Hypokalemic Periodic Paralysis malady

Genetics Home Reference: Hypokalemic periodic paralysis is a condition that causes episodes of extreme muscle weakness typically beginning in childhood or adolescence. Most often, these episodes involve a temporary inability to move muscles in the arms and legs. Attacks cause severe weakness or paralysis that usually lasts from hours to days. Some people may have episodes almost every day, while others experience them weekly, monthly, or only rarely. Attacks can occur without warning or can be triggered by factors such as rest after exercise, a viral illness, or certain medications. Often, a large, carbohydrate-rich meal or vigorous exercise in the evening can trigger an attack upon waking the following morning. Although affected individuals usually regain their muscle strength between attacks, repeated episodes can lead to persistent muscle weakness later in life.¹⁷

MalaCards: Hypokalemic Periodic Paralysis, also known as hypopp, is related to hypokalemic periodic paralysis type 2 and paralysis. An important gene associated with Hypokalemic Periodic Paralysis is CACNA1S (calcium channel, voltage-dependent, L type, alpha 1S subunit), and among its related pathways are nNOS Signaling in Skeletal Muscle and Netrin Signaling. The compounds (s)-(-)-bay k 8644 and (+-)-bay k 8644 have been mentioned in the context of this disorder. Affiliated tissues include skeletal muscle and thyroid, and related mouse phenotypes are muscle and behavior/neurological.

NIH Rare Diseases: Hypokalemic periodic paralysis is a condition that causes episodes of extreme muscle weakness typically beginning in childhood or adolescence. Most often, these episodes involve a temporary inability to move muscles in the arms and legs. The duration and frequency of the episodes may vary. Hypokalemic periodic paralysis is caused by mutations in the CACNA1S and SCN4A genes which are inherited in an autosomal dominant fashion. A small percentage of people with the characteristic features of hypokalemic periodic paralysis do not have identified mutations in these genes. In these cases, the cause of the condition is unknown. Paralytic crises can be treated with oral or IV potassium. Other management includes prevention of crises and support of specific symptoms.³⁰

Wikipedia: Hypokalemic periodic paralysis is a rare channelopathy characterized by muscle weakness or paralysis...⁴⁴ more...

GeneReviews summary for hpp

Aliases & Descriptions:

hypokalemic periodic paralysis 6 7 15 30 17 8 32 43 hypopp 15 30 16 17 hokpp 15 30 16 17 periodic hypokalemic paralysis 6 16 familial hypokalemic periodic paralysis (disorder) 6 hypokalemic periodic paralysis (disorder) 6 hypokalemic familial periodic paralysis 6

familial hypokalemic periodic paralysis 17 primary hypokalemic periodic paralysis 17 familial periodic paralysis (& ) 6 periodic paralysis i 6 westphall disease 17 hypokpp 17

Disease types for hypokalemic periodic paralysis family:

hypokalemic periodic paralysis type 1	hypokalemic periodic paralysis type 2

Diseases related to hypokalemic periodic paralysis by text searches and GeneDecks gene sharing:

(show top 50)    (show all 60)

id	Related Disease	Score	Top Affiliating Genes
1	hypokalemic periodic paralysis type 2	33.2	QDPR, SCN4A, SCN7A
2	paralysis	32.1	KCNE3, KCNJ18, SCN7A, SCN4A, CHKB, QDPR
3	myopathy	28.0	CACNA1S, RYR1, INS, QDPR, CHKB, SCN4A
4	malignant hyperthermia	27.5	CACNA1S, SCN7A, SCN4A, CHKB, QDPR, INS
5	paramyotonia congenita	13.2	SCN4A, SCN7A
6	normokalemic periodic paralysis	13.2	SCN4A, SCN7A
7	familial periodic paralysis	13.2	SCN4A, SCN7A
8	central core myopathy	13.1	CACNA1S, RYR1
9	right bundle branch block	13.0	KCNE3, CACNA1C
10	periodic paralyses	13.0	KCNE3, SCN4A, CACNA1S
11	hyperkalemic periodic paralysis	13.0	KCNE3, SCN4A, CACNA1S
12	hyperphenylalaninemia	12.9	CACNA1C, QDPR
13	malignant hyperthermia susceptibility	12.9	SCN4A, RYR1, CACNA1S
14	thyrotoxic periodic paralysis	12.8	CACNA1S, SCN4A, KCNJ18
15	brugada syndrome	12.6	CACNA1C, KCNE3
16	mayer-rokitansky-kuster-hauser syndrome	12.6	INS, RYR1, CACNA1S
17	hypomagnesemia	12.6	SLC12A3, INS
18	neuroleptic malignant syndrome	12.6	RYR1, CHKB
19	muscle disorders	12.5	RYR1, CHKB
20	adult dermatomyositis	12.5	INS, CHKB
21	rhabdomyolysis, cerivastatin-induced	12.5	CHKB, RYR1
22	hyperaldosteronism	12.5	SLC12A3, INS
23	hypersomnia	12.5	CHKB, INS
24	gas gangrene	12.5	INS, CHKB
25	myopathy congenital	12.4	RYR1, CHKB
26	myotonia	12.4	SCN7A, SCN4A, CHKB
27	neuromuscular disease	12.3	SCN4A, CHKB, RYR1
28	ventricular fibrillation	12.3	KCNE3, CHKB, CACNA1C
29	fainting	12.3	KCNE3, CHKB, CACNA1C
30	catecholaminergic polymorphic ventricular tachycardia	12.2	CHKB, RYR1
31	diabetic ketoacidosis	12.2	INS, CHKB
32	secondary hyperparathyroidism of renal origin	12.2	INS, RYR1, CACNA1C, CACNA1S
33	myostatin-related muscle hypertrophy	12.2	INS, CHKB, SCN4A
34	hyperparathyroidism	12.2	CACNA1S, CACNA1C, RYR1, INS
35	hypocalcemia	12.1	SLC12A3, CHKB
36	myositis	12.0	CHKB, INS, RYR1
37	centronuclear myopathy	11.9	RYR1, CHKB
38	acute pancreatitis	11.9	CHKB, INS, RYR1
39	hypoglycemia	11.9	CHKB, INS, CACNA1C
40	myotonic dystrophy	11.8	RYR1, INS, CHKB, SCN4A
41	hypertrophic cardiomyopathy	11.8	CACNA1S, CACNA1C, INS, CHKB
42	atrial fibrillation	11.8	CACNA1C, INS, CHKB, KCNE3
43	hyperthyroidism	11.7	KCNJ18, CHKB, INS, CACNA1S
44	graves' disease	11.7	KCNJ18, CHKB, INS, CACNA1S
45	myasthenia gravis	11.5	CACNA1S, RYR1, INS, QDPR, CHKB
46	congenital myasthenic syndrome	11.5	CACNA1S, RYR1, INS, QDPR, CHKB
47	neuropathy	11.4	SCN4A, CHKB, INS, RYR1
48	hypokalemia	11.4	CACNA1S, SLC12A3, INS, SCN4A, KCNJ18, KCNE3
49	arrhythmogenic right ventricular dysplasia/cardiomyopathy multi-gene panels	11.1	CACNA1C, RYR1, INS, CHKB, SCN4A, KCNE3
50	dmd-associated dilated cardiomyopathy	11.1	CACNA1S, CACNA1C, RYR1, INS, QDPR, CHKB

Approved drugs:

Drug clinical trials:

Genetic tests related to hypokalemic periodic paralysis:

id	Genetic test	Affiliating Genes
1	Hypokalemic Periodic Paralysis clinical/research	SCN4A, CACNA1S

MalaCards organs/tissues related to hypokalemic periodic paralysis:

²²

MGI Mouse Phenotypes related to hypokalemic periodic paralysis:

²⁵

id	Description	MGI Source Accession	Score	Top Affiliating Genes
1	muscle phenotype	MP:0005369	7.9	CACNA1S, CACNA1C, RYR1, CHKB, SCN4A
2	behavior/neurological phenotype	MP:0005386	7.2	SCN7A, SCN4A, CHKB, INS, RYR1, CACNA1C
3	homeostasis/metabolism phenotype	MP:0005376	7.1	KCNE3, CHKB, INS, SLC12A3, RYR1, CACNA1C

Articles related to hypokalemic periodic paralysis:

(show all 45)

id	Title	Authors	Year	Affiliating Genes
1	Identification and functional characterization of Kir 2.6 mutations associated with non-familial hypokalemic periodic paralysis. (21665951)	Cheng C.J.... Huang C.L.	2011	KCNJ18
2	Mutations in potassium channel Kir2.6 cause susceptib ility to thyrotoxic hypokalemic periodic paralysis. (20074522)	Ryan D.P.... PtA!cek L.J.	2010	KCNJ18
3	Hypokalemic periodic paralysis due to the SCN4A R672H mutation in a Turkish family. (21043388)	Incecik F.... Lehman-Horn F.	2010	SCN4A
4	Voltage sensor charge loss accounts for most cases of hypokalemic periodic paralysis. (19118277)	Matthews E.... Hanna M.G.	2009	CACNA1S
5	Progressive muscle atrophy with hypokalemic periodic paralysis and calcium channel mutation. (17587224)	Meyer T.... Spuler S.	2008	CACNA1S
6	Myopathy as the first symptom of hypokalemic periodic paralysis--case report of a girl from a Polish family with CACNA1S (R1239G) mutation. (18229654)	Winczewska-Wiktor A.... Jurkat-Rott K.	2007	CACNA1S
7	Hypokalemic periodic paralysis in a patient with acqu ired growth hormone deficiency. (17556873)	Lanzi R.... Losa M.	2007	INS
8	Toxic thyroid adenoma presenting as hypokalemic periodic paralysis. (17917308)	Tagami T.... Naruse M.	2007	SCN4A
9	The genotype and clinical phenotype of Korean patients with familial hypokalemic periodic paralysis. (18162704)	Kim J.-B.... Lee B.C.	2007	CACNA1S
10	A Na+ channel mutation linked to hypokalemic periodic paralysis exposes a proton-selective gating pore. (17591984)	Struyk A.F.... Cannon S.C.	2007	SCN4A
11	Gating defects of a novel Na+ channel mutant causing hypokalemic periodic paralysis. (16890191)	Carle T.... Tabti N.	2006	SCN4A
12	Mutation screening in Chinese hypokalemic periodic paralysis patients. (16386935)	Wang W.... Ning G.	2006	SCN4A
13	Gene analysis of the calcium channel 1 subunit and clinical studies for two patients with hypokalemic periodic paralysis. (17185904)	Kageyama K.... Suda T.	2006	CACNA1S
14	Novel CACNA1S mutation causes autosomal dominant hypokalemic periodic paralysis in a Chinese family. (15726306)	Wang Q.... Yang J.	2005	CACNA1S
15	Skeletal muscle dihydropyridine-sensitive calcium channel (CACNA1S) gene mutations in chinese patients with hypokalemic periodic paralysis. (15711422)	Lin S.H.... Kao M.C.	2005	CACNA1S
16	A Korean family of hypokalemic periodic paralysis with mutation in a voltage-gated calcium channel (R1239G). (15716625)	Kim J.B.... Hur J.K.	2005	CACNA1S
17	Manifestation, management and molecular analysis of candidate genes in two rare cases of thyrotoxic hypokalemic periodic paralysis. (15795511)	Schalin-Jantti C.... Valimaki M.J.	2005	CACNA1S
18	Thyrotoxic hypokalemic periodic paralysis, an endocrine emergency: clinical and genetic features in 25 patients (15611833)	Silva M.R.... Maciel R.M.	2004	CACNA1S
19	A family of hypokalemic periodic paralysis with CACNA1S gene mutation showing incomplete penetrance in women. (15098604)	Kawamura S.... Seki K.	2004	CACNA1S
20	Absence of ion channels CACN1AS and SCN4A mutations in thyrotoxic hypokalemic periodic paralysis. (15072700)	Ng W.Y.... Cheah J.S.	2004	CACNA1S
21	Mutation analysis of two patients with hypokalemic periodic paralysis and suspected malignant hyperthermia. (15221887)	Marchant C.L.... Robinson R.L.	2004	RYR1
22	From gene to diseases; hypokalemic periodic paralysis (15185439)	Links T.P.... van der Hoeven J.H.	2004	CACNA1S
23	Mutation screening in Korean hypokalemic periodic paralysis patients: a novel SCN4A Arg672Cys mutation. (15482957)	Kim M.K.... Kim S.M.	2004	SCN4A
24	Cold induces shifts of voltage dependence in mutant SCN4A, causing hypokalemic periodic paralysis. (14557559)	Sugiura Y.... Yamamoto T.	2003	SCN4A
25	A case of Gitelman's syndrome presenting with the hypokalemic periodic paralysis (12561088)	Saiki S.... Hirose G.	2002	SLC12A3
26	A mutation in the KCNE3 potassium channel gene is associated with susceptibility to thyrotoxic hypokalemic periodic paralysis. (12414843)	Dias da Silva M.R.... Maciel R.M.B.	2002	SCN4A, KCNE3
27	A case of familial hypokalemic periodic paralysis with hyperuricemia during paralytic attack and genetic analysis of the pedigree (11808349)	Katsuno M.... Sobue G.	2001	CACNA1S
28	Familial hypokalemic periodic paralysis (15775665)	Ikeda Y.... Okamoto K.	2001	CACNA1S
29	Sodium channel gene mutations in hypokalemic periodic paralysis: an uncommon cause in the UK. (11591859)	Davies N.P.... Hanna M.G.	2001	CACNA1S
30	Sodium channel inactivation defects are associated with acetazolamide-exacerbated hypokalemic periodic paralysis. (11558801)	Bendahhou S.... Ptacek L.J.	2001	SCN4A
31	Muscle weakness in a Japanese family of Arg1239His mutation hypokalemic periodic paralysis. (11555352)	Kusumi M.... Nakashima K.	2001	CACNA1C
32	Hypokalemic periodic paralysis and mutations in the CACNL1A3 gene: case study in a Japanese family. (10881598)	Wada T.... Koizumi S.	2000	CACNA1S
33	Voltage-sensor sodium channel mutations cause hypokalemic periodic paralysis type 2 by enhanced inactivation and reduced current. (10944223)	Jurkat-Rott K.... Lehmann-Horn F.	2000	SCN4A, QDPR, SCN7A
34	A novel sodium channel mutation in a family with hypokalemic periodic paralysis. (10599760)	Bulman D.E.... Ebers G.C.	1999	CACNA1S
35	Gating of the L-type Ca channel in human skeletal myotubes: an activation defect caused by the hypokalemic periodic paralysis mutation R528H. (9852570)	Morrill J.A.... Cannon S.C.	1998	CACNA1S
36	Identification of mutations in the CACNL1A3 gene in 13 families of Scandinavian origin having hypokalemic periodic paralysis and evidence of a founder effect in Danish families. (9066893)	Sillen A.... Wadelius C.	1997	CACNA1S
37	Mutation analysis of the CACNL1A3 gene in Japanese hypokalemic periodic paralysis families (9436445)	Ikeda Y.... Shoji M.	1997	CACNA1C
38	Genotype-phenotype correlations of DHP receptor alpha 1-subunit gene mutations causing hypokalemic periodic paralysis. (9132138)	Fouad G.... Ptacek L.J.	1997	CACNA1S
39	Hypokalemic periodic paralysis mutations: confirmation of mutation and analysis of founder effect. (8845715)	Grosson C.L.... Brown R.H.	1996	CACNA1S
40	Hypokalemic periodic paralysis and the dihydropyridine receptor (CACNL1A3): genotype/phenotype correlations for two predominant mutations and evidence for the absence of a founder effect in 16 caucasian families. (7847370)	Elbaz A.... Monnier N.	1995	CACNA1S
41	A calcium channel mutation causing hypokalemic periodic paralysis. (7987325)	Jurkatt-Rott K.... Fontaine B.	1994	CACNA1S
42	Dihydropyridine receptor mutations cause hypokalemic periodic paralysis. (8004673)	Ptacek L.J.... Leppert M.F.	1994	CACNA1S
43	Hypokalemic Periodic Paralysis (20301512)	Sternberg D.... Fontaine B.	1993	CACNA1S
44	Exclusion of linkage between hypokalemic periodic paralysis (HOKPP) and three candidate loci. (1330884)	Casley W.L.... Ebers G.C.	1992	SCN4A
45	Increase in serum myoglobin, creatine kinase, and free fatty acids, during recovery from a paralytic attack in hypokalemic periodic paralysis. (1660381)	De Keyser J.... Ebinger G.	1991	CHKB

Genes related to hypokalemic periodic paralysis according to GeneCards:

(show all 11)

id	Symbol	Description	Score	GeneCards Section Context
1	CACNA1S	calcium channel, voltage-dependent, L type, alpha 1S subunit	11.1	Publications, Aliases & Descriptions, Summaries
2	KCNE3	potassium voltage-gated channel, Isk-related family, member 3	11.1	Summaries, Publications
3	SCN4A	sodium channel, voltage-gated, type IV, alpha subunit	11.1	Publications
4	SCN7A	sodium channel, voltage-gated, type VII, alpha subunit	11.1	Publications
5	QDPR	quinoid dihydropteridine reductase	11.1	Publications
6	RYR1	ryanodine receptor 1 (skeletal)	11.1	Publications
7	CACNA1C	calcium channel, voltage-dependent, L type, alpha 1C subunit	11.1	Publications
8	KCNJ18	potassium inwardly-rectifying channel, subfamily J, member 18	11.0	Publications
9	SLC12A3	solute carrier family 12 (sodium/chloride transporters), member 3	11.0	Publications
10	CHKB	choline kinase beta	11.0	Publications
11	INS	insulin	11.0	Publications

Pathways related to hypokalemic periodic paralysis according to GeneDecks:

(show all 14)

id	Pathway	Score	Top Affiliating Genes
1	nNOS Signaling in Skeletal Muscle36	9.6	RYR1, CACNA1C, CACNA1S
2	Netrin Signaling36	9.5	RYR1, CACNA1C, CACNA1S
3	Beta-Adrenergic Signaling36	9.5	RYR1, CACNA1C, CACNA1S
4	Dopamine-DARPP32 Feedback onto cAMP Pathway36	9.4	KCNE3, CACNA1C, CACNA1S
5	MODY (Maturity-Onset Diabetes of Young)36	9.4	CACNA1S, CACNA1C, INS
6	GHRH Signaling36	9.4	SCN7A, SCN4A, CACNA1C, CACNA1S
7	Presenilin-Mediated Signaling36	9.3	RYR1, CACNA1C, CACNA1S
8	Aldosterone Signaling in Epithelial Cells36	9.3	SLC12A3, SCN4A, SCN7A
9	Calcium signaling pathway20	9.2	CACNA1S, CACNA1C, RYR1
10	Anti-diabetic Drug Potassium Channel Inhibitors Pathway, Pharmacodynamics34	9.2	INS, CACNA1C
11	Intracellular Calcium Signaling36	9.1	CACNA1S, CACNA1C, RYR1, QDPR
12	PKA Signaling36	8.9	CACNA1S, CACNA1C, RYR1, SCN4A, SCN7A
13	Activation of cAMP-Dependent PKA36	8.9	CACNA1S, CACNA1C, RYR1, SCN4A, SCN7A
14	cAMP Pathway36	8.8	CACNA1S, CACNA1C, RYR1, SCN4A, SCN7A

Compounds related to hypokalemic periodic paralysis according to GeneDecks:

(show all 33)

id	Compound	Score	Top Affiliating Genes
1	(s)-(-)-bay k 864442	10.1	CACNA1S, CACNA1C
2	(+-)-bay k 864442	10.1	CACNA1S, CACNA1C
3	fpl 6417642	10.1	CACNA1C, CACNA1S
4	Magnesium Sulfate9 9	11.1	CACNA1S, CACNA1C
5	nisoldipine32 9 9	12.1	CACNA1C, CACNA1S
6	isradipine32 9 42 9	13.0	CACNA1C, CACNA1S
7	Cinnarizine9 9	11.0	CACNA1S, CACNA1C
8	nilvadipine32 9 9	12.0	CACNA1S, CACNA1C
9	nimodipine32 9 42 9	13.0	CACNA1C, CACNA1S
10	nitrendipine32 9 9	12.0	CACNA1C, CACNA1S
11	mibefradil32 9 9	11.9	CACNA1S, CACNA1C
12	felodipine32 9 9	11.9	CACNA1S, CACNA1C
13	ryanodine32	9.8	QDPR, RYR1, CACNA1S
14	amlodipine32 9 18 9	12.6	CACNA1S, CACNA1C
15	dantrolene32 9 9	11.6	RYR1, CHKB
16	thiazide32	9.5	SLC12A3, INS
17	diazoxide32 42 9 9	12.5	INS, SLC12A3
18	beta-hydroxybutyrate32	9.4	INS, CHKB
19	nifedipine32 9 9	11.3	QDPR, RYR1, CACNA1C, CACNA1S
20	succinylcholine32 9 9	11.3	RYR1, CHKB, SCN4A
21	rosuvastatin32 34 9 9	12.2	CHKB, INS
22	lead32	9.2	RYR1, QDPR, CHKB
23	sodium32 18	10.1	CACNA1S, SLC12A3, SCN4A, SCN7A
24	gemfibrozil32 9 9	11.1	CHKB, INS
25	chloride32	9.1	SCN4A, SLC12A3, RYR1
26	dihydropyridine32	9.0	SCN4A, QDPR, RYR1, CACNA1C, CACNA1S
27	mgatp32	8.9	CHKB, RYR1
28	tacrolimus32 34 9 9	11.7	RYR1, INS, QDPR, CHKB
29	norepinephrine32 9 18 9	11.7	RYR1, INS, QDPR, CHKB
30	arginine32	8.5	CACNA1S, RYR1, INS, CHKB, SCN4A
31	potassium32 9 18 9	11.4	RYR1, SLC12A3, CHKB, SCN4A, KCNE3
32	alanine32	8.0	RYR1, SLC12A3, INS, QDPR, CHKB
33	calcium32 9 18 9	10.2	CACNA1S, CACNA1C, RYR1, SLC12A3, QDPR, CHKB

Cellular components related to hypokalemic periodic paralysis according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	voltage-gated sodium channel complex	GO:001518	9.8	SCN7A, SCN4A
2	sarcoplasmic reticulum	GO:016529	9.8	RYR1, CACNA1S
3	I band	GO:031674	9.7	CACNA1S, RYR1
4	voltage-gated calcium channel complex	GO:005891	9.4	CACNA1C, CACNA1S
5	T-tubule	GO:030315	9.4	RYR1, CACNA1C, CACNA1S

Biological processes related to hypokalemic periodic paralysis according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	sodium ion transport	GO:006814	9.2	SCN7A, SCN4A, SLC12A3
2	muscle contraction	GO:006936	8.8	SCN7A, SCN4A, RYR1, CACNA1S

Molecular functions related to hypokalemic periodic paralysis according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	voltage-gated sodium channel activity	GO:005248	9.8	SCN7A, SCN4A
2	voltage-gated calcium channel activity	GO:005245	9.0	RYR1, CACNA1C, CACNA1S