CMS21
MCID: MYS069
MIFTS: 35

Myasthenic Syndrome, Congenital, 21, Presynaptic (CMS21)

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

Aliases & Classifications for Myasthenic Syndrome, Congenital, 21, Presynaptic

MalaCards integrated aliases for Myasthenic Syndrome, Congenital, 21, Presynaptic:

Name: Myasthenic Syndrome, Congenital, 21, Presynaptic 57 72 29 6
Cms21 57 12 72
Congenital Myasthenic Syndrome 21 12 15
Congenital Myasthenic Syndrome 21, Presynaptic 12

Characteristics:

OMIM®:

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

Miscellaneous:
onset in early infancy
two unrelated patients have been reported (last curated december 2016)
favorable response to pyridostigmine


HPO:

31
myasthenic syndrome, congenital, 21, presynaptic:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Myasthenic Syndrome, Congenital, 21, Presynaptic

UniProtKB/Swiss-Prot : 72 Myasthenic syndrome, congenital, 21, presynaptic: 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. CMS21 is an autosomal recessive, pre-synaptic form characterized by ptosis, ophthalmoplegia, fatigable weakness, apneic crises, and deterioration of symptoms in cold water. Learning difficulties and left ventricular dysfunction may be present in some patients.

MalaCards based summary : Myasthenic Syndrome, Congenital, 21, Presynaptic, also known as cms21, is related to tendinosis and sclerosteosis 2. An important gene associated with Myasthenic Syndrome, Congenital, 21, Presynaptic is SLC18A3 (Solute Carrier Family 18 Member A3), and among its related pathways/superpathways are Synthesis of substrates in N-glycan biosythesis and Agrin Interactions at Neuromuscular Junction. Related phenotypes are ptosis and nystagmus

Disease Ontology : 12 A congenital myasthenic syndrome characterized by autosomal recessive inheritance of hypotonia, apneas, and feeding difficulties that has material basis in homozygous or compound heterozygous mutation in the SLC18A3 gene on chromosome 10q11.

More information from OMIM: 617239 PS601462

Related Diseases for Myasthenic Syndrome, Congenital, 21, Presynaptic

Diseases in the Presynaptic Congenital Myasthenic Syndromes family:

Myasthenic Syndrome, Congenital, 6, Presynaptic Myasthenic Syndrome, Congenital, 7, Presynaptic
Myasthenic Syndrome, Congenital, 20, Presynaptic Myasthenic Syndrome, Congenital, 21, Presynaptic
Myasthenic Syndrome, Congenital, 23, Presynaptic Myasthenic Syndrome, Congenital, 24, Presynaptic
Myasthenic Syndrome, Congenital, 25, Presynaptic

Diseases related to Myasthenic Syndrome, Congenital, 21, Presynaptic via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 22)
# Related Disease Score Top Affiliating Genes
1 tendinosis 10.1 SLC18A3 CHAT
2 sclerosteosis 2 10.0 RAPSN DOK7
3 congenital myasthenic syndrome associated with acetylcholine receptor deficiency 9.9 RAPSN CHAT
4 neonatal myasthenia gravis 9.8 COLQ AGRN
5 congenital myasthenic syndromes with glycosylation defect 9.8 GFPT1 DPAGT1 ALG14
6 myasthenic syndrome, congenital, 5 9.8 RAPSN DOK7 COLQ
7 myasthenic syndrome, congenital, 4c, associated with acetylcholine receptor deficiency 9.8 RAPSN GFPT1 CHAT
8 fetal akinesia deformation sequence 1 9.8 SLC18A3 RAPSN DOK7
9 presynaptic congenital myasthenic syndromes 9.8 SLC18A3 CHAT AGRN
10 myasthenic syndrome, congenital, 19 9.8 SLC18A3 RAPSN DOK7 CHAT
11 ocular motility disease 9.7 RAPSN COLQ
12 myasthenic syndrome, congenital, 13 9.7 RAPSN DPAGT1 DOK7 COLQ
13 postsynaptic congenital myasthenic syndromes 9.6 RAPSN DOK7 AGRN
14 cenani-lenz syndactyly syndrome 9.6 RAPSN DOK7 AGRN
15 autoimmune disease of peripheral nervous system 9.6 RAPSN AGRN
16 ptosis 9.6 SLC18A3 RAPSN DOK7 COLQ CHAT
17 muscular dystrophy, congenital, lmna-related 9.4 RAPSN DOK7 COLQ AGRN
18 walker-warburg syndrome 9.4 GFPT1 DPAGT1 ALG14 AGRN
19 peripheral nervous system disease 9.3 RAPSN DOK7 COLQ CHAT AGRN
20 neuromuscular junction disease 8.6 RAPSN GFPT1 DPAGT1 DOK7 COLQ CHAT
21 neuromuscular disease 8.6 RAPSN GFPT1 DPAGT1 DOK7 COLQ CHAT
22 congenital myasthenic syndrome 8.5 SLC18A3 RAPSN GFPT1 DPAGT1 DOK7 COLQ

Graphical network of the top 20 diseases related to Myasthenic Syndrome, Congenital, 21, Presynaptic:



Diseases related to Myasthenic Syndrome, Congenital, 21, Presynaptic

Symptoms & Phenotypes for Myasthenic Syndrome, Congenital, 21, Presynaptic

Human phenotypes related to Myasthenic Syndrome, Congenital, 21, Presynaptic:

31 (show all 12)
# Description HPO Frequency HPO Source Accession
1 ptosis 31 HP:0000508
2 nystagmus 31 HP:0000639
3 facial palsy 31 HP:0010628
4 respiratory insufficiency 31 HP:0002093
5 fatigue 31 HP:0012378
6 ophthalmoplegia 31 HP:0000602
7 apnea 31 HP:0002104
8 feeding difficulties 31 HP:0011968
9 knee flexion contracture 31 HP:0006380
10 generalized hypotonia 31 HP:0001290
11 difficulty walking 31 HP:0002355
12 exercise intolerance 31 HP:0003546

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Head And Neck Eyes:
ptosis
ophthalmoplegia
nystagmus (patient b)

Muscle Soft Tissue:
fatigue
exercise intolerance
hypotonia
muscle weakness, upper and lower limbs
decremental response to repetitive nerve stimulation
more
Head And Neck Face:
facial weakness

Cardiovascular Heart:
reduced left ventricular function, mild (patient a)

Respiratory:
respiratory insufficiency
apneic episodes

Abdomen Gastrointestinal:
feeding difficulties

Skeletal Limbs:
knee contractures (patient b)

Neurologic Central Nervous System:
learning disabilities (patient a)

Clinical features from OMIM®:

617239 (Updated 05-Apr-2021)

MGI Mouse Phenotypes related to Myasthenic Syndrome, Congenital, 21, Presynaptic:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 mortality/aging MP:0010768 9.81 AGRN ALG14 CHAT DOK7 DPAGT1 GFPT1
2 muscle MP:0005369 9.43 AGRN CHAT DOK7 GFPT1 RAPSN SLC18A3
3 respiratory system MP:0005388 9.02 AGRN CHAT DOK7 PLG RAPSN

Drugs & Therapeutics for Myasthenic Syndrome, Congenital, 21, Presynaptic

Search Clinical Trials , NIH Clinical Center for Myasthenic Syndrome, Congenital, 21, Presynaptic

Genetic Tests for Myasthenic Syndrome, Congenital, 21, Presynaptic

Genetic tests related to Myasthenic Syndrome, Congenital, 21, Presynaptic:

# Genetic test Affiliating Genes
1 Myasthenic Syndrome, Congenital, 21, Presynaptic 29 SLC18A3

Anatomical Context for Myasthenic Syndrome, Congenital, 21, Presynaptic

Publications for Myasthenic Syndrome, Congenital, 21, Presynaptic

Articles related to Myasthenic Syndrome, Congenital, 21, Presynaptic:

# Title Authors PMID Year
1
Variants in SLC18A3, vesicular acetylcholine transporter, cause congenital myasthenic syndrome. 6 57
27590285 2016
2
Dysautonomia due to reduced cholinergic neurotransmission causes cardiac remodeling and heart failure. 57
20123977 2010

Variations for Myasthenic Syndrome, Congenital, 21, Presynaptic

ClinVar genetic disease variations for Myasthenic Syndrome, Congenital, 21, Presynaptic:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 CHAT , SLC18A3 NM_003055.3(SLC18A3):c.1192G>C (p.Asp398His) SNV Pathogenic 372160 rs1057517666 GRCh37: 10:50819978-50819978
GRCh38: 10:49611932-49611932
2 CHAT , SLC18A3 NM_003055.3(SLC18A3):c.557G>C (p.Gly186Ala) SNV Uncertain significance 372159 rs1057517665 GRCh37: 10:50819343-50819343
GRCh38: 10:49611297-49611297
3 CHAT , SLC18A3 NM_003055.3(SLC18A3):c.1093G>C (p.Ala365Pro) SNV Uncertain significance 1029501 GRCh37: 10:50819879-50819879
GRCh38: 10:49611833-49611833
4 CHAT , SLC18A3 NM_003055.3(SLC18A3):c.151A>G (p.Met51Val) SNV Uncertain significance 1032110 GRCh37: 10:50818937-50818937
GRCh38: 10:49610891-49610891
5 CHAT , SLC18A3 NM_003055.3(SLC18A3):c.85C>T (p.Arg29Trp) SNV Uncertain significance 732977 rs8187734 GRCh37: 10:50818871-50818871
GRCh38: 10:49610825-49610825
6 CHAT , SLC18A3 NM_003055.3(SLC18A3):c.88C>T (p.Arg30Trp) SNV Uncertain significance 1032111 GRCh37: 10:50818874-50818874
GRCh38: 10:49610828-49610828

UniProtKB/Swiss-Prot genetic disease variations for Myasthenic Syndrome, Congenital, 21, Presynaptic:

72
# Symbol AA change Variation ID SNP ID
1 SLC18A3 p.Gly186Ala VAR_078030 rs105751766
2 SLC18A3 p.Asp398His VAR_078031 rs105751766

Expression for Myasthenic Syndrome, Congenital, 21, Presynaptic

Search GEO for disease gene expression data for Myasthenic Syndrome, Congenital, 21, Presynaptic.

Pathways for Myasthenic Syndrome, Congenital, 21, Presynaptic

GO Terms for Myasthenic Syndrome, Congenital, 21, Presynaptic

Cellular components related to Myasthenic Syndrome, Congenital, 21, Presynaptic according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 collagen-containing extracellular matrix GO:0062023 9.43 PLG COLQ AGRN
2 cell junction GO:0030054 9.26 RAPSN DOK7 COLQ AGRN
3 neuromuscular junction GO:0031594 9.16 RAPSN COLQ
4 synapse GO:0045202 9.02 RAPSN DOK7 COLQ CHAT AGRN

Biological processes related to Myasthenic Syndrome, Congenital, 21, Presynaptic according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 neurotransmitter secretion GO:0007269 9.37 SLC18A3 CHAT
2 protein N-linked glycosylation GO:0006487 9.32 GFPT1 DPAGT1
3 neuromuscular junction development GO:0007528 9.26 DOK7 AGRN
4 dolichol-linked oligosaccharide biosynthetic process GO:0006488 9.16 DPAGT1 ALG14
5 UDP-N-acetylglucosamine metabolic process GO:0006047 8.96 GFPT1 DPAGT1
6 regulation of synaptic growth at neuromuscular junction GO:0008582 8.62 COLQ AGRN

Sources for Myasthenic Syndrome, Congenital, 21, Presynaptic

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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