CMS8
MCID: MYS076
MIFTS: 35

Myasthenic Syndrome, Congenital, 8 (CMS8)

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

Aliases & Classifications for Myasthenic Syndrome, Congenital, 8

MalaCards integrated aliases for Myasthenic Syndrome, Congenital, 8:

Name: Myasthenic Syndrome, Congenital, 8 56 73 29 6
Myasthenic Syndrome, Congenital, 8, with Pre- and Postsynaptic Defects 56 73 29
Myasthenic Syndrome, Congenital, with Pre- and Postsynaptic Defects 56 73 71
Cms8 56 12 73
Congenital Myasthenic Syndrome Due to Agrin Deficiency 12 73
Congenital Myasthenic Syndrome 8 12 15
Cmsppd 56 73
Myasthenic Syndrome, Congenital, with Pre- and Postsynaptic Defects; Cmsppd 56
Myasthenic Syndrome, Congenital, Type 8, with Pre- and Postsynaptic Defects 39
Congenital Myasthenic Syndrome 8 with Pre- and Postsynaptic Defects 12
Myasthenic Syndrome, Congenital, Due to Agrin Deficiency 56

Characteristics:

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
variable severity
onset in early childhood
two families have been reported (last curated april 2014)


HPO:

31
myasthenic syndrome, congenital, 8:
Inheritance autosomal recessive inheritance
Onset and clinical course variable expressivity


Classifications:



External Ids:

Disease Ontology 12 DOID:0110657
OMIM 56 615120
OMIM Phenotypic Series 56 PS601462
MeSH 43 D020294
UMLS 71 C3808739

Summaries for Myasthenic Syndrome, Congenital, 8

UniProtKB/Swiss-Prot : 73 Myasthenic syndrome, congenital, 8: 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. CMS8 is an autosomal recessive disease characterized by prominent defects of both the pre- and postsynaptic regions. Affected individuals have onset of muscle weakness in early childhood; the severity of the weakness and muscles affected is variable.

MalaCards based summary : Myasthenic Syndrome, Congenital, 8, is also known as myasthenic syndrome, congenital, 8, with pre- and postsynaptic defects, and has symptoms including facial paresis An important gene associated with Myasthenic Syndrome, Congenital, 8 is AGRN (Agrin), and among its related pathways/superpathways are Degradation of the extracellular matrix and Antiarrhythmic Pathway, Pharmacodynamics. Related phenotypes are high palate and respiratory insufficiency

Disease Ontology : 12 A congenital myasthenic syndrome characterized by autosomal recessive inheritance of prominent defects of both the pre- and postsynaptic regions and muscle weakness that has material basis in homozygous or compound heterozygous mutation in the AGRN gene on chromosome 1p.

OMIM : 56 Congenital myasthenic syndromes are genetic disorders of the neuromuscular junction (NMJ) that are classified by the site of the transmission defect: presynaptic, synaptic, and postsynaptic. CMS8 is an autosomal recessive disorder characterized by prominent defects of both the pre- and postsynaptic regions. Affected individuals have onset of muscle weakness in early childhood; the severity of the weakness and muscles affected is variable (summary by Maselli et al., 2012). For a discussion of genetic heterogeneity of CMS, see CMS1A (601462). (615120)

Related Diseases for Myasthenic Syndrome, Congenital, 8

Symptoms & Phenotypes for Myasthenic Syndrome, Congenital, 8

Human phenotypes related to Myasthenic Syndrome, Congenital, 8:

31 (show all 7)
# Description HPO Frequency HPO Source Accession
1 high palate 31 occasional (7.5%) HP:0000218
2 respiratory insufficiency 31 occasional (7.5%) HP:0002093
3 ptosis 31 HP:0000508
4 easy fatigability 31 HP:0003388
5 facial palsy 31 HP:0010628
6 narrow chest 31 HP:0000774
7 proximal muscle weakness 31 HP:0003701

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Eyes:
ptosis
extraocular muscle weakness, mild (1 patient)

Chest External Features:
narrow thorax

Respiratory:
respiratory insufficiency (1 patient)

Muscle Soft Tissue:
easy fatigability
muscle weakness, proximal
inability to run
muscle weakness may affect upper limbs
type ii fiber atrophy seen on muscle biopsy
more
Head And Neck Face:
facial weakness

Head And Neck Mouth:
high-arched palate (1 patient)

Clinical features from OMIM:

615120

UMLS symptoms related to Myasthenic Syndrome, Congenital, 8:


facial paresis

GenomeRNAi Phenotypes related to Myasthenic Syndrome, Congenital, 8 according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased HPV16-GFP infection GR00350-A 8.8 KCNJ3 KCNK1 SLC7A13

Drugs & Therapeutics for Myasthenic Syndrome, Congenital, 8

Search Clinical Trials , NIH Clinical Center for Myasthenic Syndrome, Congenital, 8

Genetic Tests for Myasthenic Syndrome, Congenital, 8

Genetic tests related to Myasthenic Syndrome, Congenital, 8:

# Genetic test Affiliating Genes
1 Myasthenic Syndrome, Congenital, 8 29 AGRN
2 Myasthenic Syndrome, Congenital, 8, with Pre- and Postsynaptic Defects 29

Anatomical Context for Myasthenic Syndrome, Congenital, 8

Publications for Myasthenic Syndrome, Congenital, 8

Articles related to Myasthenic Syndrome, Congenital, 8:

# Title Authors PMID Year
1
LG2 agrin mutation causing severe congenital myasthenic syndrome mimics functional characteristics of non-neural (z-) agrin. 56 6
22205389 2012
2
Identification of an agrin mutation that causes congenital myasthenia and affects synapse function. 56 6
19631309 2009
3
Congenital Myasthenic Syndromes 6
20301347 2003
4
Distinct roles of nerve and muscle in postsynaptic differentiation of the neuromuscular synapse. 56
11323662 2001
5
Cryptic CTL epitope on a murine sarcoma Meth A generated by exon extension as a novel mechanism. 61
12707369 2003
6
Irrelevance of the mutated p53 gene product to tumor rejection antigen in 3-methylcholanthrene-induced fibrosarcomas. 61
21544462 1996

Variations for Myasthenic Syndrome, Congenital, 8

ClinVar genetic disease variations for Myasthenic Syndrome, Congenital, 8:

6 (show top 50) (show all 511) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 covers 29 genes, none of which curated to show dosage sensitivity NC_000001.11:g.(?_1020153)_(1313808_?)deldeletion Pathogenic 541215 1:955533-1249188 1:1020153-1313808
2 AGRN NM_198576.4(AGRN):c.1036_1039dup (p.Glu347fs)duplication Pathogenic 654968 1:976939-976940 1:1041559-1041560
3 AGRN NM_198576.4(AGRN):c.914_947del (p.Arg305fs)deletion Pathogenic 574478 rs1557700705 1:976735-976768 1:1041355-1041388
4 subset of 48 genes: GNB1 NC_000001.10:g.(?_955543)_(2238214_?)deldeletion Pathogenic 832780 1:955543-2238214
5 AGRN NM_198576.4(AGRN):c.1275C>G (p.Tyr425Ter)SNV Pathogenic 644955 1:977433-977433 1:1042053-1042053
6 AGRN NM_198576.4(AGRN):c.902_912del (p.Arg301fs)deletion Pathogenic 654128 1:976719-976729 1:1041339-1041349
7 AGRN NM_198576.4(AGRN):c.5125G>C (p.Gly1709Arg)SNV Pathogenic 18241 rs199476396 1:985955-985955 1:1050575-1050575
8 AGRN NM_198576.4(AGRN):c.5179G>T (p.Val1727Phe)SNV Pathogenic 126555 rs587777298 1:986143-986143 1:1050763-1050763
9 AGRN NM_198576.4(AGRN):c.1057C>T (p.Gln353Ter)SNV Pathogenic 126556 rs587777299 1:976962-976962 1:1041582-1041582
10 AGRN NM_198576.4(AGRN):c.5276T>C (p.Leu1759Pro)SNV Likely pathogenic 617537 rs1557721600 1:986655-986655 1:1051275-1051275
11 AGRN NM_198576.4(AGRN):c.4745-47_4753deldeletion Likely pathogenic 801429 1:985236-985291 1:1049856-1049911
12 AGRN NM_198576.4(AGRN):c.5353G>A (p.Asp1785Asn)SNV Conflicting interpretations of pathogenicity 128314 rs144245019 1:986732-986732 1:1051352-1051352
13 AGRN NM_198576.4(AGRN):c.67G>C (p.Val23Leu)SNV Conflicting interpretations of pathogenicity 210112 rs201073369 1:955619-955619 1:1020239-1020239
14 AGRN NM_198576.4(AGRN):c.1993G>A (p.Glu665Lys)SNV Conflicting interpretations of pathogenicity 210106 rs143324306 1:979397-979397 1:1044017-1044017
15 AGRN NM_198576.4(AGRN):c.3732C>T (p.His1244=)SNV Conflicting interpretations of pathogenicity 210108 rs536657086 1:983256-983256 1:1047876-1047876
16 AGRN NM_198576.4(AGRN):c.2690C>T (p.Ala897Val)SNV Conflicting interpretations of pathogenicity 235570 rs116836855 1:981353-981353 1:1045973-1045973
17 AGRN NM_198576.4(AGRN):c.4639G>A (p.Glu1547Lys)SNV Conflicting interpretations of pathogenicity 252808 rs2799068 1:985070-985070 1:1049690-1049690
18 AGRN NM_198576.4(AGRN):c.5201G>A (p.Arg1734His)SNV Conflicting interpretations of pathogenicity 263195 rs145444272 1:986165-986165 1:1050785-1050785
19 AGRN NM_198576.4(AGRN):c.2501G>A (p.Arg834Gln)SNV Conflicting interpretations of pathogenicity 387869 rs146243145 1:980868-980868 1:1045488-1045488
20 AGRN NM_198576.4(AGRN):c.2013C>T (p.Ser671=)SNV Conflicting interpretations of pathogenicity 501493 rs141603403 1:979502-979502 1:1044122-1044122
21 AGRN NM_198576.4(AGRN):c.752T>C (p.Val251Ala)SNV Conflicting interpretations of pathogenicity 430121 rs779170859 1:976577-976577 1:1041197-1041197
22 AGRN NM_198576.4(AGRN):c.1570C>T (p.Arg524Trp)SNV Conflicting interpretations of pathogenicity 446814 rs144164397 1:978804-978804 1:1043424-1043424
23 AGRN NM_198576.4(AGRN):c.4967G>A (p.Arg1656Gln)SNV Uncertain significance 451650 rs374905300 1:985700-985700 1:1050320-1050320
24 AGRN NM_198576.4(AGRN):c.5C>A (p.Ala2Asp)SNV Uncertain significance 474165 rs776698665 1:955557-955557 1:1020177-1020177
25 AGRN NM_198576.4(AGRN):c.5990C>T (p.Pro1997Leu)SNV Uncertain significance 430302 rs144091542 1:990213-990213 1:1054833-1054833
26 AGRN NM_198576.4(AGRN):c.5572G>A (p.Glu1858Lys)SNV Uncertain significance 397549 rs1060499677 1:987116-987116 1:1051736-1051736
27 AGRN NM_198576.4(AGRN):c.5387G>A (p.Arg1796His)SNV Uncertain significance 424015 rs774881136 1:986849-986849 1:1051469-1051469
28 AGRN NM_198576.4(AGRN):c.3387C>T (p.Pro1129=)SNV Uncertain significance 474117 rs758046832 1:982336-982336 1:1046956-1046956
29 AGRN NM_198576.4(AGRN):c.3773C>T (p.Thr1258Met)SNV Uncertain significance 474125 rs141842070 1:983413-983413 1:1048033-1048033
30 AGRN NM_198576.4(AGRN):c.593_595AGA[1] (p.Lys199del)short repeat Uncertain significance 474163 rs749209897 1:976125-976127 1:1040745-1040747
31 AGRN NM_198576.4(AGRN):c.4840G>A (p.Glu1614Lys)SNV Uncertain significance 474139 rs147259096 1:985378-985378 1:1049998-1049998
32 AGRN NM_198576.4(AGRN):c.4622G>A (p.Arg1541Gln)SNV Uncertain significance 474136 rs760702396 1:985053-985053 1:1049673-1049673
33 AGRN NM_198576.4(AGRN):c.829C>T (p.Arg277Cys)SNV Uncertain significance 474169 rs1256837701 1:976654-976654 1:1041274-1041274
34 AGRN NM_198576.4(AGRN):c.1054C>G (p.Arg352Gly)SNV Uncertain significance 474095 rs149868381 1:976959-976959 1:1041579-1041579
35 AGRN NM_198576.4(AGRN):c.4651C>T (p.His1551Tyr)SNV Uncertain significance 474137 rs771455197 1:985082-985082 1:1049702-1049702
36 AGRN NM_198576.4(AGRN):c.1130G>A (p.Arg377Gln)SNV Uncertain significance 474096 rs1553174827 1:977035-977035 1:1041655-1041655
37 AGRN NM_198576.4(AGRN):c.1145A>G (p.Gln382Arg)SNV Uncertain significance 474097 rs1553174830 1:977050-977050 1:1041670-1041670
38 AGRN NM_198576.4(AGRN):c.1539C>T (p.Cys513=)SNV Uncertain significance 474101 rs370615022 1:978773-978773 1:1043393-1043393
39 AGRN NM_198576.4(AGRN):c.5093G>A (p.Arg1698His)SNV Uncertain significance 474143 rs551658645 1:985923-985923 1:1050543-1050543
40 AGRN NM_198576.4(AGRN):c.1721A>T (p.Tyr574Phe)SNV Uncertain significance 474102 rs749074796 1:979035-979035 1:1043655-1043655
41 AGRN NM_198576.4(AGRN):c.2713C>T (p.Arg905Cys)SNV Uncertain significance 474108 rs199593375 1:981376-981376 1:1045996-1045996
42 AGRN NM_198576.4(AGRN):c.5258C>T (p.Pro1753Leu)SNV Uncertain significance 474147 rs748126752 1:986637-986637 1:1051257-1051257
43 AGRN NM_198576.4(AGRN):c.5422G>A (p.Val1808Met)SNV Uncertain significance 474151 rs1356478300 1:986884-986884 1:1051504-1051504
44 AGRN NM_198576.4(AGRN):c.2651G>A (p.Arg884His)SNV Uncertain significance 474107 rs369686860 1:981227-981227 1:1045847-1045847
45 AGRN NM_198576.4(AGRN):c.2987C>A (p.Ala996Glu)SNV Uncertain significance 474111 rs148475305 1:981852-981852 1:1046472-1046472
46 AGRN NM_198576.4(AGRN):c.3046A>G (p.Thr1016Ala)SNV Uncertain significance 474113 rs1553176512 1:981911-981911 1:1046531-1046531
47 AGRN NM_198576.4(AGRN):c.2737G>A (p.Val913Met)SNV Uncertain significance 474109 rs140120617 1:981400-981400 1:1046020-1046020
48 AGRN NM_198576.4(AGRN):c.5995C>A (p.Leu1999Met)SNV Uncertain significance 474164 rs868724036 1:990218-990218 1:1054838-1054838
49 AGRN NM_198576.4(AGRN):c.3575G>A (p.Arg1192Gln)SNV Uncertain significance 474121 rs200339732 1:983011-983011 1:1047631-1047631
50 AGRN NM_198576.4(AGRN):c.3694C>A (p.Arg1232Ser)SNV Uncertain significance 474123 rs777331097 1:983218-983218 1:1047838-1047838

UniProtKB/Swiss-Prot genetic disease variations for Myasthenic Syndrome, Congenital, 8:

73
# Symbol AA change Variation ID SNP ID
1 AGRN p.Asn105Ile VAR_068726
2 AGRN p.Gly1709Arg VAR_068742
3 AGRN p.Val1727Phe VAR_069066
4 AGRN p.Gly76Ser VAR_071367
5 AGRN p.Gly1875Arg VAR_071369

Expression for Myasthenic Syndrome, Congenital, 8

Search GEO for disease gene expression data for Myasthenic Syndrome, Congenital, 8.

Pathways for Myasthenic Syndrome, Congenital, 8

Pathways related to Myasthenic Syndrome, Congenital, 8 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.79 PLOD1 LTBP3 AGRN
2 10.37 KCNK1 KCNJ3

GO Terms for Myasthenic Syndrome, Congenital, 8

Cellular components related to Myasthenic Syndrome, Congenital, 8 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 membrane GO:0016020 9.56 SLN SLC7A13 PLOD1 KCNK1 KCNJ3 DTL
2 voltage-gated potassium channel complex GO:0008076 8.62 KCNK1 KCNJ3

Molecular functions related to Myasthenic Syndrome, Congenital, 8 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 inward rectifier potassium channel activity GO:0005242 8.62 KCNK1 KCNJ3

Sources for Myasthenic Syndrome, Congenital, 8

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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