MCAD
MCID: MYT027
MIFTS: 35

Myotonia Congenita, Autosomal Dominant (MCAD)

Categories: Bone diseases, Cardiovascular diseases, Genetic diseases, Muscle diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Myotonia Congenita, Autosomal Dominant

MalaCards integrated aliases for Myotonia Congenita, Autosomal Dominant:

Name: Myotonia Congenita, Autosomal Dominant 56 73 39
Myotonia Levior 73 29 6 71
Myotonia Congenita, Dominant 56 13
Thomsen Disease 56 73
Thd 56 73
Generalized Myotonia of Thomsen 71
Thomsen Disease; Thd 56
Mcad 73

Characteristics:

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
onset in childhood, adolescence
highly variable phenotype and severity
cold temperatures exacerbate symptoms
warm weather and alcohol are alleviating factors
affected females report aggravation of symptoms during menstrual periods and pregnancy, with alleviation after menopause
worldwide prevalence of 1/100,000
increased prevalence in northern finland (7.3/100,000)
see also autosomal recessive form , which is more common and more severe


HPO:

31
myotonia congenita, autosomal dominant:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

OMIM 56 160800
MeSH 43 D009224
SNOMED-CT via HPO 68 16046003 263681008 68962001
UMLS 71 C0270959 C2936781

Summaries for Myotonia Congenita, Autosomal Dominant

UniProtKB/Swiss-Prot : 73 Myotonia congenita, autosomal dominant: A non-dystrophic skeletal muscle disorder characterized by muscle stiffness and an inability of the muscle to relax after voluntary contraction. Most patients have symptom onset in the legs, which later progresses to the arms, neck, and facial muscles. Many patients show marked hypertrophy of the lower limb muscles. The autosomal dominant form (Thomsen disease) is less common and less severe than the autosomal recessive one (Becker disease). A milder form of autosomal dominant myotonia is characterized by isolated myotonia without muscle weakness, hypotrophy, or hypertrophy (myotonia levior).

MalaCards based summary : Myotonia Congenita, Autosomal Dominant, also known as myotonia levior, is related to acyl-coa dehydrogenase, medium-chain, deficiency of and myotonia congenita, and has symptoms including muscular stiffness and lid lag. An important gene associated with Myotonia Congenita, Autosomal Dominant is CLCN1 (Chloride Voltage-Gated Channel 1). Affiliated tissues include skeletal muscle, liver and tongue, and related phenotypes are myalgia and muscle stiffness

OMIM : 56 Autosomal dominant myotonia congenita is a nondystrophic skeletal muscle disorder characterized by muscle stiffness and an inability of the muscle to relax after voluntary contraction (Sun et al., 2001). Thomsen disease is less common and less severe than Becker disease. See also paramyotonia congenita (PMC; 168300) and potassium-aggravated myotonia (608390), overlapping phenotypes caused by mutations in the SCN4A gene (603967). (160800)

Related Diseases for Myotonia Congenita, Autosomal Dominant

Diseases in the Myotonia Congenita family:

Myotonia Congenita, Autosomal Dominant Myotonia Congenita, Autosomal Recessive

Diseases related to Myotonia Congenita, Autosomal Dominant via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 51)
# Related Disease Score Top Affiliating Genes
1 acyl-coa dehydrogenase, medium-chain, deficiency of 12.4
2 myotonia congenita 12.3
3 medium-chain acyl-coenzyme a dehydrogenase deficiency 11.8
4 monoclonal mast cell activation syndrome 11.4
5 myotonia congenita, autosomal recessive 11.4
6 mast cell activation syndrome 11.3
7 segawa syndrome, autosomal recessive 11.3
8 hemorrhoid 10.6
9 acyl-coa dehydrogenase deficiency 10.6
10 hypoglycemia 10.6
11 sudden infant death syndrome 10.5
12 ocular motor apraxia 10.5
13 abdominal obesity-metabolic syndrome 1 10.5
14 phenylketonuria 10.4
15 myotonia 10.4
16 muscle hypertrophy 10.3
17 constipation 10.3
18 internal hemorrhoid 10.3
19 inherited metabolic disorder 10.3
20 autosomal recessive disease 10.3
21 reye syndrome 10.3
22 encephalopathy 10.3
23 alzheimer disease 10.2
24 portal hypertension 10.2
25 thoracic cancer 10.2
26 chronic pain 10.2
27 carbonic anhydrase va deficiency, hyperammonemia due to 10.2
28 encephalopathy, progressive, early-onset, with episodic rhabdomyolysis 10.2
29 congenital hypothyroidism 10.2
30 cardiac arrest 10.2
31 hypothyroidism 10.2
32 hypoglycemic coma 10.2
33 cardiac arrhythmia 10.0
34 intussusception 10.0
35 acyl-coa dehydrogenase, short-chain, deficiency of 10.0
36 lipoid congenital adrenal hyperplasia 10.0
37 cystic fibrosis 10.0
38 galactokinase deficiency 10.0
39 galactosemia 10.0
40 taqi polymorphism 10.0
41 ventricular fibrillation, paroxysmal familial, 1 10.0
42 fatty liver disease, nonalcoholic 1 10.0
43 exanthem 10.0
44 diarrhea 10.0
45 placenta disease 10.0
46 fatty liver disease 10.0
47 sickle cell disease 10.0
48 adrenogenital syndrome 10.0
49 pik3ca-related overgrowth syndrome 10.0
50 acute liver failure 10.0

Graphical network of the top 20 diseases related to Myotonia Congenita, Autosomal Dominant:



Diseases related to Myotonia Congenita, Autosomal Dominant

Symptoms & Phenotypes for Myotonia Congenita, Autosomal Dominant

Human phenotypes related to Myotonia Congenita, Autosomal Dominant:

31 (show all 8)
# Description HPO Frequency HPO Source Accession
1 myalgia 31 occasional (7.5%) HP:0003326
2 muscle stiffness 31 very rare (1%) HP:0003552
3 percussion myotonia 31 very rare (1%) HP:0010548
4 skeletal muscle hypertrophy 31 very rare (1%) HP:0003712
5 myotonia with warm-up phenomenon 31 very rare (1%) HP:0003740
6 handgrip myotonia 31 HP:0012899
7 emg: myotonic runs 31 HP:0003730
8 lid lag on downgaze 31 HP:0025605

Symptoms via clinical synopsis from OMIM:

56
Muscle Soft Tissue:
muscle stiffness
percussion myotonia
handgrip myotonia
myotonia (usually occurs during rapid voluntary muscle movements after a period of rest)
myotonia is most pronounced in the extremities
more
Head And Neck Mouth:
tongue myotonia

Head And Neck Eyes:
lid lag
eyelid myotonia

Clinical features from OMIM:

160800

UMLS symptoms related to Myotonia Congenita, Autosomal Dominant:


muscular stiffness, lid lag

Drugs & Therapeutics for Myotonia Congenita, Autosomal Dominant

Search Clinical Trials , NIH Clinical Center for Myotonia Congenita, Autosomal Dominant

Genetic Tests for Myotonia Congenita, Autosomal Dominant

Genetic tests related to Myotonia Congenita, Autosomal Dominant:

# Genetic test Affiliating Genes
1 Myotonia Levior 29

Anatomical Context for Myotonia Congenita, Autosomal Dominant

MalaCards organs/tissues related to Myotonia Congenita, Autosomal Dominant:

40
Skeletal Muscle, Liver, Tongue, T Cells, Bone, Placenta

Publications for Myotonia Congenita, Autosomal Dominant

Articles related to Myotonia Congenita, Autosomal Dominant:

(show all 31)
# Title Authors PMID Year
1
Myotonia levior is a chloride channel disorder. 61 56 6
7581380 1995
2
Clinical, electrophysiologic, and genetic study of non-dystrophic myotonia in French-Canadians. 56 6
18337100 2009
3
Spectrum of CLCN1 mutations in patients with myotonia congenita in Northern Scandinavia. 56 6
11840191 2001
4
Multimeric structure of ClC-1 chloride channel revealed by mutations in dominant myotonia congenita (Thomsen). 56 6
8112288 1994
5
Molecular basis of Thomsen's disease (autosomal dominant myotonia congenita). 56 6
7981750 1993
6
A novel alteration of muscle chloride channel gating in myotonia levior. 61 6
12456816 2002
7
Myotonia levior: contribution to the nosography. 61 56
3231989 1988
8
EFNS guidelines on the molecular diagnosis of channelopathies, epilepsies, migraine, stroke, and dementias. 6
20298421 2010
9
Cold extends electromyography distinction between ion channel mutations causing myotonia. 56
16786525 2006
10
Myotonia Congenita 6
20301529 2005
11
Decrement of compound muscle action potential is related to mutation type in myotonia congenita. 6
12661046 2003
12
Myotonia caused by mutations in the muscle chloride channel gene CLCN1. 6
11933197 2002
13
Identification of two mutations and a polymorphism in the chloride channel CLCN-1 in patients with Becker's generalized myotonia. 6
10737121 1998
14
A mutation in autosomal dominant myotonia congenita affects pore properties of the muscle chloride channel. 6
9122265 1997
15
Molecular basis for decreased muscle chloride conductance in the myotonic goat. 56
8855341 1996
16
Spectrum of mutations in the major human skeletal muscle chloride channel gene (CLCN1) leading to myotonia. 6
8533761 1995
17
Genetics and physiology of the myotonic muscle disorders. 56
7678441 1993
18
Linkage of Thomsen disease to the T-cell-receptor beta (TCRB) locus on chromosome 7q35. 56
1386711 1992
19
Linkage analysis of candidate loci in autosomal dominant myotonia congenita. 56
1379356 1992
20
The skeletal muscle chloride channel in dominant and recessive human myotonia. 56
1379744 1992
21
Evidence of genetic heterogeneity among the nondystrophic myotonias. 56
1315941 1992
22
Altered sodium channel behaviour causes myotonia in dominantly inherited myotonia congenita. 56
1668369 1991
23
Response to treatment with antihistamines in a family with myotonia congenita. 56
1670657 1991
24
Myotonia congenita (Thomsen's disease) excluded from the region of the myotonic dystrophy locus on chromosome 19. 56
2722193 1989
25
Myotonia congenita with painful muscle contractions. 56
942314 1976
26
A family with dominant hereditary myotonia, muscular hypertrophy, and increased muscular irritability, distinct from myotonia congenita thomsen. 56
1146501 1975
27
Monomelic myopathy. Congenital hypertrophic myotonic myopathy limited to one extremity. 56
6026174 1967
28
Thomsen's disease. Observations on strength-duration curves in myotonia. 56
13941730 1962
29
[Thomsen's myotonia congenita and its differential criterial with other muscular diseases. Study of a family presenting a special grouping of symptoms, in taking special note of the elimination of ribose in the urine]. 56
13751836 1960
30
The treatment of myotonia congenita. 56
14405849 1959
31
[Myotonia levior]. 61
5933347 1966

Variations for Myotonia Congenita, Autosomal Dominant

ClinVar genetic disease variations for Myotonia Congenita, Autosomal Dominant:

6 (show top 50) (show all 162) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 CLCN1 NM_000083.3(CLCN1):c.1488G>T (p.Arg496Ser)SNV Pathogenic 17535 rs121912801 7:143036620-143036620 7:143339527-143339527
2 CLCN1 NM_000083.3(CLCN1):c.1238T>G (p.Phe413Cys)SNV Pathogenic 17531 rs121912799 7:143029583-143029583 7:143332490-143332490
3 CLCN1 NM_000083.3(CLCN1):c.1439C>T (p.Pro480Leu)SNV Pathogenic 17537 rs80356694 7:143036383-143036383 7:143339290-143339290
4 CLCN1 NM_000083.3(CLCN1):c.689G>A (p.Gly230Glu)SNV Pathogenic 17532 rs80356700 7:143018934-143018934 7:143321841-143321841
5 CLCN1 NM_000083.3(CLCN1):c.870C>G (p.Ile290Met)SNV Pathogenic 17539 rs80356690 7:143027881-143027881 7:143330788-143330788
6 CLCN1 NM_000083.3(CLCN1):c.382A>G (p.Met128Val)SNV Pathogenic 17546 rs80356699 7:143017837-143017837 7:143320744-143320744
7 CLCN1 NM_000083.3(CLCN1):c.566C>T (p.Ser189Phe)SNV Pathogenic 17548 rs121912810 7:143018811-143018811 7:143321718-143321718
8 CLCN1 CLCN1, TRP433ARGundetermined variant Pathogenic 17549
9 CLCN1 NM_000083.3(CLCN1):c.1592C>T (p.Ala531Val)SNV Pathogenic 21040 rs80356704 7:143039031-143039031 7:143341938-143341938
10 CLCN1 NM_000083.3(CLCN1):c.920T>C (p.Phe307Ser)SNV Pathogenic 21050 rs80356701 7:143027931-143027931 7:143330838-143330838
11 CLCN1 NM_000083.3(CLCN1):c.937G>A (p.Ala313Thr)SNV Pathogenic 21052 rs80356692 7:143027948-143027948 7:143330855-143330855
12 CLCN1 NM_000083.3(CLCN1):c.1453A>G (p.Met485Val)SNV Pathogenic 280101 rs146457619 7:143036397-143036397 7:143339304-143339304
13 CLCN1 NM_000083.3(CLCN1):c.854G>A (p.Gly285Glu)SNV Pathogenic 280100 rs150885084 7:143027865-143027865 7:143330772-143330772
14 CLCN1 NM_000083.3(CLCN1):c.1437_1450del (p.Pro480fs)deletion Pathogenic 279778 rs768119034 7:143036380-143036393 7:143339287-143339300
15 CLCN1 NM_000083.3(CLCN1):c.180+3A>TSNV Pathogenic 289967 rs202217420 7:143013488-143013488 7:143316395-143316395
16 CLCN1 NM_000083.3(CLCN1):c.2635C>T (p.Gln879Ter)SNV Pathogenic 374131 rs1057518917 7:143048726-143048726 7:143351633-143351633
17 CLCN1 NM_000083.3(CLCN1):c.898_899delinsTA (p.Arg300Ter)indel Pathogenic 447074 rs1554436419 7:143027909-143027910 7:143330816-143330817
18 CLCN1 NM_000083.3(CLCN1):c.1129C>T (p.Arg377Ter)SNV Pathogenic 447045 rs201714423 7:143028708-143028708 7:143331615-143331615
19 CLCN1 NM_000083.3(CLCN1):c.1261dup (p.Arg421fs)duplication Pathogenic 447048 rs763633152 7:143029822-143029823 7:143332729-143332730
20 CLCN1 NM_000083.3(CLCN1):c.1471+1G>ASNV Pathogenic 447052 rs375596425 7:143036416-143036416 7:143339323-143339323
21 CLCN1 NM_000083.3(CLCN1):c.1876C>T (p.Arg626Ter)SNV Pathogenic 447058 rs201894078 7:143039544-143039544 7:143342451-143342451
22 CLCN1 NM_000083.3(CLCN1):c.979G>A (p.Val327Ile)SNV Pathogenic 447078 rs774396430 7:143027990-143027990 7:143330897-143330897
23 CLCN1 NM_000083.3(CLCN1):c.1063G>A (p.Gly355Arg)SNV Pathogenic 447043 rs767000881 7:143028408-143028408 7:143331315-143331315
24 CLCN1 NM_000083.2(CLCN1):c.50_434-202deldeletion Pathogenic 580190 7:143013355-143018256 7:143316262-143321163
25 CLCN1 NM_000083.3(CLCN1):c.1644_1645del (p.Glu548fs)deletion Pathogenic 570543 rs1563084597 7:143039083-143039084 7:143341990-143341991
26 CLCN1 NM_000083.3(CLCN1):c.2172+1G>TSNV Pathogenic 572040 rs1273524525 7:143042856-143042856 7:143345763-143345763
27 CLCN1 NM_000083.3(CLCN1):c.2285-1G>CSNV Pathogenic 573366 rs1222525763 7:143043671-143043671 7:143346578-143346578
28 CLCN1 NM_000083.3(CLCN1):c.2518_2519del (p.Leu840fs)deletion Pathogenic 567845 rs780534566 7:143047670-143047671 7:143350577-143350578
29 CLCN1 NM_000083.3(CLCN1):c.302-1G>ASNV Pathogenic 577893 rs529377088 7:143017756-143017756 7:143320663-143320663
30 CLCN1 NM_000083.3(CLCN1):c.478C>T (p.Gln160Ter)SNV Pathogenic 661766 7:143018502-143018502 7:143321409-143321409
31 CLCN1 NC_000007.13:g.(?_143042594)_(143047767_?)deldeletion Pathogenic 583787 7:143042594-143047767 7:143345501-143350674
32 CLCN1 NM_000083.3(CLCN1):c.751del (p.Ser251fs)deletion Pathogenic 657105 7:143020456-143020456 7:143323363-143323363
33 CLCN1 NM_000083.3(CLCN1):c.789del (p.Ser264fs)deletion Pathogenic 661869 7:143021521-143021521 7:143324428-143324428
34 CLCN1 NM_000083.3(CLCN1):c.1784G>A (p.Trp595Ter)SNV Pathogenic 639175 7:143039223-143039223 7:143342130-143342130
35 CLCN1 NM_000083.3(CLCN1):c.1357del (p.Arg453fs)deletion Pathogenic 648711 7:143029918-143029918 7:143332825-143332825
36 CLCN1 NM_000083.3(CLCN1):c.1357dup (p.Arg453fs)duplication Pathogenic 664719 7:143029917-143029918 7:143332824-143332825
37 CLCN1 NM_000083.3(CLCN1):c.892G>A (p.Ala298Thr)SNV Pathogenic/Likely pathogenic 531747 rs764100025 7:143027903-143027903 7:143330810-143330810
38 CLCN1 NM_000083.3(CLCN1):c.1444G>A (p.Gly482Arg)SNV Pathogenic/Likely pathogenic 546108 rs746125212 7:143036388-143036388 7:143339295-143339295
39 CLCN1 NM_000083.3(CLCN1):c.409T>G (p.Tyr137Asp)SNV Pathogenic/Likely pathogenic 571653 rs748639603 7:143017864-143017864 7:143320771-143320771
40 CLCN1 NM_000083.3(CLCN1):c.1179T>A (p.Tyr393Ter)SNV Pathogenic/Likely pathogenic 489334 rs1554436799 7:143029524-143029524 7:143332431-143332431
41 CLCN1 NM_000083.3(CLCN1):c.2596-1G>ASNV Pathogenic/Likely pathogenic 449534 rs771721648 7:143048686-143048686 7:143351593-143351593
42 CLCN1 NM_000083.2(CLCN1):c.698delG (p.Gly233Alafs)deletion Pathogenic/Likely pathogenic 447069 rs1423567292 7:143020401-143020401 7:143323308-143323308
43 CLCN1 NM_000083.3(CLCN1):c.1012C>T (p.Arg338Ter)SNV Pathogenic/Likely pathogenic 425428 rs759761559 7:143028357-143028357 7:143331264-143331264
44 CLCN1 NM_000083.3(CLCN1):c.2831dup (p.Gly945fs)duplication Pathogenic/Likely pathogenic 280103 rs755176513 7:143048918-143048919 7:143351825-143351826
45 CLCN1 NM_000083.3(CLCN1):c.803C>T (p.Thr268Met)SNV Pathogenic/Likely pathogenic 21047 rs80356687 7:143021535-143021535 7:143324442-143324442
46 CLCN1 NM_000083.3(CLCN1):c.1013G>A (p.Arg338Gln)SNV Pathogenic/Likely pathogenic 21037 rs80356703 7:143028358-143028358 7:143331265-143331265
47 CLCN1 NM_000083.3(CLCN1):c.950G>A (p.Arg317Gln)SNV Pathogenic/Likely pathogenic 17542 rs80356702 7:143027961-143027961 7:143330868-143330868
48 CLCN1 NM_000083.3(CLCN1):c.2680C>T (p.Arg894Ter)SNV Pathogenic/Likely pathogenic 17545 rs55960271 7:143048771-143048771 7:143351678-143351678
49 CLCN1 NM_000083.3(CLCN1):c.1655A>G (p.Gln552Arg)SNV Pathogenic/Likely pathogenic 17538 rs80356696 7:143039094-143039094 7:143342001-143342001
50 CLCN1 NM_000083.3(CLCN1):c.1649C>T (p.Thr550Met)SNV Likely pathogenic 208084 rs762754992 7:143039088-143039088 7:143341995-143341995

UniProtKB/Swiss-Prot genetic disease variations for Myotonia Congenita, Autosomal Dominant:

73 (show all 17)
# Symbol AA change Variation ID SNP ID
1 CLCN1 p.Phe161Val VAR_001586
2 CLCN1 p.Gly200Arg VAR_001589
3 CLCN1 p.Gly230Glu VAR_001590 rs80356700
4 CLCN1 p.Val286Ala VAR_001594 rs80356689
5 CLCN1 p.Ile290Met VAR_001595 rs80356690
6 CLCN1 p.Phe307Ser VAR_001598 rs80356701
7 CLCN1 p.Ala313Thr VAR_001599 rs80356692
8 CLCN1 p.Arg317Gln VAR_001600 rs80356702
9 CLCN1 p.Arg338Gln VAR_001603 rs80356703
10 CLCN1 p.Pro480Leu VAR_001607 rs80356694
11 CLCN1 p.Gln552Arg VAR_001611 rs80356696
12 CLCN1 p.Ile556Asn VAR_001612 rs80356697
13 CLCN1 p.Met128Val VAR_075591 rs80356699
14 CLCN1 p.Glu193Lys VAR_075597 rs80356686
15 CLCN1 p.Leu198Pro VAR_075599
16 CLCN1 p.Phe484Leu VAR_075605 rs131200284
17 CLCN1 p.Pro480His VAR_077244

Expression for Myotonia Congenita, Autosomal Dominant

Search GEO for disease gene expression data for Myotonia Congenita, Autosomal Dominant.

Pathways for Myotonia Congenita, Autosomal Dominant

GO Terms for Myotonia Congenita, Autosomal Dominant

Sources for Myotonia Congenita, Autosomal Dominant

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57 OMIM via Orphanet
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68 SNOMED-CT via HPO
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72 UMLS via Orphanet
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