MCID: MYS051
MIFTS: 45

Myasthenic Syndrome, Congenital, 5

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

Aliases & Classifications for Myasthenic Syndrome, Congenital, 5

MalaCards integrated aliases for Myasthenic Syndrome, Congenital, 5:

Name: Myasthenic Syndrome, Congenital, 5 54 71
Endplate Acetylcholinesterase Deficiency 71 29 13 52 69
Congenital Myasthenic Syndrome Type Ic 12 71
Engel Congenital Myasthenic Syndrome 12 71
Congenital Myasthenic Syndrome 5 12 14
Cms Ic 12 71
Cms5 12 71
Ead 12 71
Myasthenic Syndrome, Congenital, Engel Type 71
Congenital Myasthenic Syndrome Engel Type 12
End Plate Acetylcholinesterase Deficiency 12
End-Plate Acetylcholinesterase Deficiency 71
Synaptic Congenital Myasthenic Syndromes 56
Congenital Myasthenic Syndrome Type 1c 71
Cms1c 71
Cmse 71

Characteristics:

OMIM:

54
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:

32
myasthenic syndrome, congenital, 5:
Onset and clinical course infantile onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Myasthenic Syndrome, Congenital, 5

OMIM : 54
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 sclerosteosis 2 and congenital myasthenic syndrome, and has symptoms including scoliosis, dysphagia and dysarthria. 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, and related phenotype is Decreased shRNA abundance (Z-score < -2).

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.

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.

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:

54

Skeletal- Spine:
scoliosis
lordosis

Abdomen- Gastroin testinal:
dysphagia
poor feeding due to muscle weakness

Respiratory:
respiratory insufficiency due to muscle weakness

Voice:
weak cry

Neurologic- Peripheral Nervous System:
hypotonia
dysarthria
easy fatigability
prolonged miniature endplate potentials (mepp)
prolonged miniature endplate currents (mepc)
more
Head And Neck- Eyes:
ptosis
ophthalmoparesis
slow, delayed pupillary light reflex

Immunology:
absence of acetylcholine receptor (achr) autoantibodies

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


Clinical features from OMIM:

603034

Human phenotypes related to Myasthenic Syndrome, Congenital, 5:

32 (show all 21)
id Description HPO Frequency HPO Source Accession
1 scoliosis 32 HP:0002650
2 dysphagia 32 HP:0002015
3 dysarthria 32 HP:0001260
4 ptosis 32 HP:0000508
5 easy fatigability 32 HP:0003388
6 respiratory insufficiency due to muscle weakness 32 HP:0002747
7 respiratory insufficiency 32 HP:0002093
8 hyperlordosis 32 HP:0003307
9 muscular hypotonia 32 HP:0001252
10 feeding difficulties in infancy 32 HP:0008872
11 ophthalmoparesis 32 HP:0000597
12 generalized muscle weakness 32 HP:0003324
13 weak cry 32 HP:0001612
14 decreased muscle mass 32 HP:0003199
15 limb muscle weakness 32 HP:0003690
16 abnormality of the immune system 32 HP:0002715
17 fatigable weakness 32 HP:0003473
18 emg 32 HP:0003403
19 type 2 muscle fiber atrophy 32 HP:0003554
20 prolonged miniature endplate currents 32 HP:0003436
21 decreased size of nerve terminals 32 HP:0003443

UMLS symptoms related to Myasthenic Syndrome, Congenital, 5:


ophthalmoparesis

GenomeRNAi Phenotypes related to Myasthenic Syndrome, Congenital, 5 according to GeneCards Suite gene sharing:

26
id Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-104 9.7 RPL22
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-111 9.7 POLR2E
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-112 9.7 POLR2G
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-119 9.7 POLR2D
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-139 9.7 POLR2D POLR2G
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-165 9.7 POLR2D
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-173 9.7 POLR2D POLR2G
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-20 9.7 RPL22
9 Decreased shRNA abundance (Z-score < -2) GR00366-A-203 9.7 POLR2G
10 Decreased shRNA abundance (Z-score < -2) GR00366-A-209 9.7 POLR2D
11 Decreased shRNA abundance (Z-score < -2) GR00366-A-211 9.7 POLR2E
12 Decreased shRNA abundance (Z-score < -2) GR00366-A-213 9.7 POLR2D
13 Decreased shRNA abundance (Z-score < -2) GR00366-A-26 9.7 RPL22 POLR2D POLR2E POLR2G
14 Decreased shRNA abundance (Z-score < -2) GR00366-A-33 9.7 RPL22
15 Decreased shRNA abundance (Z-score < -2) GR00366-A-61 9.7 POLR2D
16 Decreased shRNA abundance (Z-score < -2) GR00366-A-65 9.7 RPL22 POLR2E
17 Decreased shRNA abundance (Z-score < -2) GR00366-A-89 9.7 POLR2E
18 Decreased shRNA abundance (Z-score < -2) GR00366-A-95 9.7 POLR2G

Drugs & Therapeutics for Myasthenic Syndrome, Congenital, 5

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

(show all 15)
id 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
13
4-Aminopyridine Approved 504-24-5 1727
14 3,4-diaminopyridine
15 Potassium Channel Blockers

Interventional clinical trials:


id Name Status NCT ID Phase Drugs
1 Ephedrine for the Treatment of Congenital Myasthenia Unknown status NCT00541216 Phase 1, Phase 2 Ephedrine
2 Treatment of Lambert-Eaton Myasthenic Syndrome (LEMS) With 3, 4 DAP No longer available NCT01378546 3,4-diaminopyridine

Search NIH Clinical Center for Myasthenic Syndrome, Congenital, 5

Genetic Tests for Myasthenic Syndrome, Congenital, 5

Genetic tests related to Myasthenic Syndrome, Congenital, 5:

id Genetic test Affiliating Genes
1 Endplate Acetylcholinesterase Deficiency 29

Anatomical Context for Myasthenic Syndrome, Congenital, 5

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

39
Eye

Publications for Myasthenic Syndrome, Congenital, 5

Variations for Myasthenic Syndrome, Congenital, 5

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

71
id 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
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 11)
id 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

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:

id 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 14)
id Name GO ID Score Top Affiliating Genes
1 transcription initiation from RNA polymerase II promoter GO:0006367 9.71 POLR2D POLR2E POLR2G
2 transcription elongation from RNA polymerase II promoter GO:0006368 9.69 POLR2D POLR2E POLR2G
3 fibroblast growth factor receptor signaling pathway GO:0008543 9.67 POLR2D POLR2E POLR2G
4 regulation of gene silencing by miRNA GO:0060964 9.65 POLR2D POLR2E POLR2G
5 transcription-coupled nucleotide-excision repair GO:0006283 9.61 POLR2D POLR2E POLR2G
6 snRNA transcription from RNA polymerase II promoter GO:0042795 9.54 POLR2D POLR2E POLR2G
7 positive regulation of translational initiation GO:0045948 9.52 POLR2D POLR2G
8 somatic stem cell population maintenance GO:0035019 9.5 POLR2D POLR2E POLR2G
9 neurotransmitter catabolic process GO:0042135 9.46 ACHE COLQ
10 RNA metabolic process GO:0016070 9.43 POLR2D POLR2E POLR2G
11 phosphorelay signal transduction system GO:0000160 9.4 KCNH1 KCNH2
12 7-methylguanosine mRNA capping GO:0006370 9.33 POLR2D POLR2E POLR2G
13 positive regulation of viral transcription GO:0050434 9.13 POLR2D POLR2E POLR2G
14 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:

id 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
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
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46 NCI
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48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 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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