MCID: PRM057
MIFTS: 34

Paramyotonia Congenita of Von Eulenburg

Categories: Genetic diseases, Rare diseases, Neuronal diseases

Aliases & Classifications for Paramyotonia Congenita of Von Eulenburg

MalaCards integrated aliases for Paramyotonia Congenita of Von Eulenburg:

Name: Paramyotonia Congenita of Von Eulenburg 57 76 53 25 59 75 29 6 40
Paramyotonia Congenita 57 76 53 25 59 37 13 55 73
Pmc 57 53 25 75
Paralysis Periodica Paramyotonica 57 53 75
Paralysis Periodica Paramyotonia 25 75
Eulenburg Disease 53 25
Paramyotonia Congenita Without Cold Paralysis 75
Von Eulenburg Paramyotonia Congenita 53
Myotonia Congenita Intermittens 53
Von Eulenberg's Disease 25

Characteristics:

Orphanet epidemiological data:

59
paramyotonia congenita of von eulenburg
Inheritance: Autosomal dominant; Age of onset: Adolescent,Adult,Childhood;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
highly variable phenotype
onset in infancy or early childhood
affected females report aggravation of symptoms during menstrual periods and pregnancy, with alleviation after menopause
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 )
allelic disorder to hyperkalemic periodic paralysis (hypp, )
allelic disorder to potassium-aggravated myotonia
allelic disorder to hypokalemic periodic paralysis (hokpp, )


HPO:

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


Classifications:

Orphanet: 59  
Rare neurological diseases


External Ids:

OMIM 57 168300
Orphanet 59 ORPHA684
MESH via Orphanet 45 C538616
ICD10 via Orphanet 34 G71.1
UMLS via Orphanet 74 C1868617 C0221055
MeSH 44 D020967
KEGG 37 H00743

Summaries for Paramyotonia Congenita of Von Eulenburg

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 of Von Eulenburg, also known as paramyotonia congenita, is related to myotonia and myotonia congenita, autosomal dominant, and has symptoms including muscular stiffness and myalgia. An important gene associated with Paramyotonia Congenita of Von Eulenburg is SCN4A (Sodium Voltage-Gated Channel Alpha Subunit 4). The drugs Dichlorphenamide and Mexiletine have been mentioned in the context of this disorder. Affiliated tissues include skeletal muscle and tongue, and related phenotypes are neonatal hypotonia and muscle weakness

NIH Rare Diseases : 53 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.

UniProtKB/Swiss-Prot : 75 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 : 76 Paramyotonia congenita (PC), also known as paramyotonia congenita of von Eulenburg or Eulenburg disease,... more...

Description from OMIM: 168300

Related Diseases for Paramyotonia Congenita of Von Eulenburg

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

(show all 11)
# Related Disease Score Top Affiliating Genes
1 myotonia 29.1 LOC105371858 SCN4A
2 myotonia congenita, autosomal dominant 10.9
3 ovarian cancer 9.9
4 scleroderma, familial progressive 9.9
5 brain ischemia 9.9
6 hepatitis 9.9
7 ischemia 9.9
8 lupus erythematosus 9.9
9 normokalemic periodic paralysis 9.4 LOC105371858 SCN4A
10 hypokalemic periodic paralysis, type 2 9.3 LOC105371858 SCN4A
11 congenital myasthenic syndrome 9.0 LOC105371858 SCN4A

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



Diseases related to Paramyotonia Congenita of Von Eulenburg

Symptoms & Phenotypes for Paramyotonia Congenita of Von Eulenburg

Symptoms via clinical synopsis from OMIM:

57
Muscle Soft Tissue:
muscle stiffness
percussion myotonia
muscle pain
muscle hypertrophy
myotonia, cold-sensitive, predominantly of face, tongue, forearm, and hand precipitated by muscle cooling or cold exposure or rest after exercise
more
Abdomen Gastrointestinal:
poor feeding in early life

Respiratory:
inspiratory stridor in early life


Clinical features from OMIM:

168300

Human phenotypes related to Paramyotonia Congenita of Von Eulenburg:

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

UMLS symptoms related to Paramyotonia Congenita of Von Eulenburg:


muscular stiffness, myalgia

Drugs & Therapeutics for Paramyotonia Congenita of Von Eulenburg

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

(show all 15)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Dichlorphenamide Approved, Investigational Phase 3 120-97-8 3038
2
Mexiletine Approved, Investigational 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
Ranolazine Approved, Investigational Phase 2 142387-99-3, 95635-55-5 56959
15
Lidocaine Approved, Vet_approved Phase 2 137-58-6 3676

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

Search NIH Clinical Center for Paramyotonia Congenita of Von Eulenburg

Genetic Tests for Paramyotonia Congenita of Von Eulenburg

Genetic tests related to Paramyotonia Congenita of Von Eulenburg:

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

Anatomical Context for Paramyotonia Congenita of Von Eulenburg

MalaCards organs/tissues related to Paramyotonia Congenita of Von Eulenburg:

41
Skeletal Muscle, Tongue

Publications for Paramyotonia Congenita of Von Eulenburg

Articles related to Paramyotonia Congenita of Von Eulenburg:

# Title Authors Year
1
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

Variations for Paramyotonia Congenita of Von Eulenburg

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

75 (show all 20)
# 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 of Von Eulenburg:

6
(show top 50) (show all 252)
# 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.4342C> T (p.Arg1448Cys) single nucleotide variant Pathogenic rs121908544 GRCh38 Chromosome 17, 63941940: 63941940
3 SCN4A NM_000334.4(SCN4A): c.4343G> A (p.Arg1448His) single nucleotide variant Pathogenic rs121908545 GRCh37 Chromosome 17, 62019299: 62019299
4 SCN4A NM_000334.4(SCN4A): c.4343G> A (p.Arg1448His) single nucleotide variant Pathogenic rs121908545 GRCh38 Chromosome 17, 63941939: 63941939
5 SCN4A NM_000334.4(SCN4A): c.3917G> T (p.Gly1306Val) single nucleotide variant Pathogenic rs80338792 GRCh37 Chromosome 17, 62021206: 62021206
6 SCN4A NM_000334.4(SCN4A): c.3917G> T (p.Gly1306Val) single nucleotide variant Pathogenic rs80338792 GRCh38 Chromosome 17, 63943846: 63943846
7 SCN4A NM_000334.4(SCN4A): c.3938C> T (p.Thr1313Met) single nucleotide variant Pathogenic rs121908547 GRCh37 Chromosome 17, 62021185: 62021185
8 SCN4A NM_000334.4(SCN4A): c.3938C> T (p.Thr1313Met) single nucleotide variant Pathogenic rs121908547 GRCh38 Chromosome 17, 63943825: 63943825
9 SCN4A NM_000334.4(SCN4A): c.4765G> A (p.Val1589Met) single nucleotide variant Pathogenic rs121908548 GRCh37 Chromosome 17, 62018877: 62018877
10 SCN4A NM_000334.4(SCN4A): c.4765G> A (p.Val1589Met) single nucleotide variant Pathogenic rs121908548 GRCh38 Chromosome 17, 63941517: 63941517
11 SCN4A NM_000334.4(SCN4A): c.4298T> G (p.Leu1433Arg) single nucleotide variant Pathogenic rs121908550 GRCh37 Chromosome 17, 62019344: 62019344
12 SCN4A NM_000334.4(SCN4A): c.4298T> G (p.Leu1433Arg) single nucleotide variant Pathogenic rs121908550 GRCh38 Chromosome 17, 63941984: 63941984
13 SCN4A NM_000334.4(SCN4A): c.3917G> C (p.Gly1306Ala) single nucleotide variant Pathogenic rs80338792 GRCh37 Chromosome 17, 62021206: 62021206
14 SCN4A NM_000334.4(SCN4A): c.3917G> C (p.Gly1306Ala) single nucleotide variant Pathogenic rs80338792 GRCh38 Chromosome 17, 63943846: 63943846
15 SCN4A NM_000334.4(SCN4A): c.3877G> A (p.Val1293Ile) single nucleotide variant Pathogenic rs121908551 GRCh37 Chromosome 17, 62022068: 62022068
16 SCN4A NM_000334.4(SCN4A): c.3877G> A (p.Val1293Ile) single nucleotide variant Pathogenic rs121908551 GRCh38 Chromosome 17, 63944708: 63944708
17 SCN4A NM_000334.4(SCN4A): c.4367G> A (p.Gly1456Glu) single nucleotide variant Pathogenic rs121908554 GRCh37 Chromosome 17, 62019275: 62019275
18 SCN4A NM_000334.4(SCN4A): c.4367G> A (p.Gly1456Glu) single nucleotide variant Pathogenic rs121908554 GRCh38 Chromosome 17, 63941915: 63941915
19 SCN4A NM_000334.4(SCN4A): c.4428G> A (p.Met1476Ile) single nucleotide variant Pathogenic rs121908559 GRCh37 Chromosome 17, 62019214: 62019214
20 SCN4A NM_000334.4(SCN4A): c.4428G> A (p.Met1476Ile) single nucleotide variant Pathogenic rs121908559 GRCh38 Chromosome 17, 63941854: 63941854
21 SCN4A NM_000334.4(SCN4A): c.2078T> C (p.Ile693Thr) single nucleotide variant Pathogenic rs80338956 GRCh37 Chromosome 17, 62034820: 62034820
22 SCN4A NM_000334.4(SCN4A): c.2078T> C (p.Ile693Thr) single nucleotide variant Pathogenic rs80338956 GRCh38 Chromosome 17, 63957460: 63957460
23 SCN4A NM_000334.4(SCN4A): c.421A> G (p.Ile141Val) single nucleotide variant Pathogenic rs121908561 GRCh37 Chromosome 17, 62049557: 62049557
24 SCN4A NM_000334.4(SCN4A): c.421A> G (p.Ile141Val) single nucleotide variant Pathogenic rs121908561 GRCh38 Chromosome 17, 63972197: 63972197
25 SCN4A NM_000334.4(SCN4A): c.3318+12C> A single nucleotide variant Benign rs13341114 GRCh37 Chromosome 17, 62025238: 62025238
26 SCN4A NM_000334.4(SCN4A): c.3318+12C> A single nucleotide variant Benign rs13341114 GRCh38 Chromosome 17, 63947878: 63947878
27 SCN4A NM_000334.4(SCN4A): c.2478C> T (p.Ile826=) single nucleotide variant Conflicting interpretations of pathogenicity rs371914255 GRCh37 Chromosome 17, 62029159: 62029159
28 SCN4A NM_000334.4(SCN4A): c.2478C> T (p.Ile826=) single nucleotide variant Conflicting interpretations of pathogenicity rs371914255 GRCh38 Chromosome 17, 63951799: 63951799
29 SCN4A NM_000334.4(SCN4A): c.4690G> A (p.Val1564Ile) single nucleotide variant Conflicting interpretations of pathogenicity rs202106192 GRCh37 Chromosome 17, 62018952: 62018952
30 SCN4A NM_000334.4(SCN4A): c.4690G> A (p.Val1564Ile) single nucleotide variant Conflicting interpretations of pathogenicity rs202106192 GRCh38 Chromosome 17, 63941592: 63941592
31 SCN4A NM_000334.4(SCN4A): c.553G> A (p.Asp185Asn) single nucleotide variant Uncertain significance rs778661227 GRCh37 Chromosome 17, 62049140: 62049140
32 SCN4A NM_000334.4(SCN4A): c.553G> A (p.Asp185Asn) single nucleotide variant Uncertain significance rs778661227 GRCh38 Chromosome 17, 63971780: 63971780
33 SCN4A NM_000334.4(SCN4A): c.952T> C (p.Trp318Arg) single nucleotide variant Conflicting interpretations of pathogenicity rs199676994 GRCh37 Chromosome 17, 62045467: 62045467
34 SCN4A NM_000334.4(SCN4A): c.952T> C (p.Trp318Arg) single nucleotide variant Conflicting interpretations of pathogenicity rs199676994 GRCh38 Chromosome 17, 63968107: 63968107
35 SCN4A NM_000334.4(SCN4A): c.4215C> T (p.Leu1405=) single nucleotide variant Benign/Likely benign rs141215137 GRCh38 Chromosome 17, 63942899: 63942899
36 SCN4A NM_000334.4(SCN4A): c.4215C> T (p.Leu1405=) single nucleotide variant Benign/Likely benign rs141215137 GRCh37 Chromosome 17, 62020259: 62020259
37 SCN4A NM_000334.4(SCN4A): c.4125C> T (p.Asp1375=) single nucleotide variant Uncertain significance rs375607705 GRCh37 Chromosome 17, 62020349: 62020349
38 SCN4A NM_000334.4(SCN4A): c.4125C> T (p.Asp1375=) single nucleotide variant Uncertain significance rs375607705 GRCh38 Chromosome 17, 63942989: 63942989
39 SCN4A NM_000334.4(SCN4A): c.4017+15G> T single nucleotide variant Benign/Likely benign rs77844100 GRCh38 Chromosome 17, 63943731: 63943731
40 SCN4A NM_000334.4(SCN4A): c.4017+15G> T single nucleotide variant Benign/Likely benign rs77844100 GRCh37 Chromosome 17, 62021091: 62021091
41 SCN4A NM_000334.4(SCN4A): c.3720+10A> G single nucleotide variant Benign/Likely benign rs111679484 GRCh38 Chromosome 17, 63945350: 63945350
42 SCN4A NM_000334.4(SCN4A): c.3720+10A> G single nucleotide variant Benign/Likely benign rs111679484 GRCh37 Chromosome 17, 62022710: 62022710
43 SCN4A NM_000334.4(SCN4A): c.2722G> A (p.Glu908Lys) single nucleotide variant Benign/Likely benign rs117664682 GRCh37 Chromosome 17, 62028915: 62028915
44 SCN4A NM_000334.4(SCN4A): c.2722G> A (p.Glu908Lys) single nucleotide variant Benign/Likely benign rs117664682 GRCh38 Chromosome 17, 63951555: 63951555
45 SCN4A NM_000334.4(SCN4A): c.1100+7G> A single nucleotide variant Conflicting interpretations of pathogenicity rs200770684 GRCh38 Chromosome 17, 63966474: 63966474
46 SCN4A NM_000334.4(SCN4A): c.1100+7G> A single nucleotide variant Conflicting interpretations of pathogenicity rs200770684 GRCh37 Chromosome 17, 62043834: 62043834
47 SCN4A NM_000334.4(SCN4A): c.726C> T (p.Ala242=) single nucleotide variant Benign/Likely benign rs73326368 GRCh38 Chromosome 17, 63968333: 63968333
48 SCN4A NM_000334.4(SCN4A): c.726C> T (p.Ala242=) single nucleotide variant Benign/Likely benign rs73326368 GRCh37 Chromosome 17, 62045693: 62045693
49 SCN4A NM_000334.4(SCN4A): c.489C> G (p.Thr163=) single nucleotide variant Benign/Likely benign rs146590697 GRCh38 Chromosome 17, 63971844: 63971844
50 SCN4A NM_000334.4(SCN4A): c.489C> G (p.Thr163=) single nucleotide variant Benign/Likely benign rs146590697 GRCh37 Chromosome 17, 62049204: 62049204

Expression for Paramyotonia Congenita of Von Eulenburg

Search GEO for disease gene expression data for Paramyotonia Congenita of Von Eulenburg.

Pathways for Paramyotonia Congenita of Von Eulenburg

GO Terms for Paramyotonia Congenita of Von Eulenburg

Sources for Paramyotonia Congenita of Von Eulenburg

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 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 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
Content
Loading form....