MCID: MYS060
MIFTS: 21

Myasthenic Syndrome, Congenital, 4b, Fast-Channel

Categories: Genetic 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 75 29 6
Cms4b 57 12 75
Myasthenic Syndrome, Congenital, Type 4b, Fast-Channel 40
Congenital Myasthenic Syndrome 4b Fast-Channel 12
Congenital Myasthenic Syndrome 4b 12

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

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


HPO:

32
myasthenic syndrome, congenital, 4b, fast-channel:
Onset and clinical course infantile onset
Inheritance autosomal recessive inheritance


Classifications:



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

UniProtKB/Swiss-Prot : 75 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, 4a, slow-channel and congenital myasthenic syndrome. An important gene associated with Myasthenic Syndrome, Congenital, 4b, Fast-Channel is CHRNE (Cholinergic Receptor Nicotinic Epsilon Subunit). Related phenotypes are ptosis and respiratory insufficiency

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)

Related Diseases for Myasthenic Syndrome, Congenital, 4b, 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, 4b, Fast-Channel via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 myasthenic syndrome, congenital, 4a, slow-channel 9.2 C17orf107 CHRNE
2 congenital myasthenic syndrome 9.0 C17orf107 CHRNE

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

Symptoms via clinical synopsis from OMIM:

57
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

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

32 (show all 8)
# Description HPO Frequency HPO Source Accession
1 ptosis 32 HP:0000508
2 respiratory insufficiency 32 HP:0002093
3 facial palsy 32 HP:0010628
4 neonatal hypotonia 32 HP:0001319
5 feeding difficulties 32 HP:0011968
6 neck muscle weakness 32 HP:0000467
7 ophthalmoplegia 32 HP:0000602
8 easy fatigability 32 HP:0003388

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

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

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

75
# 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

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

6
# Gene Variation Type Significance SNP ID Assembly Location
1 CHRNE NM_000080.3(CHRNE): c.422C> T (p.Pro141Leu) single nucleotide variant Pathogenic rs121909512 GRCh37 Chromosome 17, 4805305: 4805305
2 CHRNE NM_000080.3(CHRNE): c.422C> T (p.Pro141Leu) single nucleotide variant Pathogenic rs121909512 GRCh38 Chromosome 17, 4902010: 4902010
3 CHRNE NM_000080.3(CHRNE): c.1291G> C (p.Ala431Pro) single nucleotide variant Pathogenic rs121909517 GRCh37 Chromosome 17, 4802331: 4802331
4 CHRNE NM_000080.3(CHRNE): c.1291G> C (p.Ala431Pro) single nucleotide variant Pathogenic rs121909517 GRCh38 Chromosome 17, 4899036: 4899036
5 CHRNE NM_000080.3(CHRNE): c.223T> C (p.Trp75Arg) single nucleotide variant Pathogenic rs193919341 GRCh37 Chromosome 17, 4805756: 4805756
6 CHRNE NM_000080.3(CHRNE): c.223T> C (p.Trp75Arg) single nucleotide variant Pathogenic rs193919341 GRCh38 Chromosome 17, 4902461: 4902461
7 CHRNE NM_000080.3(CHRNE): c.1093delG (p.Ala365Profs) deletion Pathogenic rs886043239 GRCh37 Chromosome 17, 4802619: 4802619
8 CHRNE NM_000080.3(CHRNE): c.1093delG (p.Ala365Profs) deletion Pathogenic rs886043239 GRCh38 Chromosome 17, 4899324: 4899324

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

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7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
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31 HMDB
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34 ICD10 via Orphanet
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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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