MCID: PRD021
MIFTS: 45

Periodic Paralysis

Categories: Genetic diseases, Metabolic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Periodic Paralysis

MalaCards integrated aliases for Periodic Paralysis:

Name: Periodic Paralysis 58 36 29 54 6 32

Classifications:

Orphanet: 58  
Rare neurological diseases


External Ids:

KEGG 36 H00215
ICD10 32 G72.3
MESH via Orphanet 44 D010245
ICD10 via Orphanet 33 G72.3
UMLS via Orphanet 72 C0030443 C1279412
Orphanet 58 ORPHA206976

Summaries for Periodic Paralysis

KEGG : 36 The periodic paralyses are characterized by episodic muscle weakness often related to potassium levels. They include hyperkalaemic periodic paralysis (HyperPP), hypokalaemic periodic paralysis (HypoPP) and Andersen-Tawil syndrome (ATS) caused by mutations in the calcium-channel, sodium-channel, and potassium-channel genes, respectively.

MalaCards based summary : Periodic Paralysis is related to thyrotoxic periodic paralysis 1 and hypokalemic periodic paralysis, type 2. An important gene associated with Periodic Paralysis is KCNJ2 (Potassium Inwardly Rectifying Channel Subfamily J Member 2), and among its related pathways/superpathways are Cholinergic synapse and Circadian entrainment. The drugs Dichlorphenamide and Hops have been mentioned in the context of this disorder. Affiliated tissues include skeletal muscle, thyroid and testes, and related phenotypes are muscle and respiratory system

Related Diseases for Periodic Paralysis

Diseases in the Periodic Paralysis family:

Familial Periodic Paralysis

Diseases related to Periodic Paralysis via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 257)
# Related Disease Score Top Affiliating Genes
1 thyrotoxic periodic paralysis 1 34.6 KCNJ18 CACNA1S
2 hypokalemic periodic paralysis, type 2 34.3 SCN7A SCN4A
3 normokalemic periodic paralysis 34.0 SCN7A SCN4A
4 hyperkalemic periodic paralysis 33.7 SCN4A KCNJ2 KCNJ18 KCNE3 CACNA1S
5 thyrotoxic periodic paralysis 33.7 KCNJ2 KCNJ18 CACNA1S ATP1A2
6 andersen cardiodysrhythmic periodic paralysis 33.5 SCN4A KCNJ2 KCNJ18 KCNE3 CACNA1S
7 familial periodic paralysis 32.9 SCN4A RYR1 KCNJ2 KCNJ18 KCNE3 CACNA1S
8 hypokalemic periodic paralysis, type 1 32.5 SCN7A SCN4A RYR1 KCNJ2 KCNJ18 KCNE3
9 periodic paralyses 31.9 SCN4A KCNJ2 KCNE3 CACNA1S
10 hypokalemia 31.3 SCN4A KCNJ18 CACNA1S
11 paramyotonia congenita of von eulenburg 31.2 SCN4A KCNJ2 KCNJ18 KCNE3 CACNA1S
12 graves disease 1 31.2 SCN4A KCNJ18 CACNA1S
13 timothy syndrome 30.8 KCNJ2 CACNA1S
14 myotonia congenita 30.1 SCN4A KCNJ2 CACNA1S
15 central core disease of muscle 29.7 RYR1 CACNA1S
16 malignant hyperthermia susceptibility 29.6 SCN4A RYR1 CACNA1S
17 isolated elevated serum creatine phosphokinase levels 29.5 SCN4A RYR1
18 migraine with or without aura 1 29.4 SCN4A CACNA1S ATP1A2
19 episodic ataxia 29.4 SCN4A CACNA1S ATP1A2
20 malignant hyperthermia 29.3 SCN7A SCN4A RYR1 CACNA1S
21 neuromuscular disease 29.1 TBC1D24 SCN4A RYR1 CACNA1S
22 brugada syndrome 28.3 SCN7A SCN4A KCNJ2 KCNE3 CACNA1S
23 congenital myasthenic syndrome 28.0 TBC1D24 SCN4A RYR1 KCNJ2 CACNA1S
24 thyrotoxic periodic paralysis 2 12.9
25 thyrotoxic periodic paralysis 3 12.6
26 periodic paralysis with transient compartment-like syndrome 12.5
27 periodic paralysis with later-onset distal motor neuropathy 12.5
28 familial periodic paralyses 12.1
29 myotonia, potassium-aggravated 12.0
30 myopathy 11.5
31 myopathy - thyrotoxic 11.4
32 wolff-parkinson-white syndrome 11.4
33 hyperthyroidism 10.9
34 graves' disease 10.7
35 myotonia 10.6
36 renal tubular acidosis 10.5
37 quadriplegia 10.4
38 goiter 10.4
39 cardiac arrhythmia 10.3
40 distal renal tubular acidosis 10.3
41 thyroiditis 10.3
42 tremor 10.3
43 respiratory failure 10.3
44 hypothyroidism 10.3
45 hypophosphatemia 10.3
46 myasthenia gravis 10.2
47 sjogren syndrome 10.2
48 adenoma 10.2
49 hyperinsulinism 10.2
50 metabolic acidosis 10.2

Graphical network of the top 20 diseases related to Periodic Paralysis:



Diseases related to Periodic Paralysis

Symptoms & Phenotypes for Periodic Paralysis

MGI Mouse Phenotypes related to Periodic Paralysis:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 muscle MP:0005369 9.35 ATP1A2 CACNA1S KCNJ2 RYR1 SCN4A
2 respiratory system MP:0005388 9.1 ATP1A2 CACNA1S KCNE3 KCNJ2 RYR1 SCN4A

Drugs & Therapeutics for Periodic Paralysis

Drugs for Periodic Paralysis (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 18)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Dichlorphenamide Approved, Investigational Phase 3 120-97-8 3038
2 Hops Approved Phase 3
3
Lamotrigine Approved, Investigational Phase 3 84057-84-1 3878
4 Carbonic Anhydrase Inhibitors Phase 3
5 Sodium Channel Blockers Phase 3
6 Hormones Phase 3
7 Psychotropic Drugs Phase 3
8 Diuretics, Potassium Sparing Phase 3
9 Antipsychotic Agents Phase 3
10 Anticonvulsants Phase 3
11 Calcium, Dietary Phase 3
12 calcium channel blockers Phase 3
13
Calcium Nutraceutical Phase 3 7440-70-2 271
14
Bumetanide Approved Phase 2 28395-03-1 2471
15 Sodium Potassium Chloride Symporter Inhibitors Phase 2
16 diuretics Phase 2
17 Immunoglobulins
18 Antibodies

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Phase III Randomized, Double-Blind, Placebo-Controlled Study of Dichlorphenamide for Periodic Paralyses and Associated Sodium Channel Disorders Completed NCT00004802 Phase 3 dichlorphenamide
2 Dichlorphenamide vs. Placebo for Periodic Paralysis Completed NCT00494507 Phase 3 Dichlorphenamide (double-blind);Placebo (double-blind);Dichlorphenamide (open-label)
3 Lamotrigine as Treatment of Myotonia - a Phase 3 Randomized Controlled Trial Study Completed NCT01939561 Phase 3 Lamotrigine;Placebo
4 A Randomised, Double-blind, Placebo-controlled, Phase II Clinical Trial With a Cross-over Design Assessing Efficacy of a Single Dose of Bumetanide in Reducing Focal Attack Severity in Hypokalaemic Periodic Paralysis Assessed Using the McManis Protocol Terminated NCT02582476 Phase 2 Bumetanide;Placebo
5 Genetic and Morphological Analysis of Thyrotoxic Periodic Paralysis:an Observational Study of Sichuan Individuals in China. Unknown status NCT02287363
6 Genetic Analysis of Thai Patients With Thyrotoxic Periodic Paralysis Completed NCT00443833
7 Andersen-Tawil Syndrome: Genotype-Phenotype Correlation and Longitudinal Study Completed NCT00521794

Search NIH Clinical Center for Periodic Paralysis

Genetic Tests for Periodic Paralysis

Genetic tests related to Periodic Paralysis:

# Genetic test Affiliating Genes
1 Periodic Paralysis 29

Anatomical Context for Periodic Paralysis

MalaCards organs/tissues related to Periodic Paralysis:

40
Skeletal Muscle, Thyroid, Testes, Pituitary, Heart, Brain, Cortex

Publications for Periodic Paralysis

Articles related to Periodic Paralysis:

(show top 50) (show all 2084)
# Title Authors PMID Year
1
Both hypokalaemic and normokalaemic periodic paralysis in different members of a single family with novel R1129Q mutation in SCN4A gene. 61 54
20522878 2010
2
Disruption of the K+ channel beta-subunit KCNE3 reveals an important role in intestinal and tracheal Cl- transport. 54 61
20051516 2010
3
Clinical Diversity of SCN4A-Mutation-Associated Skeletal Muscle Sodium Channelopathy. 61 54
20076800 2009
4
Permanent myopathy caused by mutation of SCN4A Metl592Val: Observation on myogenesis in vitro and on effect of basic fibroblast growth factor on the muscle. 61 54
19290024 2009
5
Exercise test on the patients with normokalaemic periodic paralysis from a Chinese family with a mutation in the SCN4A gene. 54 61
19080124 2008
6
Early onset of hypokalaemic periodic paralysis caused by a novel mutation of the CACNA1S gene. 61 54
18835861 2008
7
Cold-induced defects of sodium channel gating in atypical periodic paralysis plus myotonia. 54 61
17898326 2008
8
Corticosteroid-exacerbated symptoms in an Andersen's syndrome kindred. 61 54
17324964 2007
9
KCNJ2 mutations in arrhythmia patients referred for LQT testing: a mutation T305A with novel effect on rectification properties. 54 61
17341397 2007
10
An andersen-Tawil syndrome mutation in Kir2.1 (V302M) alters the G-loop cytoplasmic K+ conduction pathway. 61 54
17166852 2007
11
The alpha(1S) subunit of the L-type calcium channel is not a predisposition gene for thyrotoxic periodic paralysis. 61 54
17223993 2007
12
Mutations of KCNJ2 gene associated with Andersen-Tawil syndrome in Korean families. 54 61
17211524 2007
13
Hypokalemic paralysis due to Gitelman syndrome: a family study. 61 54
17000984 2006
14
Functional and clinical characterization of a mutation in KCNJ2 associated with Andersen-Tawil syndrome. 61 54
16571646 2006
15
[R1239H mutation of CACNA1S gene in a Chinese family with hypokalaemic periodic paralysis]. 61 54
16767662 2006
16
Trafficking-competent and trafficking-defective KCNJ2 mutations in Andersen syndrome. 54 61
16541386 2006
17
Cellular basis for electrocardiographic and arrhythmic manifestations of Andersen-Tawil syndrome (LQT7). 54 61
16500306 2006
18
[The mutation R672H in SCN4A gene exists in Chinese patients with hypokalaemic periodic paralysis]. 61 54
16681942 2006
19
Phosphorylation and protonation of neighboring MiRP2 sites: function and pathophysiology of MiRP2-Kv3.4 potassium channels in periodic paralysis. 61 54
16449802 2006
20
New mutations of SCN4A cause a potassium-sensitive normokalemic periodic paralysis. 61 54
15596759 2004
21
No mutation in the KCNE3 potassium channel gene in Chinese thyrotoxic hypokalaemic periodic paralysis patients. 54 61
15212652 2004
22
[From gene to diseases; hypokalemic periodic paralysis]. 54 61
15185439 2004
23
Lack of association of the potassium channel-associated peptide MiRP2-R83H variant with periodic paralysis. 54 61
14504341 2003
24
Severe infantile hyperkalaemic periodic paralysis and paramyotonia congenita: broadening the clinical spectrum associated with the T704M mutation in SCN4A. 54 61
12933953 2003
25
Function, subcellular localization and assembly of a novel mutation of KCNJ2 in Andersen's syndrome. 61 54
12689820 2003
26
KCNJ2 mutation results in Andersen syndrome with sex-specific cardiac and skeletal muscle phenotypes. 54 61
12148092 2002
27
Phenotypic variation of a Thr704Met mutation in skeletal sodium channel gene in a family with paralysis periodica paramyotonica. 61 54
11309455 2001
28
MiRP2 forms potassium channels in skeletal muscle with Kv3.4 and is associated with periodic paralysis. 61 54
11207363 2001
29
A sodium channel mutation causing epilepsy in man exhibits subtle defects in fast inactivation and activation in vitro. 54 61
11118488 2000
30
Activation and inactivation of the voltage-gated sodium channel: role of segment S5 revealed by a novel hyperkalaemic periodic paralysis mutation. 54 61
10366610 1999
31
[Periodic hypokalemic paralysis disclosing thyrotoxicosis]. 61 54
9793040 1998
32
Salbutamol treatment in a patient with hyperkalaemic periodic paralysis due to a mutation in the skeletal muscle sodium channel gene (SCN4A). 61 54
9703181 1998
33
The skeletal muscle sodium and chloride channel diseases. 61 54
7735894 1995
34
Potassium channels in hypokalaemic periodic paralysis: a key to the pathogenesis? 61 54
8403805 1993
35
Genomic organization of the human skeletal muscle sodium channel gene. 54 61
8385647 1993
36
Functional expression of sodium channel mutations identified in families with periodic paralysis. 54 61
8382500 1993
37
Novel mutations in families with unusual and variable disorders of the skeletal muscle sodium channel. 61 54
1338909 1992
38
Lower Ca2+ enhances the K+-induced force depression in normal and HyperKPP mouse muscles. 61
32291438 2020
39
A role for external Ca2+ in maintaining muscle contractility in periodic paralysis. 61
32463879 2020
40
Hyperkalemic periodic paralysis aggravated by voltage - gate sodium channel blocker antiepileptic drug? 61
32248037 2020
41
[Clinical and genetic analysis of a patient with Gitelman syndrome misdiagnosed as hypokalemic periodic paralysis]. 61
32472545 2020
42
Sudden Night Palsy in a Young Man: Thyrotoxic Periodic Paralysis as a First Manifestation of Hyperthyroidism. 61
31862328 2020
43
Identification of a novel PYGM mutation in a McArdle disease patient misdiagnosed as hypokalemic periodic paralysis. 61
32100198 2020
44
Electromyographic Features in a Chinese Cohort With Hereditary Skeletal Muscle Channelopathies. 61
31567646 2020
45
Thyrotoxic Periodic Paralysis With Features of Andersen-Tawil Syndrome: A Case Report and Literature Review. 61
32432016 2020
46
Thyrotoxic Periodic Paralysis-A Misleading Challenge in the Emergency Department. 61
32443393 2020
47
Analysis of the genetic background associated with sporadic periodic paralysis in Japanese patients. 61
32234253 2020
48
Further evidence for shared genetic susceptibility in both sporadic and Thyrotoxic periodic paralysis. 61
32229026 2020
49
In vivo assessment of interictal sarcolemmal membrane properties in hypokalaemic and hyperkalaemic periodic paralysis. 61
32066100 2020
50
The expanding phenotype of hypokalemic periodic paralysis in a Japanese family with p.Val876Glu mutation in CACNA1S. 61
32104981 2020

Variations for Periodic Paralysis

ClinVar genetic disease variations for Periodic Paralysis:

6 ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 KCNJ2 NM_000891.2(KCNJ2):c.161G>T (p.Cys54Phe)SNV Pathogenic 30119 rs199473650 17:68171341-68171341 17:70175200-70175200
2 TBC1D24 NM_001199107.2(TBC1D24):c.1079G>T (p.Arg360Leu)SNV Pathogenic 183157 rs765965968 16:2548334-2548334 16:2498333-2498333
3 KCNE3 , LIPT2 NM_005472.4(KCNE3):c.248G>A (p.Arg83His)SNV Conflicting interpretations of pathogenicity 5541 rs17215437 11:74168361-74168361 11:74457316-74457316

Expression for Periodic Paralysis

Search GEO for disease gene expression data for Periodic Paralysis.

Pathways for Periodic Paralysis

Pathways related to Periodic Paralysis according to KEGG:

36
# Name Kegg Source Accession
1 Cholinergic synapse hsa04725

Pathways related to Periodic Paralysis according to GeneCards Suite gene sharing:

(show all 12)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.29 RYR1 KCNJ2 KCNJ18 CACNA1S
2
Show member pathways
12.28 SCN7A SCN4A ATP1A2
3
Show member pathways
12.13 SCN7A CACNA1S ATP1A2
4 11.94 KCNJ2 KCNE3 CACNA1S
5
Show member pathways
11.92 RYR1 KCNJ2 KCNJ18 CACNA1S
6
Show member pathways
11.89 SCN7A SCN4A RYR1 KCNJ2 KCNE3 CACNA1S
7 11.33 KCNJ2 CACNA1S
8 11.23 KCNJ2 KCNE3
9
Show member pathways
11.13 SCN7A SCN4A KCNE3 CACNA1S
10 11.12 RYR1 CACNA1S
11 10.85 SCN7A SCN4A
12 10.34 RYR1 CACNA1S

GO Terms for Periodic Paralysis

Cellular components related to Periodic Paralysis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 membrane GO:0016020 10.02 TBC1D24 SCN7A SCN4A RYR1 KCNJ2 KCNJ18
2 integral component of membrane GO:0016021 9.92 SCN7A SCN4A RYR1 KCNJ2 KCNJ18 KCNE3
3 plasma membrane GO:0005886 9.61 TBC1D24 SCN7A SCN4A RYR1 KCNJ2 KCNJ18
4 intercalated disc GO:0014704 9.43 KCNJ2 ATP1A2
5 smooth endoplasmic reticulum GO:0005790 9.4 RYR1 KCNJ2
6 I band GO:0031674 9.26 RYR1 CACNA1S
7 voltage-gated sodium channel complex GO:0001518 9.16 SCN7A SCN4A
8 T-tubule GO:0030315 8.92 RYR1 KCNJ2 CACNA1S ATP1A2

Biological processes related to Periodic Paralysis according to GeneCards Suite gene sharing:

(show all 22)
# Name GO ID Score Top Affiliating Genes
1 transmembrane transport GO:0055085 9.86 SCN7A SCN4A RYR1 CACNA1S
2 ion transmembrane transport GO:0034220 9.76 SCN7A RYR1 ATP1A2
3 potassium ion transmembrane transport GO:0071805 9.72 KCNJ2 KCNE3 ATP1A2
4 sodium ion transport GO:0006814 9.7 SCN7A SCN4A ATP1A2
5 protein homotetramerization GO:0051289 9.61 RYR1 KCNJ2
6 regulation of cardiac conduction GO:1903779 9.6 RYR1 ATP1A2
7 cardiac conduction GO:0061337 9.59 KCNJ2 CACNA1S
8 regulation of heart rate by cardiac conduction GO:0086091 9.58 KCNJ2 KCNE3
9 neuronal action potential GO:0019228 9.57 SCN7A SCN4A
10 potassium ion transport GO:0006813 9.56 KCNJ2 KCNJ18 KCNE3 ATP1A2
11 membrane depolarization during action potential GO:0086010 9.54 SCN7A SCN4A
12 sodium ion transmembrane transport GO:0035725 9.54 SCN7A SCN4A ATP1A2
13 cellular potassium ion homeostasis GO:0030007 9.51 KCNJ2 ATP1A2
14 potassium ion import across plasma membrane GO:1990573 9.5 KCNJ2 KCNJ18 ATP1A2
15 regulation of cardiac muscle cell contraction GO:0086004 9.49 KCNJ2 ATP1A2
16 membrane depolarization during cardiac muscle cell action potential GO:0086012 9.48 KCNJ2 ATP1A2
17 relaxation of cardiac muscle GO:0055119 9.46 KCNJ2 ATP1A2
18 muscle contraction GO:0006936 9.46 SCN7A SCN4A RYR1 CACNA1S
19 cellular response to caffeine GO:0071313 9.43 RYR1 CACNA1S
20 regulation of ion transmembrane transport GO:0034765 9.43 SCN7A SCN4A KCNJ2 KCNJ18 KCNE3 CACNA1S
21 membrane repolarization during action potential GO:0086011 9.4 KCNJ2 KCNE3
22 ion transport GO:0006811 9.23 SCN7A SCN4A RYR1 KCNJ2 KCNJ18 KCNE3

Molecular functions related to Periodic Paralysis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cation channel activity GO:0005261 9.4 SCN7A SCN4A
2 voltage-gated calcium channel activity GO:0005245 9.37 RYR1 CACNA1S
3 sodium channel activity GO:0005272 9.32 SCN7A SCN4A
4 voltage-gated sodium channel activity GO:0005248 9.26 SCN7A SCN4A
5 ion channel activity GO:0005216 9.26 SCN7A SCN4A RYR1 CACNA1S
6 inward rectifier potassium channel activity GO:0005242 9.16 KCNJ2 KCNJ18
7 voltage-gated ion channel activity GO:0005244 9.1 SCN7A SCN4A KCNJ2 KCNJ18 KCNE3 CACNA1S

Sources for Periodic Paralysis

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
Content
Loading form....