MCID: PRM028
MIFTS: 49

Paramyotonia Congenita

Categories: Genetic diseases, Rare diseases, Neuronal diseases

Aliases & Classifications for Paramyotonia Congenita

MalaCards integrated aliases for Paramyotonia Congenita:

Name: Paramyotonia Congenita 54 50 25 56 13 52 69
Paramyotonia Congenita of Von Eulenburg 50 24 25 56 71 29
Pmc 50 25 71
Paralysis Periodica Paramyotonica 50 71
Paralysis Periodica Paramyotonia 25 71
Eulenburg Disease 50 25
Paramyotonia Congenita Without Cold Paralysis 71
Von Eulenburg Paramyotonia Congenita 50
Myotonia Congenita Intermittens 50
Von Eulenberg's Disease 25
Pc 24

Characteristics:

Orphanet epidemiological data:

56
paramyotonia congenita of von eulenburg
Inheritance: Autosomal dominant; Age of onset: Adolescent,Adult,Childhood;

OMIM:

54
Inheritance:
autosomal dominant

Miscellaneous:
onset in infancy or early childhood
highly variable phenotype
allelic disorder to hyperkalemic periodic paralysis (hypp, )
affected females report aggravation of symptoms during menstrual periods and pregnancy, with alleviation after menopause
allelic disorder to potassium-aggravated myotonia
allelic disorder to hypokalemic periodic paralysis (hokpp, )
some patients may present with transient neonatal hypotonia, and then later develop classic pmc in childhood
alcohol may alleviate symptoms
patients may have a combination phenotype of pmc and hypp (see )


HPO:

32
paramyotonia congenita:
Onset and clinical course phenotypic variability infantile onset
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 56  
Rare neurological diseases


External Ids:

OMIM 54 168300
Orphanet 56 ORPHA684
MESH via Orphanet 43 C538616
UMLS via Orphanet 70 C1868617 C0221055
ICD10 via Orphanet 34 G71.1
MeSH 42 D020967

Summaries for Paramyotonia Congenita

Genetics Home Reference : 25 Paramyotonia congenita is a disorder that affects muscles used for movement (skeletal muscles). Beginning in infancy or early childhood, people with this condition experience bouts of sustained muscle tensing (myotonia) that prevent muscles from relaxing normally. Myotonia causes muscle stiffness that typically appears after exercise and can be induced by muscle cooling. This stiffness chiefly affects muscles in the face, neck, arms, and hands, although it can also affect muscles used for breathing and muscles in the lower body. Unlike many other forms of myotonia, the muscle stiffness associated with paramyotonia congenita tends to worsen with repeated movements.

MalaCards based summary : Paramyotonia Congenita, also known as paramyotonia congenita of von eulenburg, is related to myotonia congenita, dominant and myotonia, and has symptoms including muscle weakness, muscle stiffness and neonatal hypotonia. An important gene associated with Paramyotonia Congenita is SCN4A (Sodium Voltage-Gated Channel Alpha Subunit 4), and among its related pathways/superpathways are Neuropathic Pain-Signaling in Dorsal Horn Neurons and Neuroscience. The drugs Dichlorphenamide and Mexiletine have been mentioned in the context of this disorder. Affiliated tissues include skeletal muscle, tongue and testes.

NIH Rare Diseases : 50 paramyotonia congenita is an inherited condition that affects muscles used for movement (skeletal muscles), mainly in the face, neck, arms, and hands. symptoms begin in infancy or early childhood and include episodes of sustained muscle tensing (myotonia) that prevent muscles from relaxing normally and lead to muscle weakness.  symptoms in paramyotonia congenita worsen during exposure to cold temperatures, and unlike many other forms of myotonia, worsen with exercise and repeated movements. this condition is caused by mutations in the scn4a gene and is inherited in an autosomal dominant pattern. last updated: 5/18/2012

UniProtKB/Swiss-Prot : 71 Paramyotonia congenita of von Eulenburg: An autosomal dominant channelopathy characterized by myotonia, increased by exposure to cold, intermittent flaccid paresis, not necessarily dependent on cold or myotonia, lability of serum potassium, non-progressive nature and lack of atrophy or hypertrophy of muscles. In some patients, myotonia is not increased by cold exposure (paramyotonia without cold paralysis). Patients may have a combination phenotype of PMC and HYPP.

Wikipedia : 72 Paramyotonia congenita (PC), also known as paramyotonia congenita of von Eulenburg or Eulenburg disease,... more...

Description from OMIM: 168300

Related Diseases for Paramyotonia Congenita

Diseases related to Paramyotonia Congenita via text searches within MalaCards or GeneCards Suite gene sharing:

id Related Disease Score Top Affiliating Genes
1 myotonia congenita, dominant 11.0
2 myotonia 10.4
3 myotonia congenita 10.3
4 episodic ataxia 9.9
5 myotonic dystrophy 9.9
6 ataxia 9.9
7 nevus cavernosus 9.7 SCN4A SCN7A
8 nova syndrome 9.6 SCN4A SCN7A
9 sessile serrated polyposis cancer syndrome 9.4 SCN4A SCN7A
10 myotonia congenita, atypical, acetazolamide-responsive 8.9 KCNA1 SCN4A SCN7A

Graphical network of the top 20 diseases related to Paramyotonia Congenita:



Diseases related to Paramyotonia Congenita

Symptoms & Phenotypes for Paramyotonia Congenita

Symptoms via clinical synopsis from OMIM:

54

Muscle Soft Tissue:
muscle hypertrophy
muscle stiffness
muscle pain
percussion myotonia
myotonia, cold-sensitive, predominantly of face, tongue, forearm, and hand precipitated by muscle cooling or cold exposure or rest after exercise
more
Abdomen- Gastroin testinal:
poor feeding in early life

Respiratory:
inspiratory stridor in early life


Clinical features from OMIM:

168300

Human phenotypes related to Paramyotonia Congenita:

32 (show all 10)
id Description HPO Frequency HPO Source Accession
1 muscle weakness 32 HP:0001324
2 muscle stiffness 32 HP:0003552
3 neonatal hypotonia 32 occasional (7.5%) HP:0001319
4 myalgia 32 HP:0003326
5 feeding difficulties 32 HP:0011968
6 percussion myotonia 32 HP:0010548
7 handgrip myotonia 32 HP:0012899
8 inspiratory stridor 32 HP:0005348
9 skeletal muscle hypertrophy 32 HP:0003712
10 paradoxical myotonia 32 HP:0011809

UMLS symptoms related to Paramyotonia Congenita:


muscular stiffness, myalgia

Drugs & Therapeutics for Paramyotonia Congenita

Drugs for Paramyotonia Congenita (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 15)
id Name Status Phase Clinical Trials Cas Number PubChem Id
1
Dichlorphenamide Approved Phase 3 120-97-8 3038
2
Mexiletine Approved Phase 3,Phase 2 31828-71-4 4178
3
Lamotrigine Approved, Investigational Phase 3 84057-84-1 3878
4 Carbonic Anhydrase Inhibitors Phase 3
5 Anti-Arrhythmia Agents Phase 3,Phase 2
6 Diuretics, Potassium Sparing Phase 3,Phase 2
7 Sodium Channel Blockers Phase 3,Phase 2
8 Anticonvulsants Phase 3
9 calcium channel blockers Phase 3
10 Calcium, Dietary Phase 3
11 Excitatory Amino Acid Antagonists Phase 3
12 Excitatory Amino Acids Phase 3
13 Neurotransmitter Agents Phase 3
14
Lidocaine Approved, Vet_approved Phase 2 137-58-6 3676
15
Ranolazine Approved, Investigational Phase 2 142387-99-3, 95635-55-5 56959

Interventional clinical trials:


id 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 Mexiletine and Non Dystrophic Myotonias Completed NCT02336477 Phase 3 Mexiletine;placebo
3 Lamotrigine as Treatment of Myotonia Completed NCT01939561 Phase 3 Lamotrigine;Placebo
4 Combined N-of-1 Trials Mexiletine vs Placebo in Patients With Non-Dystrophic Myotonia (NDM) Completed NCT02045667 Phase 2 Mexiletine;Placebo
5 Study of Ranolazine in Myotonia Congenita, Paramyotonia Congenita and Myotonic Dystrophy Type 1 Recruiting NCT02251457 Phase 2 Ranolazine
6 Characteristics of Nondystrophic Myotonias Completed NCT00244413

Search NIH Clinical Center for Paramyotonia Congenita

Genetic Tests for Paramyotonia Congenita

Genetic tests related to Paramyotonia Congenita:

id Genetic test Affiliating Genes
1 Paramyotonia Congenita of Von Eulenburg 29 24 SCN4A

Anatomical Context for Paramyotonia Congenita

MalaCards organs/tissues related to Paramyotonia Congenita:

39
Skeletal Muscle, Tongue, Testes

Publications for Paramyotonia Congenita

Articles related to Paramyotonia Congenita:

(show top 50) (show all 119)
id Title Authors Year
1
N1366S mutation of human skeletal muscle sodium channel causes paramyotonia congenita. ( 28940424 )
2017
2
Propofol Reduces Succinylcholine-induced Muscle Rigidity in a Patient with Paramyotonia Congenita. ( 28298805 )
2017
3
[Paramyotonia congenita caused by a novel mutation of SCN4A gene in a Chinese family]. ( 27060299 )
2016
4
Identification of genetic variations of a Chinese family with paramyotonia congenita via whole exome sequencing. ( 26484179 )
2015
5
Teaching video neuroimages: lid lag sign and diplopia in paramyotonia congenita. ( 25074897 )
2014
6
Paramyotonia congenita: from clinical diagnosis to in silico protein modeling analysis. ( 22507243 )
2012
7
Ranolazine block of human Na v 1.4 sodium channels and paramyotonia congenita mutants. ( 21317558 )
2011
8
A case of paramyotonia congenita without periodic paralysis: electrophysiological and molecular genetic studies. ( 20445432 )
2010
9
Paramyotonia congenita in 22 members of an Arab (Omani) kindred. ( 19168830 )
2010
10
Relief from episodic weakness with pyridostigmine in paramyotonia congenita: a family study. ( 19768756 )
2010
11
A patient with episodic ataxia and paramyotonia congenita due to mutations in KCNA1 and SCN4A. ( 19770477 )
2009
12
Clinical, electrophysiological and genetic features of a large Australian family with paramyotonia congenita. ( 19296818 )
2009
13
Reduced muscle-fiber conduction but normal slowing after cold exposure in paramyotonia congenita. ( 17823953 )
2008
14
Differential effects of paramyotonia congenita mutations F1473S and F1705I on sodium channel gating. ( 18690054 )
2008
15
[Eulenburg's paramyotonia congenita]. ( 18033047 )
2007
16
Efficacy of propafenone in paramyotonia congenita. ( 17389319 )
2007
17
Anesthetic management for subtotal gastrectomy in a patient with paramyotonia congenita. ( 18008119 )
2007
18
A1152D mutation of the Na+ channel causes paramyotonia congenita and emphasizes the role of DIII/S4-S5 linker in fast inactivation. ( 15790667 )
2005
19
Disabling foot cramping in a runner secondary to paramyotonia congenita: a case report. ( 15319111 )
2004
20
Temperature-sensitive defects in paramyotonia congenita mutants R1448C and T1313M. ( 15318338 )
2004
21
Functional characterization and cold sensitivity of T1313A, a new mutation of the skeletal muscle sodium channel causing paramyotonia congenita in humans. ( 14617673 )
2004
22
Pyloromyotomy in a patient with paramyotonia congenita. ( 14693588 )
2004
23
Paramyotonia congenita and skeletal sodium channelopathy. ( 14518660 )
2003
24
Thr1313Met mutation in skeletal muscle sodium channels in a Japanese family with paramyotonia congenita. ( 14518676 )
2003
25
Mechanisms of cold sensitivity of paramyotonia congenita mutation R1448H and overlap syndrome mutation M1360V. ( 12562902 )
2003
26
Severe infantile hyperkalaemic periodic paralysis and paramyotonia congenita: broadening the clinical spectrum associated with the T704M mutation in SCN4A. ( 12933953 )
2003
27
Paramyotonia congenita with an SCN4A mutation affecting cardiac repolarization. ( 12552059 )
2003
28
Paramyotonia congenita due to a de novo mutation: a case report. ( 12872329 )
2003
29
A Korean family with Arg1448Cys mutation of SCN4A channel causing paramyotonia congenita: electrophysiologic, histopathologic, and molecular genetic studies. ( 12483017 )
2002
30
The anesthetic propofol modulates gating in paramyotonia congenita mutant muscle sodium channels. ( 11360256 )
2001
31
Hyperkalemic periodic paralysis and paramyotonia congenita--a novel sodium channel mutation. ( 11757950 )
2001
32
Patch clamp studies of the thr1313met mutant sodium channel causing paramyotonia congenita. ( 11054753 )
2000
33
Clinical, electrophysiological, and molecular genetic studies in a new family with paramyotonia congenita. ( 10727489 )
2000
34
Different effects of mexiletine on two mutant sodium channels causing paramyotonia congenita and hyperkalemic periodic paralysis. ( 10677861 )
2000
35
Mutant channels contribute <50% to Na+ current in paramyotonia congenita muscle. ( 10356061 )
1999
36
Electro-oculographic findings in an unusual case of paramyotonia congenita. ( 10417805 )
1999
37
Lack of sodium channel mutation in an Italian family with paramyotonia congenita. ( 10534266 )
1999
38
A novel mutation in the gene for the adult skeletal muscle sodium channel alpha-subunit (SCN4A) that causes paramyotonia congenita of von Eulenburg. ( 10369308 )
1999
39
Caesarean section in a patient with paramyotonia congenita. ( 10520399 )
1999
40
Characterization of a new sodium channel mutation at arginine 1448 associated with moderate Paramyotonia congenita in humans. ( 10381583 )
1999
41
Effects of temperature and mexiletine on the F1473S Na+ channel mutation causing paramyotonia congenita. ( 9716710 )
1998
42
Functional expression of the Ile693Thr Na+ channel mutation associated with paramyotonia congenita in a human cell line. ( 9508833 )
1998
43
A defect in skeletal muscle sodium channel deactivation exacerbates hyperexcitability in human paramyotonia congenita. ( 9503326 )
1998
44
Fast- and slow-gating modes of the sodium channel are altered by a paramyotonia congenita-linked mutation. ( 10206477 )
1998
45
Paramyotonia congenita and hyperkalemic periodic paralysis associated with a Met 1592 Val substitution in the skeletal muscle sodium channel alpha subunit--a large kindred with a novel phenotype. ( 9131651 )
1997
46
Temperature-sensitive repetitive discharges in paramyotonia congenita. ( 9040658 )
1997
47
Human Na+ channel fast and slow inactivation in paramyotonia congenita mutants expressed in Xenopus laevis oocytes. ( 9130156 )
1997
48
C4342T-mutation in the SCN4A gene on chromosome 17q in a Swedish family with paramyotonia congenita (Eulenburg)--correlations with clinical, neurophysiological and muscle biopsy data. ( 9196904 )
1997
49
Two human paramyotonia congenita mutations have opposite effects on lidocaine block of Na+ channels expressed in a mammalian cell line. ( 8910215 )
1996
50
Paramyotonia congenita mutations reveal different roles for segments S3 and S4 of domain D4 in hSkM1 sodium channel gating. ( 8833340 )
1996

Variations for Paramyotonia Congenita

UniProtKB/Swiss-Prot genetic disease variations for Paramyotonia Congenita:

71 (show all 20)
id Symbol AA change Variation ID SNP ID
1 SCN4A p.Thr704Met VAR_001562 rs80338957
2 SCN4A p.Ser804Phe VAR_001563 rs121908546
3 SCN4A p.Ala1156Thr VAR_001565 rs80338958
4 SCN4A p.Val1293Ile VAR_001566 rs121908551
5 SCN4A p.Gly1306Ala VAR_001567 rs80338792
6 SCN4A p.Gly1306Glu VAR_001568 rs80338792
7 SCN4A p.Gly1306Val VAR_001569 rs80338792
8 SCN4A p.Thr1313Met VAR_001570 rs121908547
9 SCN4A p.Leu1433Arg VAR_001571 rs121908550
10 SCN4A p.Arg1448Cys VAR_001572 rs121908544
11 SCN4A p.Arg1448His VAR_001573 rs121908545
12 SCN4A p.Val1589Met VAR_001574 rs121908548
13 SCN4A p.Ala1152Asp VAR_022341
14 SCN4A p.Gly1456Glu VAR_037107 rs121908554
15 SCN4A p.Gln270Lys VAR_054936
16 SCN4A p.Leu1436Pro VAR_054947
17 SCN4A p.Arg1448Leu VAR_054948
18 SCN4A p.Phe1473Ser VAR_054949
19 SCN4A p.Phe1705Ile VAR_054952
20 SCN4A p.Ile693Thr VAR_065231 rs80338956

ClinVar genetic disease variations for Paramyotonia Congenita:

6 (show all 12)
id Gene Variation Type Significance SNP ID Assembly Location
1 SCN4A NM_000334.4(SCN4A): c.4342C> T (p.Arg1448Cys) single nucleotide variant Pathogenic rs121908544 GRCh37 Chromosome 17, 62019300: 62019300
2 SCN4A NM_000334.4(SCN4A): c.4343G> A (p.Arg1448His) single nucleotide variant Pathogenic rs121908545 GRCh37 Chromosome 17, 62019299: 62019299
3 SCN4A NM_000334.4(SCN4A): c.3917G> T (p.Gly1306Val) single nucleotide variant Pathogenic rs80338792 GRCh37 Chromosome 17, 62021206: 62021206
4 SCN4A NM_000334.4(SCN4A): c.3938C> T (p.Thr1313Met) single nucleotide variant Pathogenic rs121908547 GRCh37 Chromosome 17, 62021185: 62021185
5 SCN4A NM_000334.4(SCN4A): c.4765G> A (p.Val1589Met) single nucleotide variant Pathogenic rs121908548 GRCh37 Chromosome 17, 62018877: 62018877
6 SCN4A NM_000334.4(SCN4A): c.4298T> G (p.Leu1433Arg) single nucleotide variant Pathogenic rs121908550 GRCh37 Chromosome 17, 62019344: 62019344
7 SCN4A NM_000334.4(SCN4A): c.3917G> C (p.Gly1306Ala) single nucleotide variant Pathogenic rs80338792 GRCh37 Chromosome 17, 62021206: 62021206
8 SCN4A NM_000334.4(SCN4A): c.3877G> A (p.Val1293Ile) single nucleotide variant Pathogenic rs121908551 GRCh37 Chromosome 17, 62022068: 62022068
9 SCN4A NM_000334.4(SCN4A): c.4367G> A (p.Gly1456Glu) single nucleotide variant Pathogenic rs121908554 GRCh37 Chromosome 17, 62019275: 62019275
10 SCN4A NM_000334.4(SCN4A): c.4428G> A (p.Met1476Ile) single nucleotide variant Pathogenic rs121908559 GRCh37 Chromosome 17, 62019214: 62019214
11 SCN4A NM_000334.4(SCN4A): c.2078T> C (p.Ile693Thr) single nucleotide variant Pathogenic rs80338956 GRCh37 Chromosome 17, 62034820: 62034820
12 SCN4A NM_000334.4(SCN4A): c.421A> G (p.Ile141Val) single nucleotide variant Pathogenic rs121908561 GRCh37 Chromosome 17, 62049557: 62049557

Expression for Paramyotonia Congenita

Search GEO for disease gene expression data for Paramyotonia Congenita.

Pathways for Paramyotonia Congenita

Pathways related to Paramyotonia Congenita according to GeneCards Suite gene sharing:

id Super pathways Score Top Affiliating Genes
1
Show member pathways
11.91 SCN4A SCN7A
2 11.77 SCN4A SCN7A
3
Show member pathways
11.25 SCN4A SCN7A
4
Show member pathways
10.83 SCN4A SCN7A
5 10.1 SCN4A SCN7A

GO Terms for Paramyotonia Congenita

Cellular components related to Paramyotonia Congenita according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 voltage-gated sodium channel complex GO:0001518 8.62 SCN4A SCN7A

Biological processes related to Paramyotonia Congenita according to GeneCards Suite gene sharing:

(show all 11)
id Name GO ID Score Top Affiliating Genes
1 transport GO:0006810 9.67 KCNA1 SCN4A SCN7A
2 ion transport GO:0006811 9.54 KCNA1 SCN4A SCN7A
3 transmembrane transport GO:0055085 9.5 KCNA1 SCN4A SCN7A
4 ion transmembrane transport GO:0034220 9.48 SCN4A SCN7A
5 sodium ion transport GO:0006814 9.46 SCN4A SCN7A
6 muscle contraction GO:0006936 9.43 SCN4A SCN7A
7 sodium ion transmembrane transport GO:0035725 9.4 SCN4A SCN7A
8 regulation of postsynaptic membrane potential GO:0060078 9.26 SCN4A SCN7A
9 membrane depolarization during action potential GO:0086010 9.16 SCN4A SCN7A
10 regulation of ion transmembrane transport GO:0034765 9.13 KCNA1 SCN4A SCN7A
11 neuronal action potential GO:0019228 8.8 KCNA1 SCN4A SCN7A

Molecular functions related to Paramyotonia Congenita according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 sodium channel activity GO:0005272 9.26 SCN4A SCN7A
2 voltage-gated sodium channel activity GO:0005248 9.16 SCN4A SCN7A
3 voltage-gated ion channel activity GO:0005244 9.13 KCNA1 SCN4A SCN7A
4 ion channel activity GO:0005216 8.8 KCNA1 SCN4A SCN7A

Sources for Paramyotonia Congenita

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
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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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