CMS4B
MCID: MYS060
MIFTS: 26

Myasthenic Syndrome, Congenital, 4b, Fast-Channel (CMS4B)

Categories: Genetic diseases, Muscle diseases, Neuronal diseases

Aliases & Classifications for Myasthenic Syndrome, Congenital, 4b, Fast-Channel

MalaCards integrated aliases for Myasthenic Syndrome, Congenital, 4b, Fast-Channel:

Name: Myasthenic Syndrome, Congenital, 4b, Fast-Channel 57 72 29 6
Cms4b 57 12 72
Myasthenic Syndrome, Congenital, Type 4b, Fast-Channel 39
Congenital Myasthenic Syndrome 4b Fast-Channel 12
Congenital Myasthenic Syndrome 4b 12

Characteristics:

OMIM®:

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

Miscellaneous:
onset in infancy
early death may occur
may respond to cholinesterase inhibitors of amifampridine


HPO:

31
myasthenic syndrome, congenital, 4b, fast-channel:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset


Classifications:



External Ids:

Disease Ontology 12 DOID:0110677
OMIM® 57 616324
OMIM Phenotypic Series 57 PS601462
MeSH 44 D020294

Summaries for Myasthenic Syndrome, Congenital, 4b, Fast-Channel

UniProtKB/Swiss-Prot : 72 Myasthenic syndrome, congenital, 4B, 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. CMS4B 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, 4b, Fast-Channel, also known as cms4b, is related to myasthenic syndrome, congenital, 1b, fast-channel and myasthenic syndrome, congenital, 4a, slow-channel. An important gene associated with Myasthenic Syndrome, Congenital, 4b, Fast-Channel is CHRNE (Cholinergic Receptor Nicotinic Epsilon Subunit). Related phenotypes are ptosis and facial palsy

Disease Ontology : 12 A congenital myasthenic syndrome characterized by autosomal recessive inheritance of postsynaptic neuromuscular junction defects, early-onset progressive muscle weakness, and kinetic abnormalities of the AChR channel that has material basis in homozygous or compound heterozygous mutation in the CHRNE gene on chromosome 17p13.

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 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). (616324) (Updated 05-Apr-2021)

Related Diseases for Myasthenic Syndrome, Congenital, 4b, Fast-Channel

Graphical network of the top 20 diseases related to Myasthenic Syndrome, Congenital, 4b, Fast-Channel:



Diseases related to Myasthenic Syndrome, Congenital, 4b, Fast-Channel

Symptoms & Phenotypes for Myasthenic Syndrome, Congenital, 4b, Fast-Channel

Human phenotypes related to Myasthenic Syndrome, Congenital, 4b, Fast-Channel:

31 (show all 8)
# Description HPO Frequency HPO Source Accession
1 ptosis 31 HP:0000508
2 facial palsy 31 HP:0010628
3 respiratory insufficiency 31 HP:0002093
4 neonatal hypotonia 31 HP:0001319
5 easy fatigability 31 HP:0003388
6 ophthalmoplegia 31 HP:0000602
7 feeding difficulties 31 HP:0011968
8 neck muscle weakness 31 HP:0000467

Symptoms via clinical synopsis from OMIM®:

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

Respiratory:
respiratory insufficiency

Head And Neck Face:
facial muscle weakness

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

Muscle Soft Tissue:
muscle weakness
easy fatigability
hypotonia, neonatal
decremental response to repetitive nerve stimulation
decreased amplitudes of the miniature endplate potential (mepp) and current (mepc)
more
Head And Neck Neck:
neck muscle weakness

Abdomen Gastrointestinal:
poor feeding

Clinical features from OMIM®:

616324 (Updated 05-Apr-2021)

Drugs & Therapeutics for Myasthenic Syndrome, Congenital, 4b, Fast-Channel

Search Clinical Trials , NIH Clinical Center for Myasthenic Syndrome, Congenital, 4b, Fast-Channel

Genetic Tests for Myasthenic Syndrome, Congenital, 4b, Fast-Channel

Genetic tests related to Myasthenic Syndrome, Congenital, 4b, Fast-Channel:

# Genetic test Affiliating Genes
1 Myasthenic Syndrome, Congenital, 4b, Fast-Channel 29 CHRNE

Anatomical Context for Myasthenic Syndrome, Congenital, 4b, Fast-Channel

Publications for Myasthenic Syndrome, Congenital, 4b, Fast-Channel

Articles related to Myasthenic Syndrome, Congenital, 4b, Fast-Channel:

# Title Authors PMID Year
1
Highly fatal fast-channel syndrome caused by AChR ε subunit mutation at the agonist binding site. 6 57
22592360 2012
2
Fundamental gating mechanism of nicotinic receptor channel revealed by mutation causing a congenital myasthenic syndrome. 6 57
10962020 2000
3
Congenital myasthenic syndrome caused by decreased agonist binding affinity due to a mutation in the acetylcholine receptor epsilon subunit. 57 6
8755487 1996
4
Congenital myasthenic syndromes: II. Syndrome attributed to abnormal interaction of acetylcholine with its receptor. 6 57
8232384 1993
5
Congenital myasthenic syndromes: pathogenesis, diagnosis, and treatment. 57
25792100 2015
6
Mechanistic diversity underlying fast channel congenital myasthenic syndromes. 57
14592870 2003

Variations for Myasthenic Syndrome, Congenital, 4b, Fast-Channel

ClinVar genetic disease variations for Myasthenic Syndrome, Congenital, 4b, Fast-Channel:

6 (show all 17)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 CHRNE , C17orf107 NM_000080.4(CHRNE):c.422C>T (p.Pro141Leu) SNV Pathogenic 18346 rs121909512 GRCh37: 17:4805305-4805305
GRCh38: 17:4902010-4902010
2 CHRNE NM_000080.4(CHRNE):c.1291G>C (p.Ala431Pro) SNV Pathogenic 18361 rs121909517 GRCh37: 17:4802331-4802331
GRCh38: 17:4899036-4899036
3 CHRNE , C17orf107 NM_000080.4(CHRNE):c.223T>C (p.Trp75Arg) SNV Pathogenic 40201 rs193919341 GRCh37: 17:4805756-4805756
GRCh38: 17:4902461-4902461
4 CHRNE , C17orf107 NM_000080.4(CHRNE):c.488C>T (p.Ser163Leu) SNV Pathogenic 18360 rs121909516 GRCh37: 17:4805239-4805239
GRCh38: 17:4901944-4901944
5 CHRNE , C17orf107 NM_000080.4(CHRNE):c.614_620del (p.Trp205fs) Deletion Pathogenic 18357 rs753828284 GRCh37: 17:4804467-4804473
GRCh38: 17:4901172-4901178
6 CHRNE NM_000080.4(CHRNE):c.1364ACA[1] (p.Asn456del) Microsatellite Pathogenic 973529 GRCh37: 17:4802144-4802146
GRCh38: 17:4898849-4898851
7 CHRNE NM_000080.4(CHRNE):c.1327del Deletion Pathogenic 243031 rs763258280 GRCh37: 17:4802186-4802186
GRCh38: 17:4898891-4898891
8 CHRNE , C17orf107 NM_000080.4(CHRNE):c.103T>C (p.Tyr35His) SNV Pathogenic 282036 rs144169073 GRCh37: 17:4806002-4806002
GRCh38: 17:4902707-4902707
9 CHRNE NM_000080.4(CHRNE):c.992G>A (p.Arg331Gln) SNV Pathogenic 641946 rs760022829 GRCh37: 17:4802803-4802803
GRCh38: 17:4899508-4899508
10 CHRNE NM_000080.3(CHRNE):c.-95G>A SNV Likely pathogenic 465866 rs990457690 GRCh37: 17:4806453-4806453
GRCh38: 17:4903158-4903158
11 CHRNE NM_000080.4(CHRNE):c.3G>A (p.Met1Ile) SNV Likely pathogenic 931856 GRCh37: 17:4806356-4806356
GRCh38: 17:4903061-4903061
12 CHRNE NM_000080.4(CHRNE):c.37G>A (p.Gly13Arg) SNV Likely pathogenic 18359 rs372635387 GRCh37: 17:4806322-4806322
GRCh38: 17:4903027-4903027
13 CHRNE , C17orf107 NM_000080.4(CHRNE):c.917+271C>G SNV Uncertain significance 930868 GRCh37: 17:4803817-4803817
GRCh38: 17:4900522-4900522
14 CHRNE , C17orf107 NM_000080.4(CHRNE):c.439G>A (p.Val147Ile) SNV Uncertain significance 931855 GRCh37: 17:4805288-4805288
GRCh38: 17:4901993-4901993
15 CHRNE , C17orf107 NM_000080.4(CHRNE):c.506A>T (p.Gln169Leu) SNV Uncertain significance 323995 rs148370803 GRCh37: 17:4804915-4804915
GRCh38: 17:4901620-4901620
16 CHRNE NM_000080.4(CHRNE):c.1042G>A (p.Glu348Lys) SNV Uncertain significance 284315 rs757968612 GRCh37: 17:4802670-4802670
GRCh38: 17:4899375-4899375
17 CHRNE NM_000080.4(CHRNE):c.1222G>A (p.Ala408Thr) SNV Uncertain significance 1028049 GRCh37: 17:4802400-4802400
GRCh38: 17:4899105-4899105

UniProtKB/Swiss-Prot genetic disease variations for Myasthenic Syndrome, Congenital, 4b, Fast-Channel:

72
# Symbol AA change Variation ID SNP ID
1 CHRNE p.Pro141Leu VAR_000289 rs121909512
2 CHRNE p.Gly13Arg VAR_021213 rs372635387
3 CHRNE p.Ser163Leu VAR_021214 rs121909516
4 CHRNE p.Ala431Pro VAR_021215 rs121909517
5 CHRNE p.Trp75Arg VAR_071629 rs193919341

Expression for Myasthenic Syndrome, Congenital, 4b, Fast-Channel

Search GEO for disease gene expression data for Myasthenic Syndrome, Congenital, 4b, Fast-Channel.

Pathways for Myasthenic Syndrome, Congenital, 4b, Fast-Channel

GO Terms for Myasthenic Syndrome, Congenital, 4b, Fast-Channel

Sources for Myasthenic Syndrome, Congenital, 4b, 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
Content
Loading form....