MCID: MYS051
MIFTS: 46

Myasthenic Syndrome, Congenital, 5

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Eye diseases

Aliases & Classifications for Myasthenic Syndrome, Congenital, 5

MalaCards integrated aliases for Myasthenic Syndrome, Congenital, 5:

Name: Myasthenic Syndrome, Congenital, 5 53 71
Endplate Acetylcholinesterase Deficiency 53 71 28 13 51 69
Engel Congenital Myasthenic Syndrome 53 12 71
Cms5 53 12 71
Ead 53 12 71
Myasthenic Syndrome, Congenital, Engel Type 53 71
Congenital Myasthenic Syndrome Type Ic 12 71
Congenital Myasthenic Syndrome 5 12 14
Cms Ic 12 71
Congenital Myasthenic Syndrome Type Ic, Formerly; Cms1c, Formerly 53
Congenital Myasthenic Syndrome Type Ic, Formerly 53
Endplate Acetylcholinesterase Deficiency; Ead 53
Congenital Myasthenic Syndrome Engel Type 12
End Plate Acetylcholinesterase Deficiency 12
End-Plate Acetylcholinesterase Deficiency 71
Synaptic Congenital Myasthenic Syndromes 55
Congenital Myasthenic Syndrome Type 1c 71
Cms Ic, Formerly 53
Cms1c, Formerly 53
Cms1c 71
Cmse 71

Characteristics:

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
onset usually in infancy
later childhood onset has been reported
phenotypic variation in severity and symptoms
no response or worsening with acetylcholinesterase inhibitors
symptoms progress with worsening myopathy


HPO:

31
myasthenic syndrome, congenital, 5:
Onset and clinical course infantile onset
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 53 603034
Disease Ontology 12 DOID:0110667
Orphanet 55 ORPHA98915
ICD10 via Orphanet 33 G70.2
MedGen 39 C1864233
MeSH 41 D020294
UMLS 69 C1864233

Summaries for Myasthenic Syndrome, Congenital, 5

OMIM : 53 Congenital myasthenic syndromes (CMS) are a group of inherited disorders affecting the neuromuscular junction. Patients present clinically with onset of variable muscle weakness between infancy and adulthood. These disorders have been classified according to the location of the defect: presynaptic, synaptic, and postsynaptic. Endplate acetylcholinesterase deficiency is an autosomal recessive congenital myasthenic syndrome characterized by a defect within the synapse at the neuromuscular junction (NMJ). Mutations in COLQ result in a deficiency of acetylcholinesterase (AChE), which causes prolonged synaptic currents and action potentials due to extended residence of acetylcholine in the synaptic space. Treatment with ephedrine may be beneficial; AChE inhibitors and amifampridine should be avoided (summary by Engel et al., 2015). For a discussion of genetic heterogeneity of CMS, see CMS1A (601462). (603034)

MalaCards based summary : Myasthenic Syndrome, Congenital, 5, also known as endplate acetylcholinesterase deficiency, is related to congenital myasthenic syndrome and cenani-lenz syndactyly syndrome, and has symptoms including ophthalmoparesis, generalized muscle weakness and ptosis. An important gene associated with Myasthenic Syndrome, Congenital, 5 is COLQ (Collagen Like Tail Subunit Of Asymmetric Acetylcholinesterase), and among its related pathways/superpathways are Signaling by FGFR2 in disease and RNA polymerase II transcribes snRNA genes. The drugs Ephedrine and Pseudoephedrine have been mentioned in the context of this disorder. Affiliated tissues include eye.

Disease Ontology : 12 A congenital myasthenic syndrome characterized by autosomal recessive inheritance of a defect within the synapse at the neuromuscular junction resulting in prolonged synaptic currents and action potentials that has material basis in homozygous or compound heterozygous mutation in the COLQ gene on chromosome 3p25.

UniProtKB/Swiss-Prot : 71 Myasthenic syndrome, congenital, 5: 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. CMS5 inheritance is autosomal recessive.

Related Diseases for Myasthenic Syndrome, Congenital, 5

Graphical network of the top 20 diseases related to Myasthenic Syndrome, Congenital, 5:



Diseases related to Myasthenic Syndrome, Congenital, 5

Symptoms & Phenotypes for Myasthenic Syndrome, Congenital, 5

Symptoms via clinical synopsis from OMIM:

53
HeadAndNeckEyes:
ophthalmoparesis
ptosis
slow, delayed pupillary light reflex

AbdomenGastrointestinal:
dysphagia
poor feeding due to muscle weakness

Respiratory:
respiratory insufficiency due to muscle weakness

MuscleSoftTissue:
muscle biopsy shows type 2 fiber atrophy
underdeveloped muscles
muscle biopsy shows endplate myopathy (see details under neurologic heading)

NeurologicPeripheralNervousSystem:
dysarthria
easy fatigability
hypotonia
limb weakness
prolonged miniature endplate potentials (mepp)
more
SkeletalSpine:
scoliosis
lordosis

Voice:
weak cry

Immunology:
absence of acetylcholine receptor (achr) autoantibodies


Clinical features from OMIM:

603034

Human phenotypes related to Myasthenic Syndrome, Congenital, 5:

31 (show all 21)
# Description HPO Frequency HPO Source Accession
1 ophthalmoparesis 31 HP:0000597
2 generalized muscle weakness 31 HP:0003324
3 ptosis 31 HP:0000508
4 dysarthria 31 HP:0001260
5 dysphagia 31 HP:0002015
6 respiratory insufficiency 31 HP:0002093
7 scoliosis 31 HP:0002650
8 hyperlordosis 31 HP:0003307
9 feeding difficulties in infancy 31 HP:0008872
10 decreased muscle mass 31 HP:0003199
11 respiratory insufficiency due to muscle weakness 31 HP:0002747
12 abnormality of the immune system 31 HP:0002715
13 weak cry 31 HP:0001612
14 fatigable weakness 31 HP:0003473
15 limb muscle weakness 31 HP:0003690
16 generalized hypotonia 31 HP:0001290
17 type 2 muscle fiber atrophy 31 HP:0003554
18 easy fatigability 31 HP:0003388
19 emg 31 HP:0003403
20 prolonged miniature endplate currents 31 HP:0003436
21 decreased size of nerve terminals 31 HP:0003443

UMLS symptoms related to Myasthenic Syndrome, Congenital, 5:


ophthalmoparesis

Drugs & Therapeutics for Myasthenic Syndrome, Congenital, 5

Drugs for Myasthenic Syndrome, Congenital, 5 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 12)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Ephedrine Approved Phase 1, Phase 2 299-42-3 9294
2
Pseudoephedrine Approved Phase 1, Phase 2 90-82-4 7028
3 Adrenergic Agents Phase 1, Phase 2
4 Anti-Asthmatic Agents Phase 1, Phase 2
5 Autonomic Agents Phase 1, Phase 2
6 Bronchodilator Agents Phase 1, Phase 2
7 Central Nervous System Stimulants Phase 1, Phase 2
8 Nasal Decongestants Phase 1, Phase 2
9 Neurotransmitter Agents Phase 1, Phase 2
10 Peripheral Nervous System Agents Phase 1, Phase 2
11 Respiratory System Agents Phase 1, Phase 2
12 Vasoconstrictor Agents Phase 1, Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Ephedrine for the Treatment of Congenital Myasthenia Unknown status NCT00541216 Phase 1, Phase 2 Ephedrine

Search NIH Clinical Center for Myasthenic Syndrome, Congenital, 5

Genetic Tests for Myasthenic Syndrome, Congenital, 5

Genetic tests related to Myasthenic Syndrome, Congenital, 5:

# Genetic test Affiliating Genes
1 Endplate Acetylcholinesterase Deficiency 28 COLQ

Anatomical Context for Myasthenic Syndrome, Congenital, 5

MalaCards organs/tissues related to Myasthenic Syndrome, Congenital, 5:

38
Eye

Publications for Myasthenic Syndrome, Congenital, 5

Articles related to Myasthenic Syndrome, Congenital, 5:

# Title Authors Year
1
Mechanism hypotheses for the electrophysiological manifestations of two cases of endplate acetylcholinesterase deficiency related congenital myasthenic syndrome. ( 29150079 )
2018
2
Mutations in the C-terminal domain of ColQ in endplate acetylcholinesterase deficiency compromise ColQ-MuSK interaction. ( 23553736 )
2013
3
Beneficial effects of albuterol in congenital endplate acetylcholinesterase deficiency and Dok-7 myasthenia. ( 21952943 )
2011
4
Evidence of a dosage effect and a physiological endplate acetylcholinesterase deficiency in the first mouse models mimicking Schwartz-Jampel syndrome neuromyotonia. ( 18647752 )
2008
5
Congenital endplate acetylcholinesterase deficiency responsive to ephedrine. ( 16009904 )
2005
6
Two novel mutations in the COLQ gene cause endplate acetylcholinesterase deficiency. ( 12609505 )
2003
7
Human endplate acetylcholinesterase deficiency caused by mutations in the collagen-like tail subunit (ColQ) of the asymmetric enzyme. ( 9689136 )
1998
8
Treatment of congenital endplate acetylcholinesterase deficiency by neuromuscular blockade. ( 8807428 )
1996
9
Congenital endplate acetylcholinesterase deficiency. ( 8390325 )
1993

Variations for Myasthenic Syndrome, Congenital, 5

UniProtKB/Swiss-Prot genetic disease variations for Myasthenic Syndrome, Congenital, 5:

71
# Symbol AA change Variation ID SNP ID
1 COLQ p.Pro59Gln VAR_010133
2 COLQ p.Asp342Glu VAR_010134 rs758554049
3 COLQ p.Arg410Gln VAR_010135 rs1025361623Myasthenic
4 COLQ p.Tyr430Ser VAR_010136 rs121908923
5 COLQ p.Cys444Tyr VAR_010137
6 COLQ p.Ile337Thr VAR_071710

ClinVar genetic disease variations for Myasthenic Syndrome, Congenital, 5:

6 (show all 12)
# Gene Variation Type Significance SNP ID Assembly Location
1 COLQ COLQ, 215-BP DEL, NT107 deletion Pathogenic
2 COLQ NM_005677.3(COLQ): c.640G> T (p.Glu214Ter) single nucleotide variant Pathogenic rs104893733 GRCh37 Chromosome 3, 15512120: 15512120
3 COLQ NM_005677.3(COLQ): c.506C> G (p.Ser169Ter) single nucleotide variant Pathogenic rs104893734 GRCh37 Chromosome 3, 15516954: 15516954
4 COLQ NM_005677.3(COLQ): c.844A> T (p.Arg282Ter) single nucleotide variant Pathogenic rs121908922 GRCh37 Chromosome 3, 15499803: 15499803
5 COLQ NM_005677.3(COLQ): c.1082delC (p.Pro361Leufs) deletion Pathogenic rs769982050 GRCh37 Chromosome 3, 15497519: 15497519
6 COLQ NM_005677.3(COLQ): c.788dupC (p.Pro265Alafs) duplication Pathogenic rs759911990 GRCh37 Chromosome 3, 15507874: 15507874
7 COLQ NM_005677.3(COLQ): c.1289A> C (p.Tyr430Ser) single nucleotide variant Pathogenic rs121908923 GRCh37 Chromosome 3, 15495345: 15495345
8 COLQ NM_005677.3(COLQ): c.943C> T (p.Arg315Ter) single nucleotide variant Pathogenic rs121908924 GRCh37 Chromosome 3, 15499704: 15499704
9 COLQ COLQ, IVS16DS, A-G, +3 single nucleotide variant Pathogenic
10 COLQ NM_005677.3(COLQ): c.718G> T (p.Gly240Ter) single nucleotide variant Pathogenic rs104893735 GRCh37 Chromosome 3, 15507944: 15507944
11 COLQ NM_005677.3(COLQ): c.529-2A> G single nucleotide variant Pathogenic rs755236236 GRCh37 Chromosome 3, 15516460: 15516460
12 COLQ NM_005677.3(COLQ): c.157dup (p.Leu53Profs) duplication Pathogenic GRCh37 Chromosome 3, 15531094: 15531094

Expression for Myasthenic Syndrome, Congenital, 5

Search GEO for disease gene expression data for Myasthenic Syndrome, Congenital, 5.

Pathways for Myasthenic Syndrome, Congenital, 5

GO Terms for Myasthenic Syndrome, Congenital, 5

Cellular components related to Myasthenic Syndrome, Congenital, 5 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 DNA-directed RNA polymerase II, core complex GO:0005665 9.33 POLR2D POLR2E POLR2G
2 basal lamina GO:0005605 9.13 ACHE COLQ LAMB2
3 synaptic cleft GO:0043083 8.8 ACHE COLQ LAMB2

Biological processes related to Myasthenic Syndrome, Congenital, 5 according to GeneCards Suite gene sharing:

(show all 13)
# Name GO ID Score Top Affiliating Genes
1 transcription elongation from RNA polymerase II promoter GO:0006368 9.69 POLR2D POLR2E POLR2G
2 fibroblast growth factor receptor signaling pathway GO:0008543 9.67 POLR2D POLR2E POLR2G
3 regulation of gene silencing by miRNA GO:0060964 9.65 POLR2D POLR2E POLR2G
4 transcription-coupled nucleotide-excision repair GO:0006283 9.58 POLR2D POLR2E POLR2G
5 snRNA transcription by RNA polymerase II GO:0042795 9.54 POLR2D POLR2E POLR2G
6 positive regulation of translational initiation GO:0045948 9.52 POLR2D POLR2G
7 somatic stem cell population maintenance GO:0035019 9.5 POLR2D POLR2E POLR2G
8 neurotransmitter catabolic process GO:0042135 9.46 ACHE COLQ
9 phosphorelay signal transduction system GO:0000160 9.43 KCNH1 KCNH2
10 RNA metabolic process GO:0016070 9.43 POLR2D POLR2E POLR2G
11 7-methylguanosine mRNA capping GO:0006370 9.33 POLR2D POLR2E POLR2G
12 positive regulation of viral transcription GO:0050434 9.13 POLR2D POLR2E POLR2G
13 acetylcholine catabolic process in synaptic cleft GO:0001507 8.62 ACHE COLQ

Molecular functions related to Myasthenic Syndrome, Congenital, 5 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 translation initiation factor binding GO:0031369 9.26 POLR2D POLR2G
2 delayed rectifier potassium channel activity GO:0005251 9.16 KCNH1 KCNH2
3 phosphorelay sensor kinase activity GO:0000155 8.96 KCNH1 KCNH2
4 DNA-directed 5-3 RNA polymerase activity GO:0003899 8.8 POLR2D POLR2E POLR2G

Sources for Myasthenic Syndrome, Congenital, 5

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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