CMS9
MCID: MYS054
MIFTS: 29

Myasthenic Syndrome, Congenital, 9, Associated with Acetylcholine Receptor Deficiency (CMS9)

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 56 73 29 6
Cms9 56 12 73
Congenital Myasthenic Syndrome 9 12 15
Myasthenic Syndrome, Congenital, Type 9, Associated with Acetylcholine Receptor Deficiency 39
Congenital Myasthenic Syndrome 9, Associated with Acetylcholine Receptor Deficiency 12

Characteristics:

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
cholinesterase inhibitors may be beneficial


HPO:

31
myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset


Classifications:



External Ids:

Disease Ontology 12 DOID:0110670
OMIM 56 616325
OMIM Phenotypic Series 56 PS601462
MeSH 43 D020294

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

UniProtKB/Swiss-Prot : 73 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 fetal akinesia deformation sequence 1. An important gene associated with Myasthenic Syndrome, Congenital, 9, Associated with Acetylcholine Receptor Deficiency is MUSK (Muscle Associated Receptor Tyrosine Kinase). Related phenotypes are neonatal hypotonia 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 : 56 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 fetal akinesia deformation sequence 1 9.6 PLA2G1B MUSK

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

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

31 (show all 8)
# Description HPO Frequency HPO Source Accession
1 neonatal hypotonia 31 HP:0001319
2 ptosis 31 HP:0000508
3 respiratory insufficiency 31 HP:0002093
4 easy fatigability 31 HP:0003388
5 ophthalmoplegia 31 HP:0000602
6 facial palsy 31 HP:0010628
7 neck muscle weakness 31 HP:0000467
8 gowers sign 31 HP:0003391

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Eyes:
ptosis
ophthalmoplegia

Head And Neck Neck:
neck muscle weakness

Respiratory:
respiratory insufficiency, episodic

Muscle Soft Tissue:
easy fatigability
gowers sign
hypotonia, neonatal
muscle weakness, mainly proximal
reduced miniature endplate potential (mepp) amplitude
more
Head And Neck Face:
facial weakness

Clinical features from OMIM:

616325

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...

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

# Title Authors PMID Year
1
Mutations in MUSK causing congenital myasthenic syndrome impair MuSK-Dok-7 interaction. 6 56
20371544 2010
2
Refinement of the clinical phenotype in musk-related congenital myasthenic syndromes. 56 6
19949040 2009
3
MUSK, a new target for mutations causing congenital myasthenic syndrome. 56 6
15496425 2004
4
Congenital myasthenic syndromes: pathogenesis, diagnosis, and treatment. 56
25792100 2015
5
Congenital Myasthenic Syndromes 6
20301347 2003
6
Isolated vocal cord paralysis in two siblings with compound heterozygous variants in MUSK: Expanding the phenotypic spectrum. 61
30719842 2019
7
Irrelevance of the mutated p53 gene product to tumor rejection antigen in 3-methylcholanthrene-induced fibrosarcomas. 61
21544462 1996

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

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

6 (show top 50) (show all 166) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 MUSK NC_000009.12:g.(?_110734231)_(110734395_?)deldeletion Pathogenic 476127 9:110734231-110734395
2 MUSK NC_000009.12:g.(?_110668885)_(110801008_?)deldeletion Pathogenic 583579 9:113431165-113563288 9:110668885-110801008
3 MUSK NM_005592.4(MUSK):c.496C>T (p.Arg166Ter)SNV Pathogenic 849716 9:113459614-113459614 9:110697334-110697334
4 MUSK NM_005592.4(MUSK):c.220dup (p.Arg74fs)duplication Pathogenic 8240 rs879255561 9:113449407-113449408 9:110687127-110687128
5 MUSK NM_005592.4(MUSK):c.1031C>G (p.Pro344Arg)SNV Pathogenic 30175 rs387906803 9:113530210-113530210 9:110767930-110767930
6 MUSK NM_005592.4(MUSK):c.1815G>A (p.Met605Ile)SNV Pathogenic 60521 rs766640370 9:113550006-113550006 9:110787726-110787726
7 MUSK NM_005592.4(MUSK):c.2180C>T (p.Ala727Val)SNV Pathogenic 60522 rs397515450 9:113562838-113562838 9:110800558-110800558
8 MUSK NM_005592.4(MUSK):c.79+2T>GSNV Pathogenic 211542 rs200783529 9:113431265-113431265 9:110668985-110668985
9 MUSK NM_005592.4(MUSK):c.308A>G (p.Asn103Ser)SNV Likely pathogenic 218372 rs551423795 9:113449498-113449498 9:110687218-110687218
10 MUSK NM_005592.4(MUSK):c.2382G>C (p.Glu794Asp)SNV Likely pathogenic 218373 rs756877019 9:113563040-113563040 9:110800760-110800760
11 MUSK NC_000009.11:g.(?_113457663)_(113524508_?)dupduplication Likely pathogenic 583532 9:113457663-113524508 9:110695383-110762228
12 MUSK NM_005592.4(MUSK):c.486+1G>CSNV Likely pathogenic 657565 9:113457811-113457811 9:110695531-110695531
13 MUSK NM_005592.4(MUSK):c.754-2A>GSNV Likely pathogenic 664968 9:113509919-113509919 9:110747639-110747639
14 MUSK NM_005592.4(MUSK):c.549A>G (p.Glu183=)SNV Conflicting interpretations of pathogenicity 702804 9:113459667-113459667 9:110697387-110697387
15 MUSK NM_005592.4(MUSK):c.1683G>A (p.Leu561=)SNV Conflicting interpretations of pathogenicity 706306 9:113547903-113547903 9:110785623-110785623
16 MUSK NM_005592.4(MUSK):c.2291T>C (p.Ile764Thr)SNV Conflicting interpretations of pathogenicity 432075 rs1554757211 9:113562949-113562949 9:110800669-110800669
17 MUSK NM_005592.4(MUSK):c.1779-7C>TSNV Conflicting interpretations of pathogenicity 476134 rs114362384 9:113549963-113549963 9:110787683-110787683
18 MUSK NM_005592.4(MUSK):c.1863G>A (p.Ala621=)SNV Conflicting interpretations of pathogenicity 476136 rs368049319 9:113550054-113550054 9:110787774-110787774
19 MUSK NM_005592.4(MUSK):c.300G>A (p.Thr100=)SNV Conflicting interpretations of pathogenicity 476145 rs180928221 9:113449490-113449490 9:110687210-110687210
20 MUSK NM_005592.4(MUSK):c.666T>C (p.Asn222=)SNV Conflicting interpretations of pathogenicity 259812 rs56044404 9:113496568-113496568 9:110734288-110734288
21 MUSK NM_005592.4(MUSK):c.665A>G (p.Asn222Ser)SNV Conflicting interpretations of pathogenicity 281408 rs55826142 9:113496567-113496567 9:110734287-110734287
22 MUSK NM_005592.4(MUSK):c.1941C>T (p.Val647=)SNV Conflicting interpretations of pathogenicity 286073 rs200312379 9:113562599-113562599 9:110800319-110800319
23 MUSK NM_005592.4(MUSK):c.374G>T (p.Arg125Leu)SNV Conflicting interpretations of pathogenicity 211541 rs375737188 9:113457698-113457698 9:110695418-110695418
24 MUSK NM_005592.4(MUSK):c.486G>C (p.Arg162Ser)SNV Conflicting interpretations of pathogenicity 197258 rs200750233 9:113457810-113457810 9:110695530-110695530
25 MUSK NM_005592.4(MUSK):c.2368G>A (p.Val790Met)SNV Conflicting interpretations of pathogenicity 8239 rs199476083 9:113563026-113563026 9:110800746-110800746
26 MUSK NM_005592.4(MUSK):c.398T>C (p.Ile133Thr)SNV Conflicting interpretations of pathogenicity 197256 rs55980069 9:113457722-113457722 9:110695442-110695442
27 MUSK NM_005592.4(MUSK):c.1927+9dupduplication Conflicting interpretations of pathogenicity 364611 rs555725730 9:113550123-113550124 9:110787843-110787844
28 MUSK NM_005592.4(MUSK):c.1719T>C (p.Asn573=)SNV Conflicting interpretations of pathogenicity 259802 rs373118888 9:113547939-113547939 9:110785659-110785659
29 MUSK NM_005592.4(MUSK):c.1931T>C (p.Val644Ala)SNV Conflicting interpretations of pathogenicity 259805 rs41279055 9:113562589-113562589 9:110800309-110800309
30 MUSK NM_005592.4(MUSK):c.312T>C (p.Gly104=)SNV Conflicting interpretations of pathogenicity 364601 rs56181115 9:113449502-113449502 9:110687222-110687222
31 MUSK NM_005592.4(MUSK):c.206+10C>TSNV Conflicting interpretations of pathogenicity 364598 rs371617202 9:113445090-113445090 9:110682810-110682810
32 MUSK NM_005592.4(MUSK):c.233G>A (p.Arg78Gln)SNV Uncertain significance 364599 rs776815006 9:113449423-113449423 9:110687143-110687143
33 MUSK NM_005592.4(MUSK):c.239A>G (p.Asn80Ser)SNV Uncertain significance 364600 rs772926677 9:113449429-113449429 9:110687149-110687149
34 MUSK NM_005592.4(MUSK):c.857A>G (p.Asn286Ser)SNV Uncertain significance 364604 rs747154421 9:113510024-113510024 9:110747744-110747744
35 MUSK NM_005592.4(MUSK):c.1099C>T (p.Arg367Trp)SNV Uncertain significance 364605 rs201014623 9:113530278-113530278 9:110767998-110767998
36 MUSK NM_005592.4(MUSK):c.1102C>T (p.Pro368Ser)SNV Uncertain significance 364606 rs768323977 9:113530281-113530281 9:110768001-110768001
37 MUSK NM_005592.4(MUSK):c.1522G>A (p.Val508Met)SNV Uncertain significance 364610 rs769267043 9:113547232-113547232 9:110784952-110784952
38 MUSK NM_005592.4(MUSK):c.2300G>A (p.Arg767His)SNV Uncertain significance 372415 rs370079610 9:113562958-113562958 9:110800678-110800678
39 MUSK NM_005592.4(MUSK):c.1250C>T (p.Thr417Ile)SNV Uncertain significance 364607 rs538655454 9:113538133-113538133 9:110775853-110775853
40 MUSK NM_005592.4(MUSK):c.2393A>G (p.Tyr798Cys)SNV Uncertain significance 364616 rs188840021 9:113563051-113563051 9:110800771-110800771
41 MUSK NM_005592.4(MUSK):c.1291G>A (p.Val431Met)SNV Uncertain significance 364608 rs372013406 9:113538174-113538174 9:110775894-110775894
42 MUSK NM_005592.4(MUSK):c.-43G>ASNV Uncertain significance 364596 rs116884176 9:113431142-113431142 9:110668862-110668862
43 MUSK NM_005592.4(MUSK):c.780T>C (p.Ser260=)SNV Uncertain significance 364603 rs886063353 9:113509947-113509947 9:110747667-110747667
44 MUSK NM_005592.4(MUSK):c.1516A>G (p.Ile506Val)SNV Uncertain significance 364609 rs191581729 9:113547226-113547226 9:110784946-110784946
45 MUSK NM_005592.4(MUSK):c.1928-6T>CSNV Uncertain significance 364612 rs886063355 9:113562580-113562580 9:110800300-110800300
46 MUSK NM_005592.4(MUSK):c.2098G>A (p.Ala700Thr)SNV Uncertain significance 364613 rs547450130 9:113562756-113562756 9:110800476-110800476
47 MUSK NM_005592.4(MUSK):c.17A>G (p.Asn6Ser)SNV Uncertain significance 849169 9:113431201-113431201 9:110668921-110668921
48 MUSK NM_005592.4(MUSK):c.929A>C (p.Gln310Pro)SNV Uncertain significance 199112 rs201804790 9:113530108-113530108 9:110767828-110767828
49 MUSK NM_005592.4(MUSK):c.546G>C (p.Lys182Asn)SNV Uncertain significance 846586 9:113459664-113459664 9:110697384-110697384
50 MUSK NM_005592.4(MUSK):c.589G>A (p.Gly197Arg)SNV Uncertain significance 856955 9:113459707-113459707 9:110697427-110697427

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

73
# 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

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...

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

Cellular components 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 postsynaptic membrane GO:0045211 8.62 MUSK HTR3B

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 cell differentiation GO:0030154 8.8 MUSK JMJD6 CREM

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

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