2014
37
Possible anticipation associated with a novel splice site mutation in episodic ataxia type 2. ( 23344743 )
2013
38
Ion channel disorders: still a fascinating topic--news on episodic ataxia type 1. ( 23457223 )
2013
39
A novel locus for episodic ataxia:UBR4 the likely candidate. ( 23982692 )
2013
40
Downward vertical gaze palsy as a prominent manifestation of episodic ataxia type 2: a case report. ( 24665320 )
2013
41
Unilateral pallidal deep brain stimulation in a patient with dystonia secondary to episodic ataxia type 2. ( 23548943 )
2013
42
Episodic ataxia type 1 without episodic ataxia: the diagnostic utility of nerve excitability studies in individuals with KCNA1 mutations. ( 23909822 )
2013
43
Effects of dalfampridine on attacks in patients with episodic ataxia type 2: an observational study. ( 23183922 )
2013
44
Familial episodic ataxia in lambs. ( 22985028 )
2013
45
Clinical, genetic, neurophysiological and functional study of new mutations in episodic ataxia type 1. ( 23349320 )
2013
46
Identification of a novel nonsense mutation p.Tyr1957Ter of CACNA1A in a Chinese family with episodic ataxia 2. ( 23441182 )
2013
47
Homozygous c.649dupC mutation in PRRT2 worsens the BFIS/PKD phenotype with mental retardation, episodic ataxia, and absences. ( 23126439 )
2012
48
Episodic ataxias 1 and 2. ( 21827920 )
2012
49
Sleep benefit in a case of episodic ataxia. ( 22000943 )
2012
50
PRRT2 gene mutations: from paroxysmal dyskinesia to episodic ataxia and hemiplegic migraine. ( 23077024 )
2012

Variations for Episodic Ataxia

ClinVar genetic disease variations for Episodic Ataxia:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 SCN2A NM_021007.2(SCN2A): c.2960G> T (p.Ser987Ile) single nucleotide variant Pathogenic/Likely pathogenic rs796053124 GRCh37 Chromosome 2, 166210742: 166210742

Copy number variations for Episodic Ataxia from CNVD:

7
id CNVD ID Chromosom Start End Type Gene Symbol CNVD Disease
1 125253 19 13166657 13166965 Deletion CACNA1A Episodic ataxia syndrome

Expression for Episodic Ataxia

Search GEO for disease gene expression data for Episodic Ataxia.

Pathways for Episodic Ataxia

GO Terms for Episodic Ataxia

Cellular components related to Episodic Ataxia according to GeneCards Suite gene sharing:

(show all 17)
id Name GO ID Score Top Affiliating Genes
1 integral component of plasma membrane GO:0005887 9.95 KCNA1 KCNA2 KCNA4 SCN2A SLC1A3
2 cell projection GO:0042995 9.83 CACNA1A KCNA1 KCNA2 KCNA4 SLC1A3
3 synapse GO:0045202 9.81 ATP1A2 KCNA1 KCNA2 PRRT2
4 neuronal cell body GO:0043025 9.71 CACNA1A KCNA1 KCNAB1 SLC1A3
5 axon GO:0030424 9.65 KCNA1 KCNA2 KCNA4 KCNAB1 SCN2A
6 perikaryon GO:0043204 9.63 KCNA1 KCNA2 KCNAB1
7 axon terminus GO:0043679 9.57 KCNA1 KCNA2
8 intercalated disc GO:0014704 9.56 ATP1A2 SCN2A
9 T-tubule GO:0030315 9.54 ATP1A2 SCN2A
10 neuron projection GO:0043005 9.54 ATP1A2 KCNA2 SLC1A3
11 voltage-gated calcium channel complex GO:0005891 9.52 CACNA1A CACNB4
12 paranode region of axon GO:0033270 9.48 KCNA1 SCN2A
13 voltage-gated potassium channel complex GO:0008076 9.46 KCNA1 KCNA2 KCNA4 KCNAB1
14 juxtaparanode region of axon GO:0044224 9.13 KCNA1 KCNA2 KCNAB1
15 potassium channel complex GO:0034705 8.8 KCNA1 KCNA2 KCNAB1
16 integral component of membrane GO:0016021 10.15 ATP1A2 CACNA1A KCNA1 KCNA2 KCNA4 KCNAB1
17 plasma membrane GO:0005886 10.02 ATP1A2 CACNA1A CACNB4 KCNA1 KCNA2 KCNA4

Biological processes related to Episodic Ataxia according to GeneCards Suite gene sharing:

(show all 15)
id Name GO ID Score Top Affiliating Genes
1 transport GO:0006810 9.91 ATP1A2 CACNA1A CACNB4 KCNA1 KCNA2 KCNA4
2 chemical synaptic transmission GO:0007268 9.73 CACNA1A CACNB4 KCNA1 SLC1A3
3 potassium ion transport GO:0006813 9.72 ATP1A2 KCNA1 KCNA2 KCNA4 KCNAB1
4 protein homooligomerization GO:0051260 9.71 KCNA1 KCNA2 KCNA4
5 transmembrane transport GO:0055085 9.7 CACNA1A KCNA1 KCNA2 KCNA4 KCNAB1 SCN2A
6 potassium ion transmembrane transport GO:0071805 9.67 KCNA1 KCNA2 KCNA4 KCNAB1
7 ion transport GO:0006811 9.61 ATP1A2 CACNA1A CACNB4 KCNA1 KCNA2 KCNA4
8 neuronal action potential GO:0019228 9.58 KCNA1 KCNA2 SCN2A
9 neuromuscular process controlling balance GO:0050885 9.55 CACNA1A SLC1A3
10 membrane depolarization during action potential GO:0086010 9.52 CACNA1A SCN2A
11 membrane depolarization GO:0051899 9.51 CACNA1A CACNB4
12 neuromuscular process GO:0050905 9.49 CACNA1A KCNA1
13 regulation of muscle contraction GO:0006937 9.48 ATP1A2 KCNA1
14 neurotransmitter uptake GO:0001504 9.46 ATP1A2 SLC1A3
15 regulation of ion transmembrane transport GO:0034765 9.17 CACNA1A CACNB4 KCNA1 KCNA2 KCNA4 KCNAB1

Molecular functions related to Episodic Ataxia according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 ion channel activity GO:0005216 9.5 CACNA1A KCNA1 SCN2A
2 voltage-gated calcium channel activity GO:0005245 9.43 CACNA1A CACNB4
3 delayed rectifier potassium channel activity GO:0005251 9.4 KCNA1 KCNA2
4 potassium ion binding GO:0030955 9.37 ATP1A2 KCNA4
5 potassium channel activity GO:0005267 9.33 KCNA1 KCNA2 KCNA4
6 high voltage-gated calcium channel activity GO:0008331 9.26 CACNA1A CACNB4
7 voltage-gated potassium channel activity GO:0005249 9.26 KCNA1 KCNA2 KCNA4 KCNAB1
8 voltage-gated ion channel activity GO:0005244 9.1 CACNA1A KCNA1 KCNA2 KCNA4 KCNAB1 SCN2A

Sources for Episodic Ataxia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 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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