MCID: MYS061
MIFTS: 39

Myasthenic Syndrome, Congenital, 4c, Associated with Acetylcholine Receptor Deficiency

Categories: Genetic diseases, Neuronal diseases

Aliases & Classifications for Myasthenic Syndrome, Congenital, 4c, Associated with...

MalaCards integrated aliases for Myasthenic Syndrome, Congenital, 4c, Associated with Acetylcholine Receptor Deficiency:

Name: Myasthenic Syndrome, Congenital, 4c, Associated with Acetylcholine Receptor Deficiency 57 75
Cms4c 57 12 75
Myasthenic Syndrome, Congenital, Associated with Acetylcholine Receptor Deficiency 75 73
Congenital Myasthenic Syndrome Type Id 12 75
Congenital Myasthenic Syndrome 4c 12 15
Cms Id 12 75
Cms1d 12 75
Fim1 12 75
Myasthenic Syndrome, Congenital, with Facial Dysmorphism, Associated with Acetylcholine Receptor Deficiency 29
Congenital Myasthenic Syndrome with Facial Dysmorphism Associated with Acetylcholine Receptor Deficiency 75
Congenital Myasthenic Syndrome Post-Synaptic Associated with Acetylcholine Receptor Deficiency 75
Myasthenic Syndrome, Congenital, Type 4c, Associated with Acetylcholine Receptor Deficiency 40
Congenital Myasthenic Syndrome 4c Associated with Acetylcholine Receptor Deficiency 12
Myasthenia, Familial Infantile, 1, Formerly; Fim1, Formerly 57
Myasthenic Syndrome, Congenital, Type Id; Cms1d, Formerly 57
Myasthenia, Familial Infantile, 1, Formerly 57
Myasthenic Syndrome, Congenital, Type Id 57
Congenital Myasthenic Syndrome Type 1d 75
Congenital Myasthenic Syndrome Type 1e 75
Congenital Myasthenic Syndrome Type Ie 75
Myasthenic Syndrome, Congenital, Ie 73
Myasthenia, Familial Infantile, 1 75
Familial Infantile Myasthenia 1 12
Cms Id, Formerly 57
Cms1d, Formerly 57
Fim1, Formerly 57
Cms-Achrd 75
Cms Ie 75
Cms1e 75

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
variable severity
milder cases have onset in childhood or adulthood with history of muscle weakness since infancy
because fetal chrng exhibits phenotypic rescue
favorable response to cholinesterase inhibitors
gypsy groups demonstrate a founder effect (1267delg, )


HPO:

32
myasthenic syndrome, congenital, 4c, associated with acetylcholine receptor deficiency:
Onset and clinical course variable expressivity infantile onset nonprogressive
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Myasthenic Syndrome, Congenital, 4c, Associated with...

UniProtKB/Swiss-Prot : 75 Myasthenic syndrome, congenital, 4C, 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. CMS4C is an autosomal recessive 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, 4c, Associated with Acetylcholine Receptor Deficiency, also known as cms4c, is related to congenital myasthenic syndrome associated with acetylcholine receptor deficiency and myasthenic syndrome, congenital, 4a, slow-channel, and has symptoms including muscle cramp, facial paresis and ophthalmoparesis. An important gene associated with Myasthenic Syndrome, Congenital, 4c, Associated with Acetylcholine Receptor Deficiency is CHRNE (Cholinergic Receptor Nicotinic Epsilon Subunit), and among its related pathways/superpathways are ECM proteoglycans and Differentiation Pathway. Affiliated tissues include tongue and skeletal muscle, and related phenotypes are high palate and ptosis

Disease Ontology : 12 A congenital myasthenic syndrome characterized by autosomal recessive inheritance of postsynaptic neuromuscular junction defects, early-onset muscle weakness, and low amplitude of the miniature endplate potential and current that has material basis in homozygous or compound heterozygous mutation in the CHRNE gene on chromosome 17p13.

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 with mutations in the CHRNE gene may have compensatory increased expression of the fetal subunit CHRNG (100730) and may respond to treatment with cholinergic agents, pyridostigmine, or amifampridine (summary by Engel et al., 2015). For a discussion of genetic heterogeneity of CMS, see CMS1A (601462). (608931)

Related Diseases for Myasthenic Syndrome, Congenital, 4c, Associated with...

Graphical network of the top 20 diseases related to Myasthenic Syndrome, Congenital, 4c, Associated with Acetylcholine Receptor Deficiency:



Diseases related to Myasthenic Syndrome, Congenital, 4c, Associated with Acetylcholine Receptor Deficiency

Symptoms & Phenotypes for Myasthenic Syndrome, Congenital, 4c, Associated with...

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
ptosis
ophthalmoparesis

Abdomen Gastrointestinal:
dysphagia
poor feeding

Muscle Soft Tissue:
muscle cramps
easy fatigability
gowers sign
hypotonia
muscle atrophy
more
Head And Neck Mouth:
malocclusion
high-arched palate
tongue weakness

Skeletal:
arthrogryposis multiplex in severe cases

Voice:
dysarthria
weak cry

Respiratory:
respiratory insufficiency due to muscle weakness

Head And Neck Face:
long face
facial muscle weakness

Prenatal Manifestations Movement:
decreased fetal movements (in some patients)

Neurologic:
delayed motor development due to muscle weakness


Clinical features from OMIM:

608931

Human phenotypes related to Myasthenic Syndrome, Congenital, 4c, Associated with Acetylcholine Receptor Deficiency:

32 (show all 27)
# Description HPO Frequency HPO Source Accession
1 high palate 32 HP:0000218
2 ptosis 32 HP:0000508
3 dysarthria 32 HP:0001260
4 dysphagia 32 HP:0002015
5 facial palsy 32 HP:0010628
6 mandibular prognathia 32 HP:0000303
7 dental malocclusion 32 HP:0000689
8 decreased muscle mass 32 HP:0003199
9 respiratory insufficiency due to muscle weakness 32 HP:0002747
10 skeletal muscle atrophy 32 HP:0003202
11 feeding difficulties 32 HP:0011968
12 strabismus 32 HP:0000486
13 ophthalmoparesis 32 HP:0000597
14 arthrogryposis multiplex congenita 32 HP:0002804
15 muscle cramps 32 HP:0003394
16 abnormality of the immune system 32 HP:0002715
17 long face 32 HP:0000276
18 decreased fetal movement 32 HP:0001558
19 motor delay 32 HP:0001270
20 weak cry 32 HP:0001612
21 fatigable weakness 32 HP:0003473
22 generalized hypotonia 32 HP:0001290
23 type 2 muscle fiber atrophy 32 HP:0003554
24 easy fatigability 32 HP:0003388
25 gowers sign 32 HP:0003391
26 emg 32 HP:0003403
27 decreased size of nerve terminals 32 HP:0003443

UMLS symptoms related to Myasthenic Syndrome, Congenital, 4c, Associated with Acetylcholine Receptor Deficiency:


muscle cramp, facial paresis, ophthalmoparesis

MGI Mouse Phenotypes related to Myasthenic Syndrome, Congenital, 4c, Associated with Acetylcholine Receptor Deficiency:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.8 CHRNE CSF1R DOK7 INHBA LAMB1 MUSK
2 growth/size/body region MP:0005378 9.7 CSF1R DHFR DOK7 INHBA MUSK MYB
3 mortality/aging MP:0010768 9.61 CHRNE CSF1R DHFR DOK7 INHBA LAMB1
4 muscle MP:0005369 9.1 CHRNE DHFR DOK7 INHBA LAMB1 MUSK

Drugs & Therapeutics for Myasthenic Syndrome, Congenital, 4c, Associated with...

Search Clinical Trials , NIH Clinical Center for Myasthenic Syndrome, Congenital, 4c, Associated with Acetylcholine Receptor Deficiency

Genetic Tests for Myasthenic Syndrome, Congenital, 4c, Associated with...

Genetic tests related to Myasthenic Syndrome, Congenital, 4c, Associated with Acetylcholine Receptor Deficiency:

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

Anatomical Context for Myasthenic Syndrome, Congenital, 4c, Associated with...

MalaCards organs/tissues related to Myasthenic Syndrome, Congenital, 4c, Associated with Acetylcholine Receptor Deficiency:

41
Tongue, Skeletal Muscle

Publications for Myasthenic Syndrome, Congenital, 4c, Associated with...

Variations for Myasthenic Syndrome, Congenital, 4c, Associated with...

UniProtKB/Swiss-Prot genetic disease variations for Myasthenic Syndrome, Congenital, 4c, Associated with Acetylcholine Receptor Deficiency:

75
# Symbol AA change Variation ID SNP ID
1 CHRNE p.Arg167Leu VAR_000290 rs121909514
2 CHRNE p.Pro265Leu VAR_000291 rs759226183
3 CHRNE p.Arg331Trp VAR_000294 rs121909515

ClinVar genetic disease variations for Myasthenic Syndrome, Congenital, 4c, Associated with Acetylcholine Receptor Deficiency:

6
(show all 48)
# Gene Variation Type Significance SNP ID Assembly Location
1 DOK7 NM_173660.4(DOK7): c.1124_1127dupTGCC (p.Ala378Serfs) duplication Pathogenic rs606231128 GRCh38 Chromosome 4, 3493110: 3493113
2 DOK7 NM_173660.4(DOK7): c.1124_1127dupTGCC (p.Ala378Serfs) duplication Pathogenic rs606231128 GRCh37 Chromosome 4, 3494837: 3494840
3 RAPSN NM_005055.4(RAPSN): c.848T> C (p.Leu283Pro) single nucleotide variant Likely pathogenic rs104894293 GRCh37 Chromosome 11, 47463227: 47463227
4 RAPSN NM_005055.4(RAPSN): c.848T> C (p.Leu283Pro) single nucleotide variant Likely pathogenic rs104894293 GRCh38 Chromosome 11, 47441675: 47441675
5 CHRNE NM_000080.3(CHRNE): c.500G> T (p.Arg167Leu) single nucleotide variant Pathogenic rs121909514 GRCh37 Chromosome 17, 4805227: 4805227
6 CHRNE NM_000080.3(CHRNE): c.500G> T (p.Arg167Leu) single nucleotide variant Pathogenic rs121909514 GRCh38 Chromosome 17, 4901932: 4901932
7 CHRNE NM_000080.3(CHRNE): c.250C> T (p.Arg84Ter) single nucleotide variant Pathogenic rs121909513 GRCh37 Chromosome 17, 4805606: 4805606
8 CHRNE NM_000080.3(CHRNE): c.250C> T (p.Arg84Ter) single nucleotide variant Pathogenic rs121909513 GRCh38 Chromosome 17, 4902311: 4902311
9 CHRNE NM_000080.3(CHRNE): c.971delT (p.Ile324Thrfs) deletion Pathogenic rs879255562 GRCh38 Chromosome 17, 4899529: 4899529
10 CHRNE NM_000080.3(CHRNE): c.971delT (p.Ile324Thrfs) deletion Pathogenic rs879255562 GRCh37 Chromosome 17, 4802824: 4802824
11 CHRNE NM_000080.3(CHRNE): c.344+1G> A single nucleotide variant Pathogenic rs879253722 GRCh38 Chromosome 17, 4902216: 4902216
12 CHRNE NM_000080.3(CHRNE): c.344+1G> A single nucleotide variant Pathogenic rs879253722 GRCh37 Chromosome 17, 4805511: 4805511
13 CHRNE NM_000080.3(CHRNE): c.1030delC (p.His344Thrfs) deletion Pathogenic rs879253723 GRCh37 Chromosome 17, 4802765: 4802765
14 CHRNE NM_000080.3(CHRNE): c.1030delC (p.His344Thrfs) deletion Pathogenic rs879253723 GRCh38 Chromosome 17, 4899470: 4899470
15 CHRNE NM_000080.3(CHRNE): c.-96C> T single nucleotide variant Pathogenic rs748144899 GRCh37 Chromosome 17, 4806454: 4806454
16 CHRNE NM_000080.3(CHRNE): c.-96C> T single nucleotide variant Pathogenic rs748144899 GRCh38 Chromosome 17, 4903159: 4903159
17 CHRNE NM_000080.3(CHRNE): c.1161_1162insT (p.Lys388Terfs) insertion Pathogenic rs886037628 GRCh37 Chromosome 17, 4802550: 4802551
18 CHRNE NM_000080.3(CHRNE): c.1161_1162insT (p.Lys388Terfs) insertion Pathogenic rs886037628 GRCh38 Chromosome 17, 4899255: 4899256
19 CHRNE NM_000080.3(CHRNE): c.614_620delGGGCCAT (p.Trp205Serfs) deletion Pathogenic rs753828284 GRCh38 Chromosome 17, 4901172: 4901178
20 CHRNE NM_000080.3(CHRNE): c.614_620delGGGCCAT (p.Trp205Serfs) deletion Pathogenic rs753828284 GRCh37 Chromosome 17, 4804467: 4804473
21 CHRNE NM_000080.3(CHRNE): c.991C> T (p.Arg331Trp) single nucleotide variant Pathogenic rs121909515 GRCh37 Chromosome 17, 4802804: 4802804
22 CHRNE NM_000080.3(CHRNE): c.991C> T (p.Arg331Trp) single nucleotide variant Pathogenic rs121909515 GRCh38 Chromosome 17, 4899509: 4899509
23 CHRNE NM_000080.3(CHRNE): c.501-16G> A single nucleotide variant Pathogenic rs879255563 GRCh37 Chromosome 17, 4804936: 4804936
24 CHRNE NM_000080.3(CHRNE): c.501-16G> A single nucleotide variant Pathogenic rs879255563 GRCh38 Chromosome 17, 4901641: 4901641
25 CHRNE NM_000080.3(CHRNE): c.1033-2A> T single nucleotide variant Pathogenic rs786204773 GRCh37 Chromosome 17, 4802681: 4802681
26 CHRNE NM_000080.3(CHRNE): c.1033-2A> T single nucleotide variant Pathogenic rs786204773 GRCh38 Chromosome 17, 4899386: 4899386
27 RAPSN NM_005055.4(RAPSN): c.737C> T (p.Ala246Val) single nucleotide variant Likely pathogenic rs559933584 GRCh37 Chromosome 11, 47463427: 47463427
28 RAPSN NM_005055.4(RAPSN): c.737C> T (p.Ala246Val) single nucleotide variant Likely pathogenic rs559933584 GRCh38 Chromosome 11, 47441875: 47441875
29 MUSK NM_005592.3(MUSK): c.79+2T> G single nucleotide variant Pathogenic rs200783529 GRCh37 Chromosome 9, 113431265: 113431265
30 MUSK NM_005592.3(MUSK): c.79+2T> G single nucleotide variant Pathogenic rs200783529 GRCh38 Chromosome 9, 110668985: 110668985
31 MUSK NM_005592.3(MUSK): c.374G> T (p.Arg125Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs375737188 GRCh37 Chromosome 9, 113457698: 113457698
32 MUSK NM_005592.3(MUSK): c.374G> T (p.Arg125Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs375737188 GRCh38 Chromosome 9, 110695418: 110695418
33 RAPSN NM_005055.4(RAPSN): c.829A> G (p.Thr277Ala) single nucleotide variant no interpretation for the single variant rs863224911 GRCh38 Chromosome 11, 47441694: 47441694
34 RAPSN NM_005055.4(RAPSN): c.829A> G (p.Thr277Ala) single nucleotide variant no interpretation for the single variant rs863224911 GRCh37 Chromosome 11, 47463246: 47463246
35 RAPSN NM_005055.4(RAPSN): c.524A> G (p.Gln175Arg) single nucleotide variant no interpretation for the single variant rs863224912 GRCh37 Chromosome 11, 47469371: 47469371
36 RAPSN NM_005055.4(RAPSN): c.524A> G (p.Gln175Arg) single nucleotide variant no interpretation for the single variant rs863224912 GRCh38 Chromosome 11, 47447819: 47447819
37 CHRNE NM_000080.3(CHRNE): c.1353dupG (p.Asn452GlufsTer4) duplication Pathogenic rs773526895 GRCh38 Chromosome 17, 4898865: 4898865
38 CHRNE NM_000080.3(CHRNE): c.1353dupG (p.Asn452GlufsTer4) duplication Pathogenic rs773526895 GRCh37 Chromosome 17, 4802160: 4802160
39 CHRNE NM_000080.3(CHRNE): c.1327delG (p.Glu443LysfsTer64) deletion Pathogenic rs763258280 GRCh37 Chromosome 17, 4802186: 4802186
40 CHRNE NM_000080.3(CHRNE): c.1327delG (p.Glu443LysfsTer64) deletion Pathogenic rs763258280 GRCh38 Chromosome 17, 4898891: 4898891
41 CHAT NM_020549.4(CHAT): c.406G> A (p.Val136Met) single nucleotide variant Conflicting interpretations of pathogenicity rs201479289 GRCh37 Chromosome 10, 50827789: 50827789
42 CHAT NM_020549.4(CHAT): c.406G> A (p.Val136Met) single nucleotide variant Conflicting interpretations of pathogenicity rs201479289 GRCh38 Chromosome 10, 49619743: 49619743
43 CHRNE NM_000080.3(CHRNE): c.1093delG (p.Ala365Profs) deletion Pathogenic rs886043239 GRCh37 Chromosome 17, 4802619: 4802619
44 CHRNE NM_000080.3(CHRNE): c.1093delG (p.Ala365Profs) deletion Pathogenic rs886043239 GRCh38 Chromosome 17, 4899324: 4899324
45 CHRNE NM_000080.3(CHRNE): c.1326+1G> A single nucleotide variant Likely pathogenic GRCh37 Chromosome 17, 4802295: 4802295
46 CHRNE NM_000080.3(CHRNE): c.1326+1G> A single nucleotide variant Likely pathogenic GRCh38 Chromosome 17, 4899000: 4899000
47 CHRNB1 NM_000747.2(CHRNB1): c.167T> C (p.Val56Ala) single nucleotide variant Uncertain significance rs759668768 GRCh38 Chromosome 17, 7445378: 7445378
48 CHRNB1 NM_000747.2(CHRNB1): c.167T> C (p.Val56Ala) single nucleotide variant Uncertain significance rs759668768 GRCh37 Chromosome 17, 7348697: 7348697

Expression for Myasthenic Syndrome, Congenital, 4c, Associated with...

Search GEO for disease gene expression data for Myasthenic Syndrome, Congenital, 4c, Associated with Acetylcholine Receptor Deficiency.

Pathways for Myasthenic Syndrome, Congenital, 4c, Associated with...

Pathways related to Myasthenic Syndrome, Congenital, 4c, Associated with Acetylcholine Receptor Deficiency according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.71 LAMB1 MUSK
2 10.3 CSF1R INHBA

GO Terms for Myasthenic Syndrome, Congenital, 4c, Associated with...

Cellular components related to Myasthenic Syndrome, Congenital, 4c, Associated with Acetylcholine Receptor Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cell junction GO:0030054 9.26 CHRNE DOK7 MUSK RIMS1
2 synapse GO:0045202 8.92 CHRNE DOK7 MUSK RIMS1

Biological processes related to Myasthenic Syndrome, Congenital, 4c, Associated with Acetylcholine Receptor Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 positive regulation of kinase activity GO:0033674 9.32 CSF1R MUSK
2 odontogenesis GO:0042476 9.26 INHBA LAMB1
3 positive regulation of protein tyrosine kinase activity GO:0061098 9.16 CSF1R DOK7
4 cell differentiation GO:0030154 9.02 CSF1R INHBA MUSK MYB RIMS1
5 endodermal cell differentiation GO:0035987 8.96 INHBA LAMB1

Molecular functions related to Myasthenic Syndrome, Congenital, 4c, Associated with Acetylcholine Receptor Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitogen-activated protein kinase kinase binding GO:0031434 8.96 CSF1R MUSK
2 transmembrane receptor protein tyrosine kinase activity GO:0004714 8.62 CSF1R MUSK

Sources for Myasthenic Syndrome, Congenital, 4c, Associated with...

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 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 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
Content
Loading form....