MCID: MYS048
MIFTS: 19

Myasthenic Syndrome, Congenital, 3a, Slow-Channel

Categories: Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Myasthenic Syndrome, Congenital, 3a, Slow-Channel

MalaCards integrated aliases for Myasthenic Syndrome, Congenital, 3a, Slow-Channel:

Name: Myasthenic Syndrome, Congenital, 3a, Slow-Channel 57 75 29 6
Cms3a 57 12 75
Myasthenic Syndrome, Congenital, Type 3a, Slow-Channel 40
Congenital Myasthenic Syndrome 3a, Slow-Channel 12
Congenital Myasthenic Syndrome 3a 12

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
onset in infancy
progressive disorder
one patient has been reported (last curated april 2015)


HPO:

32
myasthenic syndrome, congenital, 3a, slow-channel:
Onset and clinical course infantile onset progressive
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Myasthenic Syndrome, Congenital, 3a, Slow-Channel

UniProtKB/Swiss-Prot : 75 Myasthenic syndrome, congenital, 3A, 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. CMS3A 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, 3a, Slow-Channel, is also known as cms3a. An important gene associated with Myasthenic Syndrome, Congenital, 3a, Slow-Channel is CHRND (Cholinergic Receptor Nicotinic Delta Subunit). Related phenotypes are ptosis and neonatal hypotonia

Disease Ontology : 12 A congenital myasthenic syndrome characterized by autosomal dominant inheritance of postsynaptic neuromuscular junction defects resulting in prolonged synaptic currents and early-onset progressive muscle weakness that has material basis in heterozygous mutation in the CHRND gene on chromosome 2q37.

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 AChR 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; acetylcholinesterase inhibitors and amifampridine should be avoided (summary by Engel et al., 2015). For a discussion of genetic heterogeneity of CMS, see CMS1A (601462). (616321)

Related Diseases for Myasthenic Syndrome, Congenital, 3a, Slow-Channel

Symptoms & Phenotypes for Myasthenic Syndrome, Congenital, 3a, Slow-Channel

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
ptosis

Abdomen Gastrointestinal:
swallowing difficulties

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

Muscle Soft Tissue:
inability to walk
easy fatigability
hypotonia, neonatal
generalized muscle weakness, severe
mild endplate myopathy
more
Respiratory:
respiratory insufficiency, episodic


Clinical features from OMIM:

616321

Human phenotypes related to Myasthenic Syndrome, Congenital, 3a, Slow-Channel:

32 (show all 7)
# Description HPO Frequency HPO Source Accession
1 ptosis 32 HP:0000508
2 neonatal hypotonia 32 HP:0001319
3 dysphagia 32 HP:0002015
4 respiratory insufficiency 32 HP:0002093
5 inability to walk 32 HP:0002540
6 generalized muscle weakness 32 HP:0003324
7 easy fatigability 32 HP:0003388

Drugs & Therapeutics for Myasthenic Syndrome, Congenital, 3a, Slow-Channel

Search Clinical Trials , NIH Clinical Center for Myasthenic Syndrome, Congenital, 3a, Slow-Channel

Genetic Tests for Myasthenic Syndrome, Congenital, 3a, Slow-Channel

Genetic tests related to Myasthenic Syndrome, Congenital, 3a, Slow-Channel:

# Genetic test Affiliating Genes
1 Myasthenic Syndrome, Congenital, 3a, Slow-Channel 29 CHRND

Anatomical Context for Myasthenic Syndrome, Congenital, 3a, Slow-Channel

Publications for Myasthenic Syndrome, Congenital, 3a, Slow-Channel

Variations for Myasthenic Syndrome, Congenital, 3a, Slow-Channel

UniProtKB/Swiss-Prot genetic disease variations for Myasthenic Syndrome, Congenital, 3a, Slow-Channel:

75
# Symbol AA change Variation ID SNP ID
1 CHRND p.Ser289Phe VAR_019566 rs121909502
2 CHRND p.Gln288Glu VAR_021212 rs41265127

ClinVar genetic disease variations for Myasthenic Syndrome, Congenital, 3a, Slow-Channel:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 CHRND NM_000751.2(CHRND): c.866C> T (p.Ser289Phe) single nucleotide variant Pathogenic rs121909502 GRCh37 Chromosome 2, 233396107: 233396107
2 CHRND NM_000751.2(CHRND): c.866C> T (p.Ser289Phe) single nucleotide variant Pathogenic rs121909502 GRCh38 Chromosome 2, 232531397: 232531397

Expression for Myasthenic Syndrome, Congenital, 3a, Slow-Channel

Search GEO for disease gene expression data for Myasthenic Syndrome, Congenital, 3a, Slow-Channel.

Pathways for Myasthenic Syndrome, Congenital, 3a, Slow-Channel

GO Terms for Myasthenic Syndrome, Congenital, 3a, Slow-Channel

Sources for Myasthenic Syndrome, Congenital, 3a, Slow-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
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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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