CMS2A
MCID: MYS062
MIFTS: 28

Myasthenic Syndrome, Congenital, 2a, Slow-Channel (CMS2A)

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

Aliases & Classifications for Myasthenic Syndrome, Congenital, 2a, Slow-Channel

MalaCards integrated aliases for Myasthenic Syndrome, Congenital, 2a, Slow-Channel:

Name: Myasthenic Syndrome, Congenital, 2a, Slow-Channel 57 72 29 6
Cms2a 57 72
Myasthenic Syndrome, Congenital, Postsynaptic Slow-Channel 70
Myasthenic Syndrome, Congenital, Type 2a, Slow-Channel 39

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal dominant

Miscellaneous:
onset at birth
two unrelated patients have been reported (last curated april 2015)


HPO:

31
myasthenic syndrome, congenital, 2a, slow-channel:
Inheritance autosomal dominant inheritance
Onset and clinical course congenital onset


Classifications:



Summaries for Myasthenic Syndrome, Congenital, 2a, Slow-Channel

UniProtKB/Swiss-Prot : 72 Myasthenic syndrome, congenital, 2A, slow-channel: A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre- synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS2A is a slow-channel myasthenic syndrome. It is caused by kinetic abnormalities of the AChR, resulting in prolonged AChR channel opening episodes, prolonged endplate currents, and depolarization block. This is associated with calcium overload, which may contribute to subsequent degeneration of the endplate and postsynaptic membrane.

MalaCards based summary : Myasthenic Syndrome, Congenital, 2a, Slow-Channel, also known as cms2a, is related to myasthenic syndrome, congenital, 1a, slow-channel and slow-channel congenital myasthenic syndrome. An important gene associated with Myasthenic Syndrome, Congenital, 2a, Slow-Channel is CHRNB1 (Cholinergic Receptor Nicotinic Beta 1 Subunit). Affiliated tissues include skeletal muscle, and related phenotypes are flexion contracture and ptosis

OMIM® : 57 Slow-channel congenital myasthenic syndrome (SCCMS) is a disorder of the postsynaptic neuromuscular junction (NMJ) characterized by early-onset progressive muscle weakness. The disorder results from kinetic abnormalities of the acetylcholine receptor channel, specifically from prolonged opening and activity of the channel, which causes prolonged synaptic currents resulting in a depolarization block. This is associated with calcium overload, which may contribute to subsequent degeneration of the endplate and postsynaptic membrane. Treatment with quinine, quinidine, or fluoxetine may be helpful; cholinesterase inhibitors and amifampridine should be avoided (summary by Engel et al., 2015). For a discussion of genetic heterogeneity of CMS, see CMS1A (601462). (616313) (Updated 05-Apr-2021)

Related Diseases for Myasthenic Syndrome, Congenital, 2a, Slow-Channel

Diseases in the Slow-Channel Congenital Myasthenic Syndrome family:

Myasthenic Syndrome, Congenital, 1a, Slow-Channel Myasthenic Syndrome, Congenital, 4a, Slow-Channel
Myasthenic Syndrome, Congenital, 2a, Slow-Channel Myasthenic Syndrome, Congenital, 3a, Slow-Channel

Diseases related to Myasthenic Syndrome, Congenital, 2a, Slow-Channel via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 myasthenic syndrome, congenital, 1a, slow-channel 11.3
2 slow-channel congenital myasthenic syndrome 11.0

Symptoms & Phenotypes for Myasthenic Syndrome, Congenital, 2a, Slow-Channel

Human phenotypes related to Myasthenic Syndrome, Congenital, 2a, Slow-Channel:

31 (show all 11)
# Description HPO Frequency HPO Source Accession
1 flexion contracture 31 occasional (7.5%) HP:0001371
2 ptosis 31 HP:0000508
3 facial palsy 31 HP:0010628
4 high palate 31 HP:0000218
5 neonatal hypotonia 31 HP:0001319
6 myopathy 31 HP:0003198
7 skeletal muscle atrophy 31 HP:0003202
8 easy fatigability 31 HP:0003388
9 ophthalmoplegia 31 HP:0000602
10 narrow face 31 HP:0000275
11 long face 31 HP:0000276

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Head And Neck Eyes:
ptosis
ophthalmoplegia

Head And Neck Face:
long face
facial muscle weakness
thin face

Skeletal:
joint contractures (in some patients)

Growth Other:
small body habitus

Muscle Soft Tissue:
easy fatigability
muscle atrophy
hypotonia, neonatal
endplate myopathy
decremental response to repetitive nerve stimulation
more
Head And Neck Mouth:
high-arched palate

Neurologic Central Nervous System:
delayed motor development due to muscle weakness

Clinical features from OMIM®:

616313 (Updated 05-Apr-2021)

Drugs & Therapeutics for Myasthenic Syndrome, Congenital, 2a, Slow-Channel

Search Clinical Trials , NIH Clinical Center for Myasthenic Syndrome, Congenital, 2a, Slow-Channel

Genetic Tests for Myasthenic Syndrome, Congenital, 2a, Slow-Channel

Genetic tests related to Myasthenic Syndrome, Congenital, 2a, Slow-Channel:

# Genetic test Affiliating Genes
1 Myasthenic Syndrome, Congenital, 2a, Slow-Channel 29 CHRNB1

Anatomical Context for Myasthenic Syndrome, Congenital, 2a, Slow-Channel

MalaCards organs/tissues related to Myasthenic Syndrome, Congenital, 2a, Slow-Channel:

40
Skeletal Muscle

Publications for Myasthenic Syndrome, Congenital, 2a, Slow-Channel

Articles related to Myasthenic Syndrome, Congenital, 2a, Slow-Channel:

# Title Authors PMID Year
1
New mutations in acetylcholine receptor subunit genes reveal heterogeneity in the slow-channel congenital myasthenic syndrome. 6 57
8872460 1996
2
A beta-subunit mutation in the acetylcholine receptor channel gate causes severe slow-channel syndrome. 6 57
8651643 1996
3
Mutations Causing Slow-Channel Myasthenia Reveal That a Valine Ring in the Channel Pore of Muscle AChR is Optimized for Stabilizing Channel Gating. 6
27375219 2016
4
Whole exome sequencing diagnosis of inborn errors of metabolism and other disorders in United Arab Emirates. 6
27391121 2016
5
Congenital myasthenic syndromes: pathogenesis, diagnosis, and treatment. 57
25792100 2015
6
Molecular characterisation of congenital myasthenic syndromes in Southern Brazil. 6
20562457 2010
7
Mutation causing congenital myasthenia reveals acetylcholine receptor beta/delta subunit interaction essential for assembly. 6
10562302 1999
8
Combining multiple laser scans of spotted microarrays by means of a two-way ANOVA model. 61
22499702 2012

Variations for Myasthenic Syndrome, Congenital, 2a, Slow-Channel

ClinVar genetic disease variations for Myasthenic Syndrome, Congenital, 2a, Slow-Channel:

6 (show top 50) (show all 112)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 CHRNB1 NM_000747.3(CHRNB1):c.865G>A (p.Val289Met) SNV Pathogenic 18372 rs137852810 GRCh37: 17:7357660-7357660
GRCh38: 17:7454341-7454341
2 CHRNB1 NM_000747.3(CHRNB1):c.853C>A (p.Leu285Met) SNV Pathogenic 18373 rs137852811 GRCh37: 17:7357648-7357648
GRCh38: 17:7454329-7454329
3 CHRNB1 NM_000747.3(CHRNB1):c.516C>G (p.Tyr172Ter) SNV Pathogenic 476151 rs201033437 GRCh37: 17:7350875-7350875
GRCh38: 17:7447556-7447556
4 CHRNB1 NM_000747.3(CHRNB1):c.248G>A (p.Trp83Ter) SNV Pathogenic 569774 rs766823872 GRCh37: 17:7350156-7350156
GRCh38: 17:7446837-7446837
5 CHRNB1 NC_000017.11:g.(?_7454277)_(7454540_?)del Deletion Pathogenic 584314 GRCh37: 17:7357596-7357859
GRCh38: 17:7454277-7454540
6 CHRNB1 NC_000017.11:g.(?_7454287)_(7454530_?)del Deletion Pathogenic 651814 GRCh37: 17:7357606-7357849
GRCh38: 17:7454287-7454530
7 CHRNB1 NM_000747.3(CHRNB1):c.866T>C (p.Val289Ala) SNV Pathogenic 860460 GRCh37: 17:7357661-7357661
GRCh38: 17:7454342-7454342
8 CHRNB1 NM_000747.3(CHRNB1):c.354-1G>A SNV Likely pathogenic 661296 rs1597749210 GRCh37: 17:7350361-7350361
GRCh38: 17:7447042-7447042
9 CHRNB1 NM_000747.3(CHRNB1):c.687_688insT (p.Gly230fs) Insertion Likely pathogenic 930319 GRCh37: 17:7351974-7351975
GRCh38: 17:7448655-7448656
10 CHRNB1 NM_000747.3(CHRNB1):c.686_687insGGG (p.Gly230dup) Insertion Uncertain significance 930320 GRCh37: 17:7351973-7351974
GRCh38: 17:7448654-7448655
11 CHRNB1 NM_000747.3(CHRNB1):c.1177C>G (p.Arg393Gly) SNV Uncertain significance 938548 GRCh37: 17:7358735-7358735
GRCh38: 17:7455416-7455416
12 CHRNB1 NM_000747.3(CHRNB1):c.793T>G (p.Phe265Val) SNV Uncertain significance 945110 GRCh37: 17:7352080-7352080
GRCh38: 17:7448761-7448761
13 CHRNB1 NM_000747.3(CHRNB1):c.898G>C (p.Glu300Gln) SNV Uncertain significance 948769 GRCh37: 17:7357693-7357693
GRCh38: 17:7454374-7454374
14 CHRNB1 NM_000747.3(CHRNB1):c.61G>A (p.Val21Ile) SNV Uncertain significance 954440 GRCh37: 17:7348591-7348591
GRCh38: 17:7445272-7445272
15 CHRNB1 NM_000747.3(CHRNB1):c.347T>C (p.Leu116Pro) SNV Uncertain significance 957111 GRCh37: 17:7350255-7350255
GRCh38: 17:7446936-7446936
16 CHRNB1 NM_000747.3(CHRNB1):c.31G>A (p.Gly11Arg) SNV Uncertain significance 964055 GRCh37: 17:7348477-7348477
GRCh38: 17:7445158-7445158
17 CHRNB1 NC_000017.10:g.(?_7348427)_(7352127_?)dup Duplication Uncertain significance 999130 GRCh37: 17:7348427-7352127
GRCh38:
18 CHRNB1 NM_000747.3(CHRNB1):c.304C>T (p.Arg102Cys) SNV Uncertain significance 1003394 GRCh37: 17:7350212-7350212
GRCh38: 17:7446893-7446893
19 CHRNB1 NM_000747.3(CHRNB1):c.214G>A (p.Glu72Lys) SNV Uncertain significance 1007600 GRCh37: 17:7349403-7349403
GRCh38: 17:7446084-7446084
20 CHRNB1 NM_000747.3(CHRNB1):c.286G>T (p.Asp96Tyr) SNV Uncertain significance 1011016 GRCh37: 17:7350194-7350194
GRCh38: 17:7446875-7446875
21 CHRNB1 NM_000747.3(CHRNB1):c.167T>C (p.Val56Ala) SNV Uncertain significance 523042 rs759668768 GRCh37: 17:7348697-7348697
GRCh38: 17:7445378-7445378
22 CHRNB1 NM_000747.3(CHRNB1):c.725G>T (p.Arg242Leu) SNV Uncertain significance 835831 GRCh37: 17:7352012-7352012
GRCh38: 17:7448693-7448693
23 CHRNB1 NM_000747.3(CHRNB1):c.608T>C (p.Ile203Thr) SNV Uncertain significance 845718 GRCh37: 17:7350967-7350967
GRCh38: 17:7447648-7447648
24 CHRNB1 NM_000747.3(CHRNB1):c.1026G>A (p.Met342Ile) SNV Uncertain significance 860888 GRCh37: 17:7357821-7357821
GRCh38: 17:7454502-7454502
25 CHRNB1 NM_000747.3(CHRNB1):c.1441G>T (p.Val481Phe) SNV Uncertain significance 945710 GRCh37: 17:7359977-7359977
GRCh38: 17:7456658-7456658
26 CHRNB1 NM_000747.3(CHRNB1):c.236T>C (p.Leu79Ser) SNV Uncertain significance 890187 GRCh37: 17:7349425-7349425
GRCh38: 17:7446106-7446106
27 CHRNB1 NM_000747.3(CHRNB1):c.1146C>G (p.Gly382=) SNV Uncertain significance 325105 rs886053403 GRCh37: 17:7358704-7358704
GRCh38: 17:7455385-7455385
28 CHRNB1 NM_000747.3(CHRNB1):c.1364C>A (p.Ala455Glu) SNV Uncertain significance 1016707 GRCh37: 17:7359259-7359259
GRCh38: 17:7455940-7455940
29 CHRNB1 NM_000747.3(CHRNB1):c.472T>C (p.Phe158Leu) SNV Uncertain significance 1021952 GRCh37: 17:7350831-7350831
GRCh38: 17:7447512-7447512
30 CHRNB1 NM_000747.3(CHRNB1):c.982G>A (p.Val328Met) SNV Uncertain significance 1023571 GRCh37: 17:7357777-7357777
GRCh38: 17:7454458-7454458
31 CHRNB1 NM_000747.3(CHRNB1):c.775A>T (p.Ile259Phe) SNV Uncertain significance 1024802 GRCh37: 17:7352062-7352062
GRCh38: 17:7448743-7448743
32 CHRNB1 NM_000747.3(CHRNB1):c.343C>G (p.Leu115Val) SNV Uncertain significance 1026787 GRCh37: 17:7350251-7350251
GRCh38: 17:7446932-7446932
33 CHRNB1 NM_000747.3(CHRNB1):c.914T>G (p.Val305Gly) SNV Uncertain significance 639222 rs372910299 GRCh37: 17:7357709-7357709
GRCh38: 17:7454390-7454390
34 CHRNB1 NM_000747.3(CHRNB1):c.1292del (p.Pro431fs) Deletion Uncertain significance 647770 rs1239393228 GRCh37: 17:7359186-7359186
GRCh38: 17:7455867-7455867
35 CHRNB1 NM_000747.3(CHRNB1):c.956T>C (p.Val319Ala) SNV Uncertain significance 850367 GRCh37: 17:7357751-7357751
GRCh38: 17:7454432-7454432
36 CHRNB1 NM_000747.3(CHRNB1):c.462+6C>T SNV Uncertain significance 858008 GRCh37: 17:7350476-7350476
GRCh38: 17:7447157-7447157
37 CHRNB1 NM_000747.3(CHRNB1):c.1365+5del Deletion Uncertain significance 946084 GRCh37: 17:7359265-7359265
GRCh38: 17:7455946-7455946
38 CHRNB1 NM_000747.3(CHRNB1):c.354-8C>G SNV Uncertain significance 956745 GRCh37: 17:7350354-7350354
GRCh38: 17:7447035-7447035
39 CHRNB1 NM_000747.3(CHRNB1):c.302T>C (p.Leu101Pro) SNV Uncertain significance 1034600 GRCh37: 17:7350210-7350210
GRCh38: 17:7446891-7446891
40 CHRNB1 NM_000747.3(CHRNB1):c.631A>G (p.Ile211Val) SNV Uncertain significance 1035866 GRCh37: 17:7351918-7351918
GRCh38: 17:7448599-7448599
41 CHRNB1 NM_000747.3(CHRNB1):c.801C>G (p.Phe267Leu) SNV Uncertain significance 1036396 GRCh37: 17:7352088-7352088
GRCh38: 17:7448769-7448769
42 CHRNB1 NM_000747.3(CHRNB1):c.185A>C (p.Gln62Pro) SNV Uncertain significance 1045635 GRCh37: 17:7348715-7348715
GRCh38: 17:7445396-7445396
43 CHRNB1 NM_000747.3(CHRNB1):c.44C>T (p.Ala15Val) SNV Uncertain significance 655540 rs75926342 GRCh37: 17:7348490-7348490
GRCh38: 17:7445171-7445171
44 CHRNB1 NC_000017.10:g.(?_7348427)_(7352127_?)dup Duplication Uncertain significance 658985 GRCh37: 17:7348427-7352127
GRCh38: 17:7445108-7448808
45 CHRNB1 NM_000747.3(CHRNB1):c.1406G>T (p.Arg469Leu) SNV Uncertain significance 659479 rs762250406 GRCh37: 17:7359942-7359942
GRCh38: 17:7456623-7456623
46 CHRNB1 NM_000747.3(CHRNB1):c.314C>T (p.Ala105Val) SNV Uncertain significance 659989 rs866965972 GRCh37: 17:7350222-7350222
GRCh38: 17:7446903-7446903
47 CHRNB1 NM_000747.3(CHRNB1):c.1321A>G (p.Ser441Gly) SNV Uncertain significance 660971 rs754895386 GRCh37: 17:7359216-7359216
GRCh38: 17:7455897-7455897
48 CHRNB1 NM_000747.3(CHRNB1):c.909A>G (p.Leu303=) SNV Uncertain significance 641208 rs774773039 GRCh37: 17:7357704-7357704
GRCh38: 17:7454385-7454385
49 CHRNB1 NM_000747.3(CHRNB1):c.808C>A (p.Pro270Thr) SNV Uncertain significance 641587 rs749302262 GRCh37: 17:7352095-7352095
GRCh38: 17:7448776-7448776
50 CHRNB1 NM_000747.3(CHRNB1):c.240C>G (p.Asp80Glu) SNV Uncertain significance 642218 rs373533921 GRCh37: 17:7349429-7349429
GRCh38: 17:7446110-7446110

UniProtKB/Swiss-Prot genetic disease variations for Myasthenic Syndrome, Congenital, 2a, Slow-Channel:

72
# Symbol AA change Variation ID SNP ID
1 CHRNB1 p.Leu285Met VAR_000287 rs137852811
2 CHRNB1 p.Val289Met VAR_000288 rs137852810
3 CHRNB1 p.Val289Ala VAR_077363

Expression for Myasthenic Syndrome, Congenital, 2a, Slow-Channel

Search GEO for disease gene expression data for Myasthenic Syndrome, Congenital, 2a, Slow-Channel.

Pathways for Myasthenic Syndrome, Congenital, 2a, Slow-Channel

GO Terms for Myasthenic Syndrome, Congenital, 2a, Slow-Channel

Sources for Myasthenic Syndrome, Congenital, 2a, Slow-Channel

3 CDC
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11 DGIdb
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32 ICD10
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45 MESH via Orphanet
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56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
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68 SNOMED-CT via HPO
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71 UMLS via Orphanet
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