MCID: PRD021
MIFTS: 47

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 59 37 29 55 6 33

Classifications:

Orphanet: 59  
Rare neurological diseases


External Ids:

KEGG 37 H00215
ICD10 33 G72.3
MESH via Orphanet 45 D010245
ICD10 via Orphanet 34 G72.3
UMLS via Orphanet 73 C0030443 C1279412
Orphanet 59 ORPHA206976

Summaries for Periodic Paralysis

KEGG : 37
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 andersen cardiodysrhythmic periodic paralysis. 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 Neuropathic Pain-Signaling in Dorsal Horn Neurons. 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 cardiovascular system and homeostasis/metabolism

Wikipedia : 75 Periodic paralysis is a group of rare genetic diseases that lead to weakness or paralysis from common... more...

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 235)
# Related Disease Score Top Affiliating Genes
1 thyrotoxic periodic paralysis 1 34.7 KCNJ18 CACNA1S
2 andersen cardiodysrhythmic periodic paralysis 34.4 SCN4A KCNJ2 CACNA1S
3 hyperkalemic periodic paralysis 34.0 SCN4A KCNJ2 KCNE3 CACNA1S
4 thyrotoxic periodic paralysis 33.5 KCNJ2 KCNJ18 CACNA1S ATP1A2
5 hypokalemic periodic paralysis, type 1 33.3 SCN4A RYR1 KCNJ2 KCNE3 CACNA1S
6 familial periodic paralysis 33.1 SCN4A RYR1 KCNJ2 KCNE3 CACNA1S
7 periodic paralyses 31.8 SCN4A KCNJ2 KCNE3 CACNA1S
8 hypokalemia 31.2 SLC12A3 CACNA1S
9 myotonia congenita 30.4 SCN4A CACNA1S
10 neuromuscular disease 30.2 SCN4A RYR1
11 malignant hyperthermia 30.0 SCN4A RYR1 CACNA1S
12 malignant hyperthermia susceptibility 29.6 SCN4A RYR1 CACNA1S
13 muscular disease 29.4 SCN4A RYR1 CACNA1S
14 thyrotoxic periodic paralysis 2 12.8
15 hypokalemic periodic paralysis, type 2 12.8
16 normokalemic periodic paralysis 12.6
17 thyrotoxic periodic paralysis 3 12.6
18 periodic paralysis with transient compartment-like syndrome 12.5
19 periodic paralysis with later-onset distal motor neuropathy 12.5
20 familial periodic paralyses 12.1
21 myotonia, potassium-aggravated 12.0
22 myopathy 11.5
23 paramyotonia congenita of von eulenburg 11.5
24 myopathy - thyrotoxic 11.4
25 wolff-parkinson-white syndrome 11.4
26 hyperthyroidism 10.9
27 graves disease 1 10.8
28 graves' disease 10.7
29 myotonia 10.6
30 renal tubular acidosis 10.5
31 timothy syndrome 10.4
32 quadriplegia 10.4
33 goiter 10.4
34 cardiac arrhythmia 10.3
35 distal renal tubular acidosis 10.3
36 locked-in syndrome 10.3
37 tremor 10.3
38 thyroiditis 10.3
39 hypophosphatemia 10.3
40 respiratory failure 10.3
41 hypothyroidism 10.3
42 myasthenia gravis 10.2
43 hyperinsulinism 10.2
44 adenoma 10.2
45 metal metabolism disorder 10.2 SCN4A CACNA1S
46 sjogren syndrome 10.2
47 metabolic acidosis 10.2
48 malignant hyperthermia of anesthesia 10.2 RYR1 CACNA1S
49 myopathy, congenital, bailey-bloch 10.1 RYR1 CACNA1S
50 central core myopathy 10.1 RYR1 CACNA1S

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:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.73 ATP1A2 CACNA1S KCNE3 KCNJ2 RYR1 SLC12A3
2 homeostasis/metabolism MP:0005376 9.7 ATP1A2 CACNA1S KCNE3 KCNJ2 RYR1 SCN4A
3 muscle MP:0005369 9.35 ATP1A2 CACNA1S KCNJ2 RYR1 SCN4A
4 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 21)
# 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
Calcium Approved, Nutraceutical Phase 3 7440-70-2 271
5 Carbonic Anhydrase Inhibitors Phase 3
6 Tranquilizing Agents Phase 3
7 Hormones Phase 3
8 Central Nervous System Depressants Phase 3
9 Sodium Channel Blockers Phase 3
10 Diuretics, Potassium Sparing Phase 3
11 Antipsychotic Agents Phase 3
12 Psychotropic Drugs Phase 3
13 Calcium, Dietary Phase 3
14 Anticonvulsants Phase 3
15 calcium channel blockers Phase 3
16
Bumetanide Approved Phase 2 28395-03-1 2471
17 Natriuretic Agents Phase 2
18 Sodium Potassium Chloride Symporter Inhibitors Phase 2
19 diuretics Phase 2
20 Antibodies
21 Immunoglobulins

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:

41
Skeletal Muscle, Thyroid, Testes, Pituitary, Heart, Brain, Cortex

Publications for Periodic Paralysis

Articles related to Periodic Paralysis:

(show top 50) (show all 2028)
# 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. 9 38
20522878 2010
2
Disruption of the K+ channel beta-subunit KCNE3 reveals an important role in intestinal and tracheal Cl- transport. 9 38
20051516 2010
3
Clinical Diversity of SCN4A-Mutation-Associated Skeletal Muscle Sodium Channelopathy. 9 38
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. 9 38
19290024 2009
5
Exercise test on the patients with normokalaemic periodic paralysis from a Chinese family with a mutation in the SCN4A gene. 9 38
19080124 2008
6
Early onset of hypokalaemic periodic paralysis caused by a novel mutation of the CACNA1S gene. 9 38
18835861 2008
7
Cold-induced defects of sodium channel gating in atypical periodic paralysis plus myotonia. 9 38
17898326 2008
8
Corticosteroid-exacerbated symptoms in an Andersen's syndrome kindred. 9 38
17324964 2007
9
KCNJ2 mutations in arrhythmia patients referred for LQT testing: a mutation T305A with novel effect on rectification properties. 9 38
17341397 2007
10
The alpha(1S) subunit of the L-type calcium channel is not a predisposition gene for thyrotoxic periodic paralysis. 9 38
17223993 2007
11
An andersen-Tawil syndrome mutation in Kir2.1 (V302M) alters the G-loop cytoplasmic K+ conduction pathway. 9 38
17166852 2007
12
Mutations of KCNJ2 gene associated with Andersen-Tawil syndrome in Korean families. 9 38
17211524 2007
13
Hypokalemic paralysis due to Gitelman syndrome: a family study. 9 38
17000984 2006
14
Functional and clinical characterization of a mutation in KCNJ2 associated with Andersen-Tawil syndrome. 9 38
16571646 2006
15
[R1239H mutation of CACNA1S gene in a Chinese family with hypokalaemic periodic paralysis]. 9 38
16767662 2006
16
Trafficking-competent and trafficking-defective KCNJ2 mutations in Andersen syndrome. 9 38
16541386 2006
17
[The mutation R672H in SCN4A gene exists in Chinese patients with hypokalaemic periodic paralysis]. 9 38
16681942 2006
18
Cellular basis for electrocardiographic and arrhythmic manifestations of Andersen-Tawil syndrome (LQT7). 9 38
16500306 2006
19
Phosphorylation and protonation of neighboring MiRP2 sites: function and pathophysiology of MiRP2-Kv3.4 potassium channels in periodic paralysis. 9 38
16449802 2006
20
New mutations of SCN4A cause a potassium-sensitive normokalemic periodic paralysis. 9 38
15596759 2004
21
No mutation in the KCNE3 potassium channel gene in Chinese thyrotoxic hypokalaemic periodic paralysis patients. 9 38
15212652 2004
22
[From gene to diseases; hypokalemic periodic paralysis]. 9 38
15185439 2004
23
Severe infantile hyperkalaemic periodic paralysis and paramyotonia congenita: broadening the clinical spectrum associated with the T704M mutation in SCN4A. 9 38
12933953 2003
24
Lack of association of the potassium channel-associated peptide MiRP2-R83H variant with periodic paralysis. 9 38
14504341 2003
25
Function, subcellular localization and assembly of a novel mutation of KCNJ2 in Andersen's syndrome. 9 38
12689820 2003
26
KCNJ2 mutation results in Andersen syndrome with sex-specific cardiac and skeletal muscle phenotypes. 9 38
12148092 2002
27
Phenotypic variation of a Thr704Met mutation in skeletal sodium channel gene in a family with paralysis periodica paramyotonica. 9 38
11309455 2001
28
MiRP2 forms potassium channels in skeletal muscle with Kv3.4 and is associated with periodic paralysis. 9 38
11207363 2001
29
A sodium channel mutation causing epilepsy in man exhibits subtle defects in fast inactivation and activation in vitro. 9 38
11118488 2000
30
Activation and inactivation of the voltage-gated sodium channel: role of segment S5 revealed by a novel hyperkalaemic periodic paralysis mutation. 9 38
10366610 1999
31
[Periodic hypokalemic paralysis disclosing thyrotoxicosis]. 9 38
9793040 1998
32
Salbutamol treatment in a patient with hyperkalaemic periodic paralysis due to a mutation in the skeletal muscle sodium channel gene (SCN4A). 9 38
9703181 1998
33
The skeletal muscle sodium and chloride channel diseases. 9 38
7735894 1995
34
Potassium channels in hypokalaemic periodic paralysis: a key to the pathogenesis? 9 38
8403805 1993
35
Genomic organization of the human skeletal muscle sodium channel gene. 9 38
8385647 1993
36
Functional expression of sodium channel mutations identified in families with periodic paralysis. 9 38
8382500 1993
37
Novel mutations in families with unusual and variable disorders of the skeletal muscle sodium channel. 9 38
1338909 1992
38
Overlap of periodic paralysis and paramyotonia congenita caused by SCN4A gene mutations two family reports and literature review. 38
30931713 2019
39
Family with primary periodic paralysis and a mutation in MCM3AP, a gene implicated in mRNA transport. 38
31241196 2019
40
A Case of Thiazide-induced Hypokalemic Paralysis. 38
31403094 2019
41
[Analysis of SCN4A gene variation in a Chinese pedigree affected with skeletal muscle sodium channelopathies]. 38
31400134 2019
42
Familial hypokalemic periodic paralysis in pregnancy: A case report. 38
31215737 2019
43
Hypokalemic periodic paralysis due to CACNA1S gene mutation. 38
31380823 2019
44
Usefulness of the intravenous flecainide challenge test before oral flecainide treatment in a patient with Andersen-Tawil syndrome. 38
31311787 2019
45
Strength and muscle structure preserved during long-term therapy in a patient with hypokalemic periodic paralysis (Cav1.1-R1239G). 38
30937521 2019
46
Contribution of Asian haplotype of KCNJ18 to susceptibility to and ethnic differences in thyrotoxic periodic paralysis. 38
31361309 2019
47
Thyrotoxic hypokalemic periodic paralysis due to Graves' disease in 2 adolescents. 38
31261479 2019
48
Delayed diagnosed atypical case of Andersen-Tawil syndrome. 38
31281605 2019
49
[Hypokalemic Paresis in Adolescent: A Case Report]. 38
31166901 2019
50
Assessment of Molecular Subtypes in Thyrotoxic Periodic Paralysis and Graves Disease Among Chinese Han Adults: A Population-Based Genome-Wide Association Study. 38
31050781 2019

Variations for Periodic Paralysis

ClinVar genetic disease variations for Periodic Paralysis:

6
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 KCNJ2 NM_000891.2(KCNJ2): c.161G> T (p.Cys54Phe) single nucleotide variant Pathogenic rs199473650 17:68171341-68171341 17:70175200-70175200
2 TBC1D24 NM_001199107.2(TBC1D24): c.1079G> T (p.Arg360Leu) single nucleotide variant Pathogenic rs765965968 16:2548334-2548334 16:2498333-2498333
3 KCNE3 NM_005472.4(KCNE3): c.248G> A (p.Arg83His) single nucleotide variant Conflicting interpretations of pathogenicity 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:

37
# Name Kegg Source Accession
1 Cholinergic synapse hsa04725

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 integral component of membrane GO:0016021 9.92 SLC12A3 SCN4A RYR1 KCNJ2 KCNJ18 KCNE3
2 plasma membrane GO:0005886 9.61 TBC1D24 SLC12A3 SCN4A RYR1 KCNJ2 KCNJ18
3 intercalated disc GO:0014704 9.4 KCNJ2 ATP1A2
4 smooth endoplasmic reticulum GO:0005790 9.37 RYR1 KCNJ2
5 I band GO:0031674 9.26 RYR1 CACNA1S
6 sarcolemma GO:0042383 9.16 RYR1 ATP1A2
7 T-tubule GO:0030315 8.92 RYR1 KCNJ2 CACNA1S ATP1A2

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

(show all 18)
# Name GO ID Score Top Affiliating Genes
1 transmembrane transport GO:0055085 9.84 SLC12A3 SCN4A RYR1 CACNA1S
2 sodium ion transport GO:0006814 9.7 SLC12A3 SCN4A ATP1A2
3 cellular response to mechanical stimulus GO:0071260 9.58 KCNJ2 ATP1A2
4 muscle contraction GO:0006936 9.58 SCN4A RYR1 CACNA1S
5 protein homotetramerization GO:0051289 9.57 RYR1 KCNJ2
6 sodium ion transmembrane transport GO:0035725 9.56 SLC12A3 SCN4A
7 potassium ion transport GO:0006813 9.56 KCNJ2 KCNJ18 KCNE3 ATP1A2
8 regulation of heart rate by cardiac conduction GO:0086091 9.55 KCNJ2 KCNE3
9 regulation of ion transmembrane transport GO:0034765 9.55 SCN4A KCNJ2 KCNJ18 KCNE3 CACNA1S
10 regulation of cardiac muscle cell contraction GO:0086004 9.51 KCNJ2 ATP1A2
11 cellular potassium ion homeostasis GO:0030007 9.49 KCNJ2 ATP1A2
12 relaxation of cardiac muscle GO:0055119 9.48 KCNJ2 ATP1A2
13 membrane depolarization during cardiac muscle cell action potential GO:0086012 9.43 KCNJ2 ATP1A2
14 membrane repolarization during action potential GO:0086011 9.37 KCNJ2 KCNE3
15 cellular response to caffeine GO:0071313 9.32 RYR1 CACNA1S
16 potassium ion import across plasma membrane GO:1990573 9.26 SLC12A3 KCNJ2 KCNJ18 ATP1A2
17 ion transport GO:0006811 9.23 SLC12A3 SCN4A RYR1 KCNJ2 KCNJ18 KCNE3
18 regulation of membrane repolarization GO:0060306 9.16 KCNJ2

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

# Name GO ID Score Top Affiliating Genes
1 voltage-gated calcium channel activity GO:0005245 9.16 RYR1 CACNA1S
2 inward rectifier potassium channel activity GO:0005242 8.96 KCNJ2 KCNJ18
3 voltage-gated ion channel activity GO:0005244 8.92 SCN4A KCNJ2 KCNJ18 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 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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