MCID: MYS054
MIFTS: 35

Myasthenic Syndrome, Congenital, 9, Associated with Acetylcholine Receptor Deficiency

Categories: Genetic diseases, Neuronal diseases

Aliases & Classifications for Myasthenic Syndrome, Congenital, 9, Associated with Acetylcholine...

MalaCards integrated aliases for Myasthenic Syndrome, Congenital, 9, Associated with Acetylcholine Receptor Deficiency:

Name: Myasthenic Syndrome, Congenital, 9, Associated with Acetylcholine Receptor Deficiency 57 75 29 6
Cms9 57 12 75
Congenital Myasthenic Syndrome 9 12 15
Myasthenic Syndrome, Congenital, Type 9, Associated with Acetylcholine Receptor Deficiency 40
Congenital Myasthenic Syndrome 9, Associated with Acetylcholine Receptor Deficiency 12

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
cholinesterase inhibitors may be beneficial


HPO:

32
myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency:
Onset and clinical course infantile onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Myasthenic Syndrome, Congenital, 9, Associated with Acetylcholine...

UniProtKB/Swiss-Prot : 75 Myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency: 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. CMS9 is a disorder of postsynaptic neuromuscular transmission, due to deficiency of AChR at the endplate that results in low amplitude of the miniature endplate potential and current.

MalaCards based summary : Myasthenic Syndrome, Congenital, 9, Associated with Acetylcholine Receptor Deficiency, also known as cms9, is related to toxic encephalopathy and carbuncle. An important gene associated with Myasthenic Syndrome, Congenital, 9, Associated with Acetylcholine Receptor Deficiency is MUSK (Muscle Associated Receptor Tyrosine Kinase), and among its related pathways/superpathways are ERK Signaling and Endometrial cancer. Related phenotypes are neck muscle weakness and ptosis

Disease Ontology : 12 A congenital myasthenic syndrome characterized by autosomal recessive inheritance of defects in postsynaptic neuromuscular junctions, reduced miniature endplate potential amplitude, proximal muscle weakness and episodic respiratory insufficiency that has material basis in homozygous or compound heterozygous mutation in the MUSK gene on chromosome 9q31.

OMIM : 57 Congenital myasthenic syndrome associated with AChR deficiency is a disorder of the postsynaptic neuromuscular junction (NMJ) clinically characterized by early-onset muscle weakness with variable severity. Electrophysiologic studies show low amplitude of the miniature endplate potential (MEPP) and current (MEPC) resulting from deficiency of AChR at the endplate. Patients may show a favorable response to amifampridine (summary by Engel et al., 2015). For a discussion of genetic heterogeneity of CMS, see CMS1A (601462). (616325)

Related Diseases for Myasthenic Syndrome, Congenital, 9, Associated with Acetylcholine...

Diseases related to Myasthenic Syndrome, Congenital, 9, Associated with Acetylcholine Receptor Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 toxic encephalopathy 9.4 CYCS MAPK8
2 carbuncle 9.2 BCL2L1 CYCS MAPK8
3 cardiomyopathy, familial hypertrophic, 2 9.2 ANXA5 CYCS MAPK8
4 acute promyelocytic leukemia 9.0 ANXA5 CYCS MAPK8
5 leukemia, chronic myeloid 8.5 ABL1 ANXA5 BCL2L1 MAPK8
6 leukemia, acute myeloid 8.2 ABL1 ANXA5 BCL2L1 MAP2K7 MAPK8

Graphical network of the top 20 diseases related to Myasthenic Syndrome, Congenital, 9, Associated with Acetylcholine Receptor Deficiency:



Diseases related to Myasthenic Syndrome, Congenital, 9, Associated with Acetylcholine Receptor Deficiency

Symptoms & Phenotypes for Myasthenic Syndrome, Congenital, 9, Associated with Acetylcholine...

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
ptosis
ophthalmoplegia

Muscle Soft Tissue:
easy fatigability
hypotonia, neonatal
gower sign
muscle weakness, mainly proximal
reduced miniature endplate potential (mepp) amplitude
more
Respiratory:
respiratory insufficiency, episodic

Head And Neck Neck:
neck muscle weakness

Head And Neck Face:
facial weakness


Clinical features from OMIM:

616325

Human phenotypes related to Myasthenic Syndrome, Congenital, 9, Associated with Acetylcholine Receptor Deficiency:

32 (show all 8)
# Description HPO Frequency HPO Source Accession
1 neck muscle weakness 32 HP:0000467
2 ptosis 32 HP:0000508
3 ophthalmoplegia 32 HP:0000602
4 neonatal hypotonia 32 HP:0001319
5 respiratory insufficiency 32 HP:0002093
6 easy fatigability 32 HP:0003388
7 gowers sign 32 HP:0003391
8 facial palsy 32 HP:0010628

GenomeRNAi Phenotypes related to Myasthenic Syndrome, Congenital, 9, Associated with Acetylcholine Receptor Deficiency according to GeneCards Suite gene sharing:

26 (show all 11)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00055-A-2 9.96 MUSK
2 Decreased viability GR00173-A 9.96 MUSK
3 Decreased viability GR00221-A-1 9.96 ABL1 MAP2K7 MAPK8 MUSK
4 Decreased viability GR00221-A-2 9.96 ABL1 MAPK8
5 Decreased viability GR00221-A-3 9.96 ABL1
6 Decreased viability GR00221-A-4 9.96 MUSK
7 Decreased viability GR00342-S-1 9.96 MAP2K7 ABL1
8 Decreased viability GR00342-S-2 9.96 ABL1 MAPK8
9 Decreased viability GR00342-S-3 9.96 ABL1 MAPK8
10 Decreased viability GR00402-S-2 9.96 ABL1 MAP2K7 MAPK8 MUSK
11 Increased viability after TNF/CHX stimulation GR00228-A 8.62 MAPK8 MUSK

Drugs & Therapeutics for Myasthenic Syndrome, Congenital, 9, Associated with Acetylcholine...

Search Clinical Trials , NIH Clinical Center for Myasthenic Syndrome, Congenital, 9, Associated with Acetylcholine Receptor Deficiency

Genetic Tests for Myasthenic Syndrome, Congenital, 9, Associated with Acetylcholine...

Genetic tests related to Myasthenic Syndrome, Congenital, 9, Associated with Acetylcholine Receptor Deficiency:

# Genetic test Affiliating Genes
1 Myasthenic Syndrome, Congenital, 9, Associated with Acetylcholine Receptor Deficiency 29 MUSK

Anatomical Context for Myasthenic Syndrome, Congenital, 9, Associated with Acetylcholine...

Publications for Myasthenic Syndrome, Congenital, 9, Associated with Acetylcholine...

Variations for Myasthenic Syndrome, Congenital, 9, Associated with Acetylcholine...

UniProtKB/Swiss-Prot genetic disease variations for Myasthenic Syndrome, Congenital, 9, Associated with Acetylcholine Receptor Deficiency:

75
# Symbol AA change Variation ID SNP ID
1 MUSK p.Val790Met VAR_023046 rs199476083
2 MUSK p.Met605Ile VAR_066604 rs766640370
3 MUSK p.Ala727Val VAR_066605 rs397515450
4 MUSK p.Asp38Glu VAR_072785 rs775587809
5 MUSK p.Pro344Arg VAR_072786 rs387906803
6 MUSK p.Met835Val VAR_072788

ClinVar genetic disease variations for Myasthenic Syndrome, Congenital, 9, Associated with Acetylcholine Receptor Deficiency:

6
(show top 50) (show all 114)
# Gene Variation Type Significance SNP ID Assembly Location
1 MUSK NM_005592.3(MUSK): c.220dupC (p.Arg74Profs) duplication Pathogenic rs879255561 GRCh37 Chromosome 9, 113449410: 113449410
2 MUSK NM_005592.3(MUSK): c.220dupC (p.Arg74Profs) duplication Pathogenic rs879255561 GRCh38 Chromosome 9, 110687130: 110687130
3 MUSK NM_005592.3(MUSK): c.1031C> G (p.Pro344Arg) single nucleotide variant Pathogenic rs387906803 GRCh37 Chromosome 9, 113530210: 113530210
4 MUSK NM_005592.3(MUSK): c.1031C> G (p.Pro344Arg) single nucleotide variant Pathogenic rs387906803 GRCh38 Chromosome 9, 110767930: 110767930
5 MUSK MUSK, MET605ILE undetermined variant Pathogenic
6 MUSK NM_005592.3(MUSK): c.2180C> T (p.Ala727Val) single nucleotide variant Pathogenic rs397515450 GRCh37 Chromosome 9, 113562838: 113562838
7 MUSK NM_005592.3(MUSK): c.2180C> T (p.Ala727Val) single nucleotide variant Pathogenic rs397515450 GRCh38 Chromosome 9, 110800558: 110800558
8 MUSK NM_005592.3(MUSK): c.398T> C (p.Ile133Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs55980069 GRCh37 Chromosome 9, 113457722: 113457722
9 MUSK NM_005592.3(MUSK): c.398T> C (p.Ile133Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs55980069 GRCh38 Chromosome 9, 110695442: 110695442
10 MUSK NM_005592.3(MUSK): c.486G> C (p.Arg162Ser) single nucleotide variant Uncertain significance rs200750233 GRCh37 Chromosome 9, 113457810: 113457810
11 MUSK NM_005592.3(MUSK): c.486G> C (p.Arg162Ser) single nucleotide variant Uncertain significance rs200750233 GRCh38 Chromosome 9, 110695530: 110695530
12 MUSK NM_005592.3(MUSK): c.374G> T (p.Arg125Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs375737188 GRCh37 Chromosome 9, 113457698: 113457698
13 MUSK NM_005592.3(MUSK): c.374G> T (p.Arg125Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs375737188 GRCh38 Chromosome 9, 110695418: 110695418
14 MUSK NM_005592.3(MUSK): c.308A> G (p.Asn103Ser) single nucleotide variant Likely pathogenic rs551423795 GRCh37 Chromosome 9, 113449498: 113449498
15 MUSK NM_005592.3(MUSK): c.308A> G (p.Asn103Ser) single nucleotide variant Likely pathogenic rs551423795 GRCh38 Chromosome 9, 110687218: 110687218
16 MUSK NM_005592.3(MUSK): c.2382G> C (p.Glu794Asp) single nucleotide variant Likely pathogenic rs756877019 GRCh37 Chromosome 9, 113563040: 113563040
17 MUSK NM_005592.3(MUSK): c.2382G> C (p.Glu794Asp) single nucleotide variant Likely pathogenic rs756877019 GRCh38 Chromosome 9, 110800760: 110800760
18 MUSK NM_005592.3(MUSK): c.320G> A (p.Gly107Glu) single nucleotide variant Conflicting interpretations of pathogenicity rs55786136 GRCh38 Chromosome 9, 110687230: 110687230
19 MUSK NM_005592.3(MUSK): c.320G> A (p.Gly107Glu) single nucleotide variant Conflicting interpretations of pathogenicity rs55786136 GRCh37 Chromosome 9, 113449510: 113449510
20 MUSK NM_005592.3(MUSK): c.666T> C (p.Asn222=) single nucleotide variant Conflicting interpretations of pathogenicity rs56044404 GRCh37 Chromosome 9, 113496568: 113496568
21 MUSK NM_005592.3(MUSK): c.666T> C (p.Asn222=) single nucleotide variant Conflicting interpretations of pathogenicity rs56044404 GRCh38 Chromosome 9, 110734288: 110734288
22 MUSK NM_005592.3(MUSK): c.1189T> C (p.Tyr397His) single nucleotide variant Conflicting interpretations of pathogenicity rs79843573 GRCh38 Chromosome 9, 110775792: 110775792
23 MUSK NM_005592.3(MUSK): c.1189T> C (p.Tyr397His) single nucleotide variant Conflicting interpretations of pathogenicity rs79843573 GRCh37 Chromosome 9, 113538072: 113538072
24 MUSK NM_005592.3(MUSK): c.1719T> C (p.Asn573=) single nucleotide variant Likely benign rs373118888 GRCh37 Chromosome 9, 113547939: 113547939
25 MUSK NM_005592.3(MUSK): c.1719T> C (p.Asn573=) single nucleotide variant Likely benign rs373118888 GRCh38 Chromosome 9, 110785659: 110785659
26 MUSK NM_005592.3(MUSK): c.1931T> C (p.Val644Ala) single nucleotide variant Conflicting interpretations of pathogenicity rs41279055 GRCh37 Chromosome 9, 113562589: 113562589
27 MUSK NM_005592.3(MUSK): c.1931T> C (p.Val644Ala) single nucleotide variant Conflicting interpretations of pathogenicity rs41279055 GRCh38 Chromosome 9, 110800309: 110800309
28 MUSK NM_005592.3(MUSK): c.1991A> G (p.Asn664Ser) single nucleotide variant Benign rs55963442 GRCh37 Chromosome 9, 113562649: 113562649
29 MUSK NM_005592.3(MUSK): c.1991A> G (p.Asn664Ser) single nucleotide variant Benign rs55963442 GRCh38 Chromosome 9, 110800369: 110800369
30 MUSK NM_005592.3(MUSK): c.665A> G (p.Asn222Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs55826142 GRCh37 Chromosome 9, 113496567: 113496567
31 MUSK NM_005592.3(MUSK): c.665A> G (p.Asn222Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs55826142 GRCh38 Chromosome 9, 110734287: 110734287
32 MUSK NM_005592.3(MUSK): c.1941C> T (p.Val647=) single nucleotide variant Conflicting interpretations of pathogenicity rs200312379 GRCh37 Chromosome 9, 113562599: 113562599
33 MUSK NM_005592.3(MUSK): c.1941C> T (p.Val647=) single nucleotide variant Conflicting interpretations of pathogenicity rs200312379 GRCh38 Chromosome 9, 110800319: 110800319
34 MUSK NM_005592.3(MUSK): c.80-8C> T single nucleotide variant Conflicting interpretations of pathogenicity rs199705752 GRCh38 Chromosome 9, 110682666: 110682666
35 MUSK NM_005592.3(MUSK): c.80-8C> T single nucleotide variant Conflicting interpretations of pathogenicity rs199705752 GRCh37 Chromosome 9, 113444946: 113444946
36 MUSK NM_005592.3(MUSK): c.312T> C (p.Gly104=) single nucleotide variant Conflicting interpretations of pathogenicity rs56181115 GRCh37 Chromosome 9, 113449502: 113449502
37 MUSK NM_005592.3(MUSK): c.312T> C (p.Gly104=) single nucleotide variant Conflicting interpretations of pathogenicity rs56181115 GRCh38 Chromosome 9, 110687222: 110687222
38 MUSK NM_005592.3(MUSK): c.2286C> T (p.Asp762=) single nucleotide variant Conflicting interpretations of pathogenicity rs199832657 GRCh37 Chromosome 9, 113562944: 113562944
39 MUSK NM_005592.3(MUSK): c.2286C> T (p.Asp762=) single nucleotide variant Conflicting interpretations of pathogenicity rs199832657 GRCh38 Chromosome 9, 110800664: 110800664
40 MUSK NM_005592.3(MUSK): c.2393A> G (p.Tyr798Cys) single nucleotide variant Uncertain significance rs188840021 GRCh37 Chromosome 9, 113563051: 113563051
41 MUSK NM_005592.3(MUSK): c.2393A> G (p.Tyr798Cys) single nucleotide variant Uncertain significance rs188840021 GRCh38 Chromosome 9, 110800771: 110800771
42 MUSK NM_005592.3(MUSK): c.2573G> A (p.Arg858His) single nucleotide variant Conflicting interpretations of pathogenicity rs34115159 GRCh37 Chromosome 9, 113563231: 113563231
43 MUSK NM_005592.3(MUSK): c.2573G> A (p.Arg858His) single nucleotide variant Conflicting interpretations of pathogenicity rs34115159 GRCh38 Chromosome 9, 110800951: 110800951
44 MUSK NM_005592.3(MUSK): c.1128C> A (p.Asn376Lys) single nucleotide variant Uncertain significance rs773285595 GRCh37 Chromosome 9, 113530307: 113530307
45 MUSK NM_005592.3(MUSK): c.1128C> A (p.Asn376Lys) single nucleotide variant Uncertain significance rs773285595 GRCh38 Chromosome 9, 110768027: 110768027
46 MUSK NM_005592.3(MUSK): c.359-2dup duplication Uncertain significance GRCh37 Chromosome 9, 113457681: 113457681
47 MUSK NM_005592.3(MUSK): c.359-2dup duplication Uncertain significance GRCh38 Chromosome 9, 110695401: 110695401
48 MUSK NC_000009.12: g.(?_110734231)_(110734395_?)del deletion Pathogenic GRCh38 Chromosome 9, 110734231: 110734395
49 MUSK NM_005592.3(MUSK): c.481C> T (p.Leu161Phe) single nucleotide variant Uncertain significance GRCh37 Chromosome 9, 113457805: 113457805
50 MUSK NM_005592.3(MUSK): c.481C> T (p.Leu161Phe) single nucleotide variant Uncertain significance GRCh38 Chromosome 9, 110695525: 110695525

Expression for Myasthenic Syndrome, Congenital, 9, Associated with Acetylcholine...

Search GEO for disease gene expression data for Myasthenic Syndrome, Congenital, 9, Associated with Acetylcholine Receptor Deficiency.

Pathways for Myasthenic Syndrome, Congenital, 9, Associated with Acetylcholine...

Pathways related to Myasthenic Syndrome, Congenital, 9, Associated with Acetylcholine Receptor Deficiency according to GeneCards Suite gene sharing:

(show all 34)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.59 ABL1 BCL2L1 CYCS MAP2K7 MAPK8 MUSK
2
Show member pathways
12.58 ABL1 BCL2L1 CYCS MAPK8
3
Show member pathways
12.56 BCL2L1 CYCS MAP2K7 MAPK8
4 12.52 ABL1 BCL2L1 CYCS MAPK8
5
Show member pathways
12.49 ABL1 CYCS MAP2K7 MAPK8
6
Show member pathways
12.4 ABL1 BCL2L1 MAPK8 PLA2G2C
7
Show member pathways
12.36 BCL2L1 CYCS MAPK8
8
Show member pathways
12.35 CYCS MAP2K7 MAPK8
9
Show member pathways
12.34 BCL2L1 MAP2K7 MAPK8
10
Show member pathways
12.26 ABL1 MAP2K7 MAPK8
11
Show member pathways
12.23 BCL2L1 MAP2K7 MAPK8
12
Show member pathways
12.23 CYCS MAP2K7 MAPK8
13
Show member pathways
12.2 BCL2L1 MAP2K7 MAPK8
14
Show member pathways
12.18 ABL1 BCL2L1 CYCS MAP2K7 MAPK8
15
Show member pathways
12.14 ABL1 BCL2L1 CYCS
16
Show member pathways
12.02 ABL1 BCL2L1 MAPK8
17
Show member pathways
12.01 BCL2L1 CYCS MAPK8
18
Show member pathways
11.7 BCL2L1 CYCS MAPK8
19
Show member pathways
11.5 BCL2L1 CYCS MAPK8
20
Show member pathways
11.46 CYCS MAP2K7 MAPK8
21 11.4 MAPK8 MUSK
23 11.35 BCL2L1 MAPK8
24 11.27 CYCS MAPK8
25 11.26 MAP2K7 MAPK8
26 11.25 MAP2K7 MAPK8
27 11.14 BCL2L1 MAP2K7 MAPK8
28 11.05 MAP2K7 MAPK8
29 11.03 CYCS MAPK8
30 10.99 BCL2L1 MAPK8
31 10.91 BCL2L1 CYCS
32 10.67 ABL1 BCL2L1 CYCS MAPK8
33
Show member pathways
10.48 BCL2L1 CYCS MAP2K7 MAPK8
34 9.92 BCL2L1 CYCS

GO Terms for Myasthenic Syndrome, Congenital, 9, Associated with Acetylcholine...

Biological processes related to Myasthenic Syndrome, Congenital, 9, Associated with Acetylcholine Receptor Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 phosphorylation GO:0016310 9.67 ABL1 MAP2K7 MAPK8 MUSK
2 regulation of apoptotic process GO:0042981 9.65 ABL1 BCL2L1 MAP2K7
3 apoptotic process GO:0006915 9.62 ABL1 BCL2L1 CYCS MAP2K7
4 protein phosphorylation GO:0006468 9.56 ABL1 MAP2K7 MAPK8 MUSK
5 JNK cascade GO:0007254 9.46 MAP2K7 MAPK8
6 intrinsic apoptotic signaling pathway in response to DNA damage GO:0008630 9.43 ABL1 BCL2L1
7 response to UV GO:0009411 9.4 MAP2K7 MAPK8
8 negative regulation of apoptotic process GO:0043066 9.26 ANXA5 BCL2L1 MAPK8 MUSK
9 stress-activated MAPK cascade GO:0051403 9.16 MAP2K7 MAPK8
10 peptidyl-tyrosine phosphorylation GO:0018108 8.8 ABL1 MAP2K7 MUSK

Molecular functions related to Myasthenic Syndrome, Congenital, 9, Associated with Acetylcholine Receptor Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 kinase activity GO:0016301 9.46 ABL1 MAP2K7 MAPK8 MUSK
2 protein tyrosine kinase activity GO:0004713 9.13 ABL1 MAP2K7 MUSK
3 protein kinase activity GO:0004672 8.92 ABL1 MAP2K7 MAPK8 MUSK

Sources for Myasthenic Syndrome, Congenital, 9, Associated with Acetylcholine...

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69 SNOMED-CT via HPO
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74 UMLS via Orphanet
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