CMS3A
MCID: MYS048
MIFTS: 35

Myasthenic Syndrome, Congenital, 3a, Slow-Channel (CMS3A)

Categories: Genetic diseases, Muscle 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 72 29 6
Cms3a 57 12 72
Congenital Myasthenic Syndrome 3a 12 15
Myasthenic Syndrome, Congenital, Type 3a, Slow-Channel 39
Congenital Myasthenic Syndrome 3a, Slow-Channel 12

Characteristics:

OMIM®:

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

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


HPO:

31
myasthenic syndrome, congenital, 3a, slow-channel:
Inheritance autosomal dominant inheritance
Onset and clinical course infantile onset progressive


Classifications:



External Ids:

Disease Ontology 12 DOID:0110666
OMIM® 57 616321
OMIM Phenotypic Series 57 PS601462
MeSH 44 D020294

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

UniProtKB/Swiss-Prot : 72 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, also known as cms3a, is related to cerebellar medulloblastoma and melanoma-associated retinopathy. An important gene associated with Myasthenic Syndrome, Congenital, 3a, Slow-Channel is CHRND (Cholinergic Receptor Nicotinic Delta Subunit), and among its related pathways/superpathways are Metabolism of fat-soluble vitamins and Visual Cycle in Retinal Rods. Related phenotypes are ptosis and dysphagia

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) (Updated 05-Apr-2021)

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

Diseases in the Slow-Channel Congenital Myasthenic Syndrome family:

Myasthenic Syndrome, Congenital, 1a, Slow-Channel Myasthenic Syndrome, Congenital, 4a, Slow-Channel
Myasthenic Syndrome, Congenital, 2a, Slow-Channel Myasthenic Syndrome, Congenital, 3a, Slow-Channel

Diseases related to Myasthenic Syndrome, Congenital, 3a, Slow-Channel via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 31)
# Related Disease Score Top Affiliating Genes
1 cerebellar medulloblastoma 10.0 SAG CHRND
2 melanoma-associated retinopathy 9.9 SAG RHO
3 retinal vasculitis 9.9 SAG ARR3
4 pineocytoma 9.9 SAG RHO
5 cancer-associated retinopathy 9.9 SAG RHO
6 diabetes insipidus, nephrogenic, autosomal 9.8 SAG RHO
7 abnormal threshold of rods 9.8 SAG GRK1
8 uveal disease 9.8 SAG RHO
9 night blindness, congenital stationary, type 2a 9.7 GRK1 ARR3
10 retinoschisis 1, x-linked, juvenile 9.6 RHO GRK1
11 usher syndrome type 2 9.5 RHO GRK1
12 prolonged electroretinal response suppression 9.5 RHO GRK7 GRK1
13 oguchi disease 9.5 SAG RHO GRK1
14 fundus albipunctatus 9.5 SAG RHO GRK1
15 achromatopsia 9.5 RHO GRK1 ARR3
16 cone dystrophy 9.4 SAG RHO GRK1
17 stargardt disease 9.4 RHO GRK1
18 oguchi disease 1 9.3 SAG GRK7 GRK1 ARR3
19 oguchi disease 2 9.3 SAG GRK7 GRK1 ARR3
20 enhanced s-cone syndrome 9.3 RHO GRK7 GRK1 ARR3
21 night blindness 9.3 SAG RHO GRK7 GRK1
22 leber congenital amaurosis 1 9.2 RHO GRK7 GRK1 ARR3
23 usher syndrome 9.2 RHO GRK7 GRK1 ARR3
24 macular degeneration, age-related, 1 9.2 SAG RHO GRK1 ARR3
25 retinal degeneration 9.2 SAG RHO GRK1 ARR3
26 cone-rod dystrophy 2 9.1 SAG RHO GRK1 ARR3
27 eye degenerative disease 9.0 SAG RHO GRK7 GRK1 ARR3
28 congenital stationary night blindness 9.0 SAG RHO GRK7 GRK1 ARR3
29 leber plus disease 9.0 SAG RHO GRK7 GRK1 ARR3
30 fundus dystrophy 9.0 SAG RHO GRK7 GRK1 ARR3
31 retinitis pigmentosa 8.9 SAG RHO GRK7 GRK1 ARR3

Graphical network of the top 20 diseases related to Myasthenic Syndrome, Congenital, 3a, Slow-Channel:



Diseases related to Myasthenic Syndrome, Congenital, 3a, Slow-Channel

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

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

31 (show all 8)
# Description HPO Frequency HPO Source Accession
1 ptosis 31 HP:0000508
2 dysphagia 31 HP:0002015
3 respiratory insufficiency 31 HP:0002093
4 neonatal hypotonia 31 HP:0001319
5 myopathy 31 HP:0003198
6 easy fatigability 31 HP:0003388
7 generalized muscle weakness 31 HP:0003324
8 inability to walk 31 HP:0002540

Symptoms via clinical synopsis from OMIM®:

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

Abdomen Gastrointestinal:
swallowing difficulties

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

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

Clinical features from OMIM®:

616321 (Updated 05-Apr-2021)

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

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

# Title Authors PMID Year
1
Novel delta subunit mutation in slow-channel syndrome causes severe weakness by novel mechanisms. 57 6
11782989 2002
2
Congenital myasthenic syndromes: pathogenesis, diagnosis, and treatment. 57
25792100 2015

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

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

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 CHRND NM_000751.3(CHRND):c.866C>T (p.Ser289Phe) SNV Pathogenic 18363 rs121909502 GRCh37: 2:233396107-233396107
GRCh38: 2:232531397-232531397
2 CHRND NM_000751.3(CHRND):c.1181A>C (p.Lys394Thr) SNV Uncertain significance 548627 rs1553575390 GRCh37: 2:233398774-233398774
GRCh38: 2:232534064-232534064
3 CHRND NM_000751.3(CHRND):c.1220G>A (p.Arg407Gln) SNV Uncertain significance 286380 rs563035306 GRCh37: 2:233398813-233398813
GRCh38: 2:232534103-232534103
4 CHRND NM_000751.3(CHRND):c.1105C>T (p.Pro369Ser) SNV Uncertain significance 193603 rs2229194 GRCh37: 2:233398698-233398698
GRCh38: 2:232533988-232533988
5 CHRND NM_000751.3(CHRND):c.919C>T (p.Pro307Ser) SNV Uncertain significance 281423 rs142063328 GRCh37: 2:233396160-233396160
GRCh38: 2:232531450-232531450
6 CHRND NM_000751.3(CHRND):c.727C>T (p.Arg243Cys) SNV Uncertain significance 283138 rs201733876 GRCh37: 2:233394756-233394756
GRCh38: 2:232530046-232530046
7 CHRND NM_000751.3(CHRND):c.127C>T (p.Arg43Trp) SNV Uncertain significance 420109 rs55868108 GRCh37: 2:233391313-233391313
GRCh38: 2:232526603-232526603
8 CHRND NM_000751.3(CHRND):c.136G>A (p.Ala46Thr) SNV Uncertain significance 426311 rs1085307559 GRCh37: 2:233391322-233391322
GRCh38: 2:232526612-232526612
9 CHRND NM_000751.3(CHRND):c.218T>C (p.Leu73Pro) SNV Uncertain significance 1033120 GRCh37: 2:233392130-233392130
GRCh38: 2:232527420-232527420

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

72
# Symbol AA change Variation ID SNP ID
1 CHRND p.Ser289Phe VAR_019566 rs121909502

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

Cellular components related to Myasthenic Syndrome, Congenital, 3a, Slow-Channel according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cell projection GO:0042995 9.56 SAG RHO GRK1 ARR3
2 photoreceptor inner segment GO:0001917 9.33 SAG RHO ARR3
3 photoreceptor disc membrane GO:0097381 9.13 RHO GRK7 GRK1
4 photoreceptor outer segment GO:0001750 8.92 SAG RHO GRK1 ARR3

Biological processes related to Myasthenic Syndrome, Congenital, 3a, Slow-Channel according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 signal transduction GO:0007165 9.73 SAG RHO GRK7 GRK1 CHRND ARR3
2 response to stimulus GO:0050896 9.62 RHO GRK7 GRK1 ARR3
3 protein phosphorylation GO:0006468 9.58 RHO GRK7 GRK1
4 visual perception GO:0007601 9.46 RHO GRK7 GRK1 ARR3
5 G protein-coupled receptor internalization GO:0002031 9.37 SAG ARR3
6 rhodopsin mediated signaling pathway GO:0016056 9.13 SAG RHO GRK1
7 regulation of rhodopsin mediated signaling pathway GO:0022400 8.92 SAG RHO GRK7 GRK1

Molecular functions related to Myasthenic Syndrome, Congenital, 3a, Slow-Channel according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 G protein-coupled receptor binding GO:0001664 9.32 SAG ARR3
2 phosphoprotein binding GO:0051219 9.26 SAG ARR3
3 G protein-coupled receptor kinase activity GO:0004703 9.16 GRK7 GRK1
4 opsin binding GO:0002046 8.96 SAG ARR3
5 rhodopsin kinase activity GO:0050254 8.62 GRK7 GRK1

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