MCID: MYS062
MIFTS: 24

Myasthenic Syndrome, Congenital, 2a, Slow-Channel

Categories: Genetic 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 75 29 6
Cms2a 57 75
Myasthenic Syndrome, Congenital, Postsynaptic Slow-Channel 73

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant

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


HPO:

32
myasthenic syndrome, congenital, 2a, slow-channel:
Onset and clinical course congenital onset
Inheritance autosomal dominant inheritance


Classifications:



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

UniProtKB/Swiss-Prot : 75 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), and among its related pathways/superpathways is Nanog in Mammalian ESC Pluripotency. Affiliated tissues include skeletal muscle, and related phenotypes are high palate and narrow face

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)

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 10.9
3 congenital myasthenic syndrome 9.0 CHRNB1 FGF11

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

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
ptosis
ophthalmoplegia

Muscle Soft Tissue:
easy fatigability
muscle atrophy
hypotonia, neonatal
endplate myopathy
decremental response to repetitive nerve stimulation
more
Skeletal:
joint contractures (in some patients)

Growth Other:
small body habitus

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

Head And Neck Mouth:
high-arched palate

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


Clinical features from OMIM:

616313

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

32 (show all 10)
# Description HPO Frequency HPO Source Accession
1 high palate 32 HP:0000218
2 narrow face 32 HP:0000275
3 long face 32 HP:0000276
4 ptosis 32 HP:0000508
5 ophthalmoplegia 32 HP:0000602
6 neonatal hypotonia 32 HP:0001319
7 flexion contracture 32 occasional (7.5%) HP:0001371
8 skeletal muscle atrophy 32 HP:0003202
9 easy fatigability 32 HP:0003388
10 facial palsy 32 HP:0010628

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:

41
Skeletal Muscle

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

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

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

75
# 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

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

6
(show all 48)
# Gene Variation Type Significance SNP ID Assembly Location
1 CHRNB1 NM_000747.2(CHRNB1): c.865G> A (p.Val289Met) single nucleotide variant Pathogenic/Likely pathogenic rs137852810 GRCh37 Chromosome 17, 7357660: 7357660
2 CHRNB1 NM_000747.2(CHRNB1): c.865G> A (p.Val289Met) single nucleotide variant Pathogenic/Likely pathogenic rs137852810 GRCh38 Chromosome 17, 7454341: 7454341
3 CHRNB1 NM_000747.2(CHRNB1): c.853C> A (p.Leu285Met) single nucleotide variant Pathogenic rs137852811 GRCh37 Chromosome 17, 7357648: 7357648
4 CHRNB1 NM_000747.2(CHRNB1): c.853C> A (p.Leu285Met) single nucleotide variant Pathogenic rs137852811 GRCh38 Chromosome 17, 7454329: 7454329
5 CHRNB1 NM_000747.2(CHRNB1): c.342G> A (p.Val114=) single nucleotide variant Conflicting interpretations of pathogenicity rs75019736 GRCh37 Chromosome 17, 7350250: 7350250
6 CHRNB1 NM_000747.2(CHRNB1): c.342G> A (p.Val114=) single nucleotide variant Conflicting interpretations of pathogenicity rs75019736 GRCh38 Chromosome 17, 7446931: 7446931
7 CHRNB1 NM_000747.2(CHRNB1): c.1045-6C> G single nucleotide variant Benign/Likely benign rs79209506 GRCh37 Chromosome 17, 7358597: 7358597
8 CHRNB1 NM_000747.2(CHRNB1): c.1045-6C> G single nucleotide variant Benign/Likely benign rs79209506 GRCh38 Chromosome 17, 7455278: 7455278
9 CHRNB1 NM_000747.2(CHRNB1): c.84T> C (p.Gly28=) single nucleotide variant Benign rs138041351 GRCh37 Chromosome 17, 7348614: 7348614
10 CHRNB1 NM_000747.2(CHRNB1): c.84T> C (p.Gly28=) single nucleotide variant Benign rs138041351 GRCh38 Chromosome 17, 7445295: 7445295
11 CHRNB1 NM_000747.2(CHRNB1): c.903C> T (p.Thr301=) single nucleotide variant Conflicting interpretations of pathogenicity rs117168441 GRCh37 Chromosome 17, 7357698: 7357698
12 CHRNB1 NM_000747.2(CHRNB1): c.903C> T (p.Thr301=) single nucleotide variant Conflicting interpretations of pathogenicity rs117168441 GRCh38 Chromosome 17, 7454379: 7454379
13 CHRNB1 NM_000747.2(CHRNB1): c.1044+9G> A single nucleotide variant Conflicting interpretations of pathogenicity rs143871421 GRCh37 Chromosome 17, 7357848: 7357848
14 CHRNB1 NM_000747.2(CHRNB1): c.1044+9G> A single nucleotide variant Conflicting interpretations of pathogenicity rs143871421 GRCh38 Chromosome 17, 7454529: 7454529
15 CHRNB1 NM_000747.2(CHRNB1): c.727C> T (p.Arg243Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs199875082 GRCh37 Chromosome 17, 7352014: 7352014
16 CHRNB1 NM_000747.2(CHRNB1): c.727C> T (p.Arg243Cys) single nucleotide variant Conflicting interpretations of pathogenicity rs199875082 GRCh38 Chromosome 17, 7448695: 7448695
17 CHRNB1 NM_000747.2(CHRNB1): c.198+3G> T single nucleotide variant Uncertain significance GRCh38 Chromosome 17, 7445412: 7445412
18 CHRNB1 NM_000747.2(CHRNB1): c.198+3G> T single nucleotide variant Uncertain significance GRCh37 Chromosome 17, 7348731: 7348731
19 CHRNB1 NM_000747.2(CHRNB1): c.611-9C> T single nucleotide variant Benign rs538827412 GRCh38 Chromosome 17, 7448570: 7448570
20 CHRNB1 NM_000747.2(CHRNB1): c.611-9C> T single nucleotide variant Benign rs538827412 GRCh37 Chromosome 17, 7351889: 7351889
21 CHRNB1 NM_000747.2(CHRNB1): c.647G> A (p.Arg216Gln) single nucleotide variant Uncertain significance rs200684767 GRCh37 Chromosome 17, 7351934: 7351934
22 CHRNB1 NM_000747.2(CHRNB1): c.647G> A (p.Arg216Gln) single nucleotide variant Uncertain significance rs200684767 GRCh38 Chromosome 17, 7448615: 7448615
23 CHRNB1 NM_000747.2(CHRNB1): c.1003C> T (p.Arg335Cys) single nucleotide variant Uncertain significance rs779467380 GRCh38 Chromosome 17, 7454479: 7454479
24 CHRNB1 NM_000747.2(CHRNB1): c.1003C> T (p.Arg335Cys) single nucleotide variant Uncertain significance rs779467380 GRCh37 Chromosome 17, 7357798: 7357798
25 CHRNB1 NM_000747.2(CHRNB1): c.1359C> T (p.His453=) single nucleotide variant Benign rs142053338 GRCh37 Chromosome 17, 7359254: 7359254
26 CHRNB1 NM_000747.2(CHRNB1): c.1359C> T (p.His453=) single nucleotide variant Benign rs142053338 GRCh38 Chromosome 17, 7455935: 7455935
27 CHRNB1 NM_000747.2(CHRNB1): c.516C> G (p.Tyr172Ter) single nucleotide variant Pathogenic rs201033437 GRCh38 Chromosome 17, 7447556: 7447556
28 CHRNB1 NM_000747.2(CHRNB1): c.516C> G (p.Tyr172Ter) single nucleotide variant Pathogenic rs201033437 GRCh37 Chromosome 17, 7350875: 7350875
29 CHRNB1 NM_000747.2(CHRNB1): c.728G> A (p.Arg243His) single nucleotide variant Uncertain significance rs200409941 GRCh38 Chromosome 17, 7448696: 7448696
30 CHRNB1 NM_000747.2(CHRNB1): c.728G> A (p.Arg243His) single nucleotide variant Uncertain significance rs200409941 GRCh37 Chromosome 17, 7352015: 7352015
31 CHRNB1 NM_000747.2(CHRNB1): c.1218-9_1218-7delCTC deletion Conflicting interpretations of pathogenicity GRCh38 Chromosome 17, 7455785: 7455787
32 CHRNB1 NM_000747.2(CHRNB1): c.1218-9_1218-7delCTC deletion Conflicting interpretations of pathogenicity GRCh37 Chromosome 17, 7359104: 7359106
33 CHRNB1 NM_000747.2(CHRNB1): c.36_37delGCinsAA (p.Leu13Met) indel Uncertain significance GRCh37 Chromosome 17, 7348482: 7348483
34 CHRNB1 NM_000747.2(CHRNB1): c.36_37delGCinsAA (p.Leu13Met) indel Uncertain significance GRCh38 Chromosome 17, 7445163: 7445164
35 CHRNB1 NM_000747.2(CHRNB1): c.257A> G (p.Tyr86Cys) single nucleotide variant Uncertain significance GRCh37 Chromosome 17, 7350165: 7350165
36 CHRNB1 NM_000747.2(CHRNB1): c.257A> G (p.Tyr86Cys) single nucleotide variant Uncertain significance GRCh38 Chromosome 17, 7446846: 7446846
37 CHRNB1 NM_000747.2(CHRNB1): c.593A> G (p.His198Arg) single nucleotide variant Uncertain significance rs76251791 GRCh38 Chromosome 17, 7447633: 7447633
38 CHRNB1 NM_000747.2(CHRNB1): c.593A> G (p.His198Arg) single nucleotide variant Uncertain significance rs76251791 GRCh37 Chromosome 17, 7350952: 7350952
39 CHRNB1 NM_000747.2(CHRNB1): c.877C> T (p.Leu293=) single nucleotide variant Likely benign rs956543933 GRCh38 Chromosome 17, 7454353: 7454353
40 CHRNB1 NM_000747.2(CHRNB1): c.877C> T (p.Leu293=) single nucleotide variant Likely benign rs956543933 GRCh37 Chromosome 17, 7357672: 7357672
41 CHRNB1 NM_000747.2(CHRNB1): c.300G> A (p.Ser100=) single nucleotide variant Likely benign rs376099204 GRCh37 Chromosome 17, 7350208: 7350208
42 CHRNB1 NM_000747.2(CHRNB1): c.300G> A (p.Ser100=) single nucleotide variant Likely benign rs376099204 GRCh38 Chromosome 17, 7446889: 7446889
43 CHRNB1 NM_000747.2(CHRNB1): c.1126T> C (p.Cys376Arg) single nucleotide variant Uncertain significance rs150290595 GRCh38 Chromosome 17, 7455365: 7455365
44 CHRNB1 NM_000747.2(CHRNB1): c.1126T> C (p.Cys376Arg) single nucleotide variant Uncertain significance rs150290595 GRCh37 Chromosome 17, 7358684: 7358684
45 CHRNB1 NM_000747.2(CHRNB1): c.1248G> A (p.Leu416=) single nucleotide variant Likely benign rs774757392 GRCh38 Chromosome 17, 7455824: 7455824
46 CHRNB1 NM_000747.2(CHRNB1): c.1248G> A (p.Leu416=) single nucleotide variant Likely benign rs774757392 GRCh37 Chromosome 17, 7359143: 7359143
47 CHRNB1 NM_000747.2(CHRNB1): c.564C> T (p.Asp188=) single nucleotide variant Likely benign rs77592498 GRCh38 Chromosome 17, 7447604: 7447604
48 CHRNB1 NM_000747.2(CHRNB1): c.564C> T (p.Asp188=) single nucleotide variant Likely benign rs77592498 GRCh37 Chromosome 17, 7350923: 7350923

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

Pathways related to Myasthenic Syndrome, Congenital, 2a, Slow-Channel according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.67 CHRNB1 FGF11

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

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

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