CMS1B
MCID: MYS047
MIFTS: 37

Myasthenic Syndrome, Congenital, 1b, Fast-Channel (CMS1B)

Categories: Genetic diseases, Muscle 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 72
Congenital Myasthenic Syndrome 1b, Fast-Channel 12 29 6
Cms1b 57 12 72
Myasthenic Syndrome, Congenital, Fast-Channel 72 70
Myasthenic Syndrome, Congenital, Type 1b, Fast-Channel 39
Myasthenic Syndrome, Fast-Channel Congenital 13
Congenital Myasthenic Syndrome 1b 12
Congenital Myasthenic Syndrome Ib 70
Fccms 72

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
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:

31
myasthenic syndrome, congenital, 1b, fast-channel:
Inheritance autosomal dominant inheritance autosomal recessive inheritance
Onset and clinical course variable expressivity infantile onset


Classifications:



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

UniProtKB/Swiss-Prot : 72 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, 4b, fast-channel and myasthenic syndrome, congenital, 10, 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 CREB Pathway and Nanog in Mammalian ESC Pluripotency. Related phenotypes are scoliosis 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) (Updated 05-Apr-2021)

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

Diseases in the Myasthenic Syndrome, Congenital, 1b, Fast-Channel family:

Myasthenic Syndrome, Congenital, 3b, Fast-Channel Myasthenic Syndrome, Congenital, 4b, Fast-Channel

Diseases related to Myasthenic Syndrome, Congenital, 1b, Fast-Channel via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 23)
# Related Disease Score Top Affiliating Genes
1 myasthenic syndrome, congenital, 4b, fast-channel 31.2 CHRNE C17orf107
2 myasthenic syndrome, congenital, 10 11.2
3 myasthenic syndrome, congenital, 3b, fast-channel 10.9
4 cerebral cavernous malformation, familial 10.9
5 myasthenic syndrome, congenital, 4a, slow-channel 9.9 CHRNE C17orf107
6 congenital myasthenic syndrome associated with acetylcholine receptor deficiency 9.8 CHRNE C17orf107
7 myasthenic syndrome, congenital, 4c, associated with acetylcholine receptor deficiency 9.8 CHRNE C17orf107
8 myasthenia gravis 9.8 CHRNE CHRNA1
9 cystic lymphangioma 9.8 CHRND CHRNA1
10 myasthenic syndrome, congenital, 1a, slow-channel 9.8 CHRND CHRNA1
11 multiple pterygium syndrome, lethal type 9.7 CHRND CHRNA1
12 paramyotonia congenita of von eulenburg 9.7 CHRNE CHRND
13 oligohydramnios 9.7 CHRND CHRNA1
14 tobacco addiction 9.6 CHRND CHRNA1
15 postsynaptic congenital myasthenic syndromes 9.5 CHRNE CHRND CHRNA1
16 myasthenic syndrome, congenital, 13 9.5 CHRNE CHRND CHRNA1
17 neuromuscular junction disease 9.5 CHRNE CHRND CHRNA1
18 multiple pterygium syndrome, escobar variant 9.5 CHRNE CHRND CHRNA1
19 ptosis 9.5 CHRNE CHRND CHRNA1
20 fetal akinesia deformation sequence 1 9.5 CHRND CHRNA1
21 neuromuscular disease 9.5 CHRNE CHRND CHRNA1
22 slow-channel congenital myasthenic syndrome 9.2 CHRNE CHRND CHRNA1 C17orf107
23 congenital myasthenic syndrome 9.2 CHRNE CHRND CHRNA1 C17orf107

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

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

31 (show all 22)
# Description HPO Frequency HPO Source Accession
1 scoliosis 31 HP:0002650
2 ptosis 31 HP:0000508
3 dysarthria 31 HP:0001260
4 dysphagia 31 HP:0002015
5 facial palsy 31 HP:0010628
6 high palate 31 HP:0000218
7 macrotia 31 HP:0000400
8 neonatal hypotonia 31 HP:0001319
9 micrognathia 31 HP:0000347
10 respiratory insufficiency due to muscle weakness 31 HP:0002747
11 motor delay 31 HP:0001270
12 easy fatigability 31 HP:0003388
13 ophthalmoparesis 31 HP:0000597
14 arthrogryposis multiplex congenita 31 HP:0002804
15 weak cry 31 HP:0001612
16 generalized muscle weakness 31 HP:0003324
17 poor suck 31 HP:0002033
18 bulbar palsy 31 HP:0001283
19 neck muscle weakness 31 HP:0000467
20 gowers sign 31 HP:0003391
21 type 2 muscle fiber atrophy 31 HP:0003554
22 decreased miniature endplate potentials 31 HP:0003402

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
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
easy fatigability
generalized muscle weakness
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 (Updated 05-Apr-2021)

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

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

(show all 16)
# Title Authors PMID Year
1
hnRNP H enhances skipping of a nonfunctional exon P3A in CHRNA1 and a mutation disrupting its binding causes congenital myasthenic syndrome. 6 57
18806275 2008
2
Mutation in the AChR ion channel gate underlies a fast channel congenital myasthenic syndrome. 6 57
15079006 2004
3
Mutation causing severe myasthenia reveals functional asymmetry of AChR signature cystine loops in agonist binding and gating. 6 57
12588888 2003
4
Acetylcholine receptor M3 domain: stereochemical and volume contributions to channel gating. 57 6
10195214 1999
5
Congenital myasthenia: end-plate acetylcholine receptors and electrophysiology in five cases. 6 57
7254233 1981
6
Mechanistic diversity underlying fast channel congenital myasthenic syndromes. 61 57
14592870 2003
7
Congenital myasthenic syndromes: pathogenesis, diagnosis, and treatment. 57
25792100 2015
8
Propranolol for familial cerebral cavernous malformation (Treat_CCM): study protocol for a randomized controlled pilot trial. 61
32398113 2020
9
A Novel CCM2 Missense Variant Caused Cerebral Cavernous Malformations in a Chinese Family. 61
33469417 2020
10
Identification of a Novel CCM1 Frameshift Mutation in a Chinese Han Family With Multiple Cerebral Cavernous Malformations. 61
33071727 2020
11
Hereditary Multiple Cerebral Cavernous Malformations Associated with Wilson Disease and Multiple Lipomatosis. 61
28602929 2017
12
Familial Cerebral Cavernous Malformations Are Associated with Adrenal Calcifications on CT Scans: An Imaging Biomarker for a Hereditary Cerebrovascular Condition. 61
28318403 2017
13
Exome capture sequencing identifies a novel CCM1 mutation in a Chinese family with multiple cerebral cavernous malformations. 61
26643368 2016
14
A Novel CCM2 Gene Mutation Associated with Familial Cerebral Cavernous Malformation. 61
27708576 2016
15
Angioleiomyomas of the dura: rare entities that lack KRIT1 mutations. 61
22261708 2012
16
Congenital Myasthenic Syndromes 61
20301347 2003

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

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

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 CHRNA1 NM_001039523.3(CHRNA1):c.988G>A (p.Val330Ile) SNV Pathogenic 18382 rs137852804 GRCh37: 2:175614763-175614763
GRCh38: 2:174750035-174750035
2 CHRNA1 NM_001039523.3(CHRNA1):c.832T>G (p.Phe278Val) SNV Pathogenic 18383 rs137852805 GRCh37: 2:175618252-175618252
GRCh38: 2:174753524-174753524
3 CHRNA1 NM_001039523.3(CHRNA1):c.901T>C (p.Phe301Leu) SNV Pathogenic 18384 rs137852806 GRCh37: 2:175614850-175614850
GRCh38: 2:174750122-174750122
4 CHRNA1 NM_001039523.3(CHRNA1):c.529G>C (p.Val177Leu) SNV Pathogenic 18385 rs137852807 GRCh37: 2:175619033-175619033
GRCh38: 2:174754305-174754305
5 CHRNA1 CHRNA1, 1-BP DEL, 381C Deletion Pathogenic 18386 GRCh37:
GRCh38:
6 CHRNA1 CHRNA1, IVS3AS, G-A, -8 SNV Pathogenic 29581 GRCh37:
GRCh38:
7 CHRND NM_000751.3(CHRND):c.1319A>G (p.Asp440Gly) SNV Pathogenic 242638 rs373747090 GRCh37: 2:233399000-233399000
GRCh38: 2:232534290-232534290
8 CHRNA1 NM_001039523.3(CHRNA1):c.1072C>T (p.Arg358Trp) SNV Pathogenic 29582 rs374391312 GRCh37: 2:175614679-175614679
GRCh38: 2:174749951-174749951
9 CHRNE , C17orf107 NM_000080.4(CHRNE):c.421C>A (p.Pro141Thr) SNV Pathogenic 135656 rs483353045 GRCh37: 17:4805306-4805306
GRCh38: 17:4902011-4902011

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

72
# 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

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
12.58 CHRNE CHRND CHRNA1
2
Show member pathways
12.48 CHRNE CHRND CHRNA1
3
Show member pathways
12.18 CHRNE CHRND CHRNA1
4
Show member pathways
11.04 CHRNE CHRND CHRNA1
5 9.88 CHRNE CHRND CHRNA1

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 integral component of plasma membrane GO:0005887 9.61 CHRNE CHRND CHRNA1
2 cell junction GO:0030054 9.58 CHRNE CHRND CHRNA1
3 synapse GO:0045202 9.54 CHRNE CHRND CHRNA1
4 neuron projection GO:0043005 9.5 CHRNE CHRND CHRNA1
5 postsynaptic membrane GO:0045211 9.33 CHRNE CHRND CHRNA1
6 integral component of postsynaptic specialization membrane GO:0099060 9.26 CHRND CHRNA1
7 neuromuscular junction GO:0031594 9.13 CHRNE CHRND CHRNA1
8 acetylcholine-gated channel complex GO:0005892 8.8 CHRNE CHRND CHRNA1

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

(show all 14)
# Name GO ID Score Top Affiliating Genes
1 ion transport GO:0006811 9.7 CHRNE CHRND CHRNA1
2 ion transmembrane transport GO:0034220 9.65 CHRNE CHRND CHRNA1
3 chemical synaptic transmission GO:0007268 9.58 CHRNE CHRND CHRNA1
4 muscle contraction GO:0006936 9.54 CHRNE CHRND
5 cation transport GO:0006812 9.51 CHRND CHRNA1
6 regulation of membrane potential GO:0042391 9.5 CHRNE CHRND CHRNA1
7 skeletal muscle contraction GO:0003009 9.49 CHRND CHRNA1
8 neuromuscular process GO:0050905 9.46 CHRND CHRNA1
9 synaptic transmission, cholinergic GO:0007271 9.43 CHRNE CHRNA1
10 musculoskeletal movement GO:0050881 9.37 CHRND CHRNA1
11 excitatory postsynaptic potential GO:0060079 9.33 CHRNE CHRND CHRNA1
12 skeletal muscle tissue growth GO:0048630 9.26 CHRND CHRNA1
13 nervous system process GO:0050877 9.13 CHRNE CHRND CHRNA1
14 regulation of postsynaptic membrane potential GO:0060078 8.8 CHRNE CHRND CHRNA1

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

# Name GO ID Score Top Affiliating Genes
1 transmembrane signaling receptor activity GO:0004888 9.61 CHRNE CHRND CHRNA1
2 ion channel activity GO:0005216 9.54 CHRNE CHRND CHRNA1
3 neurotransmitter receptor activity GO:0030594 9.43 CHRNE CHRND CHRNA1
4 acetylcholine receptor activity GO:0015464 9.4 CHRNE CHRNA1
5 extracellular ligand-gated ion channel activity GO:0005230 9.33 CHRNE CHRND CHRNA1
6 acetylcholine binding GO:0042166 9.32 CHRND CHRNA1
7 transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential GO:1904315 9.13 CHRNE CHRND CHRNA1
8 acetylcholine-gated cation-selective channel activity GO:0022848 8.8 CHRNE CHRND CHRNA1

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

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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