MCID: MYS047
MIFTS: 33

Myasthenic Syndrome, Congenital, 1b, Fast-Channel

Categories: Genetic diseases, Neuronal diseases

Aliases & Classifications for Myasthenic Syndrome, Congenital, 1b, Fast-Channel

MalaCards integrated aliases for Myasthenic Syndrome, Congenital, 1b, Fast-Channel:

Name: Myasthenic Syndrome, Congenital, 1b, Fast-Channel 57 75
Congenital Myasthenic Syndrome 1b, Fast-Channel 12 29 6
Cms1b 57 12 75
Myasthenic Syndrome, Congenital, Fast-Channel 75 73
Myasthenic Syndrome, Congenital, Type 1b, Fast-Channel 40
Myasthenic Syndrome, Fast-Channel Congenital 13
Congenital Myasthenic Syndrome 1b 12
Congenital Myasthenic Syndrome Ib 73
Fccms 75

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive
autosomal dominant

Miscellaneous:
variable severity
onset in infancy or early childhood
favorable response to acetylcholinesterase inhibitors
favorable response to 3,4-diaminopyridine
rare autosomal dominant inheritance has been reported


HPO:

32
myasthenic syndrome, congenital, 1b, fast-channel:
Onset and clinical course variable expressivity infantile onset
Inheritance autosomal recessive inheritance autosomal dominant inheritance


Classifications:



Summaries for Myasthenic Syndrome, Congenital, 1b, Fast-Channel

UniProtKB/Swiss-Prot : 75 Myasthenic syndrome, congenital, 1B, fast-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. CMS1B is a fast-channel myasthenic syndrome. It is caused by kinetic abnormalities of the AChR, resulting in brief opening and activity of the channel, with a rapid decay in endplate current, failure to achieve threshold depolarization of the endplate and consequent failure to fire an action potential.

MalaCards based summary : Myasthenic Syndrome, Congenital, 1b, Fast-Channel, also known as congenital myasthenic syndrome 1b, fast-channel, is related to myasthenic syndrome, congenital, 10 and myasthenic syndrome, congenital, 3b, fast-channel, and has symptoms including facial paresis An important gene associated with Myasthenic Syndrome, Congenital, 1b, Fast-Channel is CHRNA1 (Cholinergic Receptor Nicotinic Alpha 1 Subunit), and among its related pathways/superpathways are Transmission across Chemical Synapses and Regulation of lipid metabolism Insulin signaling-generic cascades. Related phenotypes are high palate and ptosis

Disease Ontology : 12 A congenital myasthenic syndrome characterized by defects in postsynaptic neuromuscular junctions with early-onset progressive muscle weakness that has material basis in mutation in the CHRNA1 gene on chromosome 2q.

OMIM : 57 Fast-channel congenital myasthenic syndrome (FCCMS) 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 (AChR) channel, specifically from abnormally brief opening and activity of the channel, with a rapid decay in endplate current and a failure to reach the threshold for depolarization. Treatment with pyridostigmine or amifampridine may be helpful; quinine, quinidine, and fluoxetine should be avoided (summary by Sine et al., 2003 and Engel et al., 2015). For a discussion of genetic heterogeneity of CMS, see CMS1A (601462). (608930)

Related Diseases for Myasthenic Syndrome, Congenital, 1b, Fast-Channel

Graphical network of the top 20 diseases related to Myasthenic Syndrome, Congenital, 1b, Fast-Channel:



Diseases related to Myasthenic Syndrome, Congenital, 1b, Fast-Channel

Symptoms & Phenotypes for Myasthenic Syndrome, Congenital, 1b, Fast-Channel

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
ptosis
ophthalmoparesis

Abdomen Gastrointestinal:
dysphagia
poor suck
poor feeding due to muscle weakness

Head And Neck Neck:
neck muscle weakness

Respiratory:
respiratory insufficiency due to muscle weakness (especially in infancy)

Muscle Soft Tissue:
dysarthria
generalized muscle weakness
easy fatigability
gowers sign
hypotonia, neonatal
more
Voice:
weak cry

Head And Neck Face:
facial muscle weakness

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


Clinical features from OMIM:

608930

Human phenotypes related to Myasthenic Syndrome, Congenital, 1b, Fast-Channel:

32 (show all 22)
# Description HPO Frequency HPO Source Accession
1 high palate 32 HP:0000218
2 ptosis 32 HP:0000508
3 dysarthria 32 HP:0001260
4 dysphagia 32 HP:0002015
5 scoliosis 32 HP:0002650
6 facial palsy 32 HP:0010628
7 macrotia 32 HP:0000400
8 neonatal hypotonia 32 HP:0001319
9 respiratory insufficiency due to muscle weakness 32 HP:0002747
10 generalized muscle weakness 32 HP:0003324
11 micrognathia 32 HP:0000347
12 ophthalmoparesis 32 HP:0000597
13 arthrogryposis multiplex congenita 32 HP:0002804
14 motor delay 32 HP:0001270
15 weak cry 32 HP:0001612
16 neck muscle weakness 32 HP:0000467
17 poor suck 32 HP:0002033
18 bulbar palsy 32 HP:0001283
19 type 2 muscle fiber atrophy 32 HP:0003554
20 easy fatigability 32 HP:0003388
21 gowers sign 32 HP:0003391
22 decreased miniature endplate potentials 32 HP:0003402

UMLS symptoms related to Myasthenic Syndrome, Congenital, 1b, Fast-Channel:


facial paresis

Drugs & Therapeutics for Myasthenic Syndrome, Congenital, 1b, Fast-Channel

Search Clinical Trials , NIH Clinical Center for Myasthenic Syndrome, Congenital, 1b, Fast-Channel

Genetic Tests for Myasthenic Syndrome, Congenital, 1b, Fast-Channel

Genetic tests related to Myasthenic Syndrome, Congenital, 1b, Fast-Channel:

# Genetic test Affiliating Genes
1 Congenital Myasthenic Syndrome 1b, Fast-Channel 29 CHRNA1

Anatomical Context for Myasthenic Syndrome, Congenital, 1b, Fast-Channel

Publications for Myasthenic Syndrome, Congenital, 1b, Fast-Channel

Variations for Myasthenic Syndrome, Congenital, 1b, Fast-Channel

UniProtKB/Swiss-Prot genetic disease variations for Myasthenic Syndrome, Congenital, 1b, Fast-Channel:

75
# Symbol AA change Variation ID SNP ID
1 CHRNA1 p.Phe278Val VAR_021206 rs137852805
2 CHRNA1 p.Phe301Leu VAR_021208 rs137852806
3 CHRNA1 p.Val330Ile VAR_021209 rs137852804
4 CHRNA1 p.Val177Leu VAR_038599 rs137852807

ClinVar genetic disease variations for Myasthenic Syndrome, Congenital, 1b, Fast-Channel:

6
(show all 19)
# Gene Variation Type Significance SNP ID Assembly Location
1 CHRNA1 NM_001039523.2(CHRNA1): c.988G> A (p.Val330Ile) single nucleotide variant Pathogenic rs137852804 GRCh37 Chromosome 2, 175614763: 175614763
2 CHRNA1 NM_001039523.2(CHRNA1): c.988G> A (p.Val330Ile) single nucleotide variant Pathogenic rs137852804 GRCh38 Chromosome 2, 174750035: 174750035
3 CHRNA1 NM_001039523.2(CHRNA1): c.832T> G (p.Phe278Val) single nucleotide variant Pathogenic rs137852805 GRCh37 Chromosome 2, 175618252: 175618252
4 CHRNA1 NM_001039523.2(CHRNA1): c.832T> G (p.Phe278Val) single nucleotide variant Pathogenic rs137852805 GRCh38 Chromosome 2, 174753524: 174753524
5 CHRNA1 NM_001039523.2(CHRNA1): c.901T> C (p.Phe301Leu) single nucleotide variant Pathogenic rs137852806 GRCh37 Chromosome 2, 175614850: 175614850
6 CHRNA1 NM_001039523.2(CHRNA1): c.901T> C (p.Phe301Leu) single nucleotide variant Pathogenic rs137852806 GRCh38 Chromosome 2, 174750122: 174750122
7 CHRNA1 NM_001039523.2(CHRNA1): c.529G> C (p.Val177Leu) single nucleotide variant Pathogenic rs137852807 GRCh37 Chromosome 2, 175619033: 175619033
8 CHRNA1 NM_001039523.2(CHRNA1): c.529G> C (p.Val177Leu) single nucleotide variant Pathogenic rs137852807 GRCh38 Chromosome 2, 174754305: 174754305
9 CHRNA1 CHRNA1, 1-BP DEL, 381C deletion Pathogenic
10 CHRNA1 CHRNA1, IVS3AS, G-A, -8 single nucleotide variant Pathogenic
11 CHRNA1 CHRNA1, ARG313TRP undetermined variant Pathogenic
12 CHRNE NM_000080.3(CHRNE): c.421C> A (p.Pro141Thr) single nucleotide variant Pathogenic rs483353045 GRCh37 Chromosome 17, 4805306: 4805306
13 CHRNE NM_000080.3(CHRNE): c.421C> A (p.Pro141Thr) single nucleotide variant Pathogenic rs483353045 GRCh38 Chromosome 17, 4902011: 4902011
14 CHRND NM_000751.2(CHRND): c.73G> T (p.Glu25Ter) single nucleotide variant no interpretation for the single variant rs797044480 GRCh37 Chromosome 2, 233391259: 233391259
15 CHRND NM_000751.2(CHRND): c.73G> T (p.Glu25Ter) single nucleotide variant no interpretation for the single variant rs797044480 GRCh38 Chromosome 2, 232526549: 232526549
16 CHRND NM_000751.2(CHRND): c.1319A> G (p.Asp440Gly) single nucleotide variant no interpretation for the single variant rs373747090 GRCh37 Chromosome 2, 233399000: 233399000
17 CHRND NM_000751.2(CHRND): c.1319A> G (p.Asp440Gly) single nucleotide variant no interpretation for the single variant rs373747090 GRCh38 Chromosome 2, 232534290: 232534290
18 CHRNA1 NM_000079.3(CHRNA1): c.1139T> C (p.Met380Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs149292107 GRCh37 Chromosome 2, 175613411: 175613411
19 CHRNA1 NM_000079.3(CHRNA1): c.1139T> C (p.Met380Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs149292107 GRCh38 Chromosome 2, 174748683: 174748683

Expression for Myasthenic Syndrome, Congenital, 1b, Fast-Channel

Search GEO for disease gene expression data for Myasthenic Syndrome, Congenital, 1b, Fast-Channel.

Pathways for Myasthenic Syndrome, Congenital, 1b, Fast-Channel

Pathways related to Myasthenic Syndrome, Congenital, 1b, Fast-Channel according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.11 CHRNA1 CHRNE
2
Show member pathways
11.93 CHRNA1 CHRNE
3
Show member pathways
10.89 CHRNA1 CHRNE
4 9.7 CHRNA1 CHRNE

GO Terms for Myasthenic Syndrome, Congenital, 1b, Fast-Channel

Cellular components related to Myasthenic Syndrome, Congenital, 1b, Fast-Channel according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cell junction GO:0030054 9.32 CHRNA1 CHRNE
2 synapse GO:0045202 9.26 CHRNA1 CHRNE
3 neuron projection GO:0043005 9.16 CHRNA1 CHRNE
4 postsynaptic membrane GO:0045211 8.96 CHRNA1 CHRNE
5 acetylcholine-gated channel complex GO:0005892 8.62 CHRNA1 CHRNE

Biological processes related to Myasthenic Syndrome, Congenital, 1b, Fast-Channel according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ion transport GO:0006811 9.48 CHRNA1 CHRNE
2 ion transmembrane transport GO:0034220 9.46 CHRNA1 CHRNE
3 chemical synaptic transmission GO:0007268 9.43 CHRNA1 CHRNE
4 regulation of membrane potential GO:0042391 9.4 CHRNA1 CHRNE
5 excitatory postsynaptic potential GO:0060079 9.37 CHRNA1 CHRNE
6 nervous system process GO:0050877 9.32 CHRNA1 CHRNE
7 response to nicotine GO:0035094 9.26 CHRNA1 CHRNE
8 neuromuscular synaptic transmission GO:0007274 9.16 CHRNA1 CHRNE
9 regulation of postsynaptic membrane potential GO:0060078 8.96 CHRNA1 CHRNE
10 synaptic transmission, cholinergic GO:0007271 8.62 CHRNA1 CHRNE

Molecular functions related to Myasthenic Syndrome, Congenital, 1b, Fast-Channel according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ion channel activity GO:0005216 9.37 CHRNA1 CHRNE
2 extracellular ligand-gated ion channel activity GO:0005230 9.32 CHRNA1 CHRNE
3 ligand-gated ion channel activity GO:0015276 9.26 CHRNA1 CHRNE
4 acetylcholine binding GO:0042166 9.16 CHRNA1 CHRNE
5 acetylcholine-gated cation-selective channel activity GO:0022848 8.96 CHRNA1 CHRNE
6 acetylcholine receptor activity GO:0015464 8.62 CHRNA1 CHRNE

Sources for Myasthenic Syndrome, Congenital, 1b, Fast-Channel

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
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