MCID: MYS076
MIFTS: 23

Myasthenic Syndrome, Congenital, 8

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

Aliases & Classifications for Myasthenic Syndrome, Congenital, 8

MalaCards integrated aliases for Myasthenic Syndrome, Congenital, 8:

Name: Myasthenic Syndrome, Congenital, 8 57 75 29 6
Myasthenic Syndrome, Congenital, with Pre- and Postsynaptic Defects 57 75 73
Cms8 57 12 75
Myasthenic Syndrome, Congenital, 8, with Pre- and Postsynaptic Defects 57 75
Congenital Myasthenic Syndrome Due to Agrin Deficiency 12 75
Congenital Myasthenic Syndrome 8 12 15
Cmsppd 57 75
Myasthenic Syndrome, Congenital, with Pre- and Postsynaptic Defects; Cmsppd 57
Myasthenic Syndrome, Congenital, Type 8, with Pre- and Postsynaptic Defects 40
Congenital Myasthenic Syndrome 8 with Pre- and Postsynaptic Defects 12
Myasthenic Syndrome, Congenital, Due to Agrin Deficiency 57

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

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


HPO:

32
myasthenic syndrome, congenital, 8:
Onset and clinical course variable expressivity
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Myasthenic Syndrome, Congenital, 8

UniProtKB/Swiss-Prot : 75 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, with pre- and postsynaptic defects, and has symptoms including facial paresis An important gene associated with Myasthenic Syndrome, Congenital, 8 is AGRN (Agrin). Related phenotypes are high palate and ptosis

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 : 57 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

Symptoms via clinical synopsis from OMIM:

57
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

Human phenotypes related to Myasthenic Syndrome, Congenital, 8:

32 (show all 7)
# Description HPO Frequency HPO Source Accession
1 high palate 32 occasional (7.5%) HP:0000218
2 ptosis 32 HP:0000508
3 narrow chest 32 HP:0000774
4 respiratory insufficiency 32 occasional (7.5%) HP:0002093
5 easy fatigability 32 HP:0003388
6 proximal muscle weakness 32 HP:0003701
7 facial palsy 32 HP:0010628

UMLS symptoms related to Myasthenic Syndrome, Congenital, 8:


facial paresis

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

Anatomical Context for Myasthenic Syndrome, Congenital, 8

Publications for Myasthenic Syndrome, Congenital, 8

Variations for Myasthenic Syndrome, Congenital, 8

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

75
# 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

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

6
(show top 50) (show all 376)
# Gene Variation Type Significance SNP ID Assembly Location
1 AGRN NM_198576.3(AGRN): c.5125G> C (p.Gly1709Arg) single nucleotide variant Pathogenic rs199476396 GRCh37 Chromosome 1, 985955: 985955
2 AGRN NM_198576.3(AGRN): c.5125G> C (p.Gly1709Arg) single nucleotide variant Pathogenic rs199476396 GRCh38 Chromosome 1, 1050575: 1050575
3 AGRN NM_198576.3(AGRN): c.5179G> T (p.Val1727Phe) single nucleotide variant Pathogenic rs587777298 GRCh37 Chromosome 1, 986143: 986143
4 AGRN NM_198576.3(AGRN): c.5179G> T (p.Val1727Phe) single nucleotide variant Pathogenic rs587777298 GRCh38 Chromosome 1, 1050763: 1050763
5 AGRN NM_198576.3(AGRN): c.1057C> T (p.Gln353Ter) single nucleotide variant Pathogenic rs587777299 GRCh37 Chromosome 1, 976962: 976962
6 AGRN NM_198576.3(AGRN): c.1057C> T (p.Gln353Ter) single nucleotide variant Pathogenic rs587777299 GRCh38 Chromosome 1, 1041582: 1041582
7 AGRN NM_198576.3(AGRN): c.2457G> C (p.Gly819=) single nucleotide variant Benign/Likely benign rs112039851 GRCh38 Chromosome 1, 1045444: 1045444
8 AGRN NM_198576.3(AGRN): c.2457G> C (p.Gly819=) single nucleotide variant Benign/Likely benign rs112039851 GRCh37 Chromosome 1, 980824: 980824
9 AGRN NM_198576.3(AGRN): c.67G> C (p.Val23Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs201073369 GRCh37 Chromosome 1, 955619: 955619
10 AGRN NM_198576.3(AGRN): c.67G> C (p.Val23Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs201073369 GRCh38 Chromosome 1, 1020239: 1020239
11 AGRN NM_198576.3(AGRN): c.1993G> A (p.Glu665Lys) single nucleotide variant Benign rs143324306 GRCh37 Chromosome 1, 979397: 979397
12 AGRN NM_198576.3(AGRN): c.1993G> A (p.Glu665Lys) single nucleotide variant Benign rs143324306 GRCh38 Chromosome 1, 1044017: 1044017
13 AGRN NM_198576.3(AGRN): c.2690C> T (p.Ala897Val) single nucleotide variant Conflicting interpretations of pathogenicity rs116836855 GRCh37 Chromosome 1, 981353: 981353
14 AGRN NM_198576.3(AGRN): c.2690C> T (p.Ala897Val) single nucleotide variant Conflicting interpretations of pathogenicity rs116836855 GRCh38 Chromosome 1, 1045973: 1045973
15 AGRN NM_198576.3(AGRN): c.4639G> A (p.Glu1547Lys) single nucleotide variant Conflicting interpretations of pathogenicity rs2799068 GRCh38 Chromosome 1, 1049690: 1049690
16 AGRN NM_198576.3(AGRN): c.4639G> A (p.Glu1547Lys) single nucleotide variant Conflicting interpretations of pathogenicity rs2799068 GRCh37 Chromosome 1, 985070: 985070
17 AGRN NM_198576.3(AGRN): c.729C> G (p.Gly243=) single nucleotide variant Benign rs191270495 GRCh38 Chromosome 1, 1041174: 1041174
18 AGRN NM_198576.3(AGRN): c.729C> G (p.Gly243=) single nucleotide variant Benign rs191270495 GRCh37 Chromosome 1, 976554: 976554
19 AGRN NM_198576.3(AGRN): c.738C> T (p.Asp246=) single nucleotide variant Likely benign rs536085218 GRCh38 Chromosome 1, 1041183: 1041183
20 AGRN NM_198576.3(AGRN): c.738C> T (p.Asp246=) single nucleotide variant Likely benign rs536085218 GRCh37 Chromosome 1, 976563: 976563
21 AGRN NM_198576.3(AGRN): c.773C> T (p.Thr258Ile) single nucleotide variant Benign/Likely benign rs200607541 GRCh38 Chromosome 1, 1041218: 1041218
22 AGRN NM_198576.3(AGRN): c.773C> T (p.Thr258Ile) single nucleotide variant Benign/Likely benign rs200607541 GRCh37 Chromosome 1, 976598: 976598
23 AGRN NM_198576.3(AGRN): c.1123G> T (p.Ala375Ser) single nucleotide variant Benign/Likely benign rs138031468 GRCh38 Chromosome 1, 1041648: 1041648
24 AGRN NM_198576.3(AGRN): c.1123G> T (p.Ala375Ser) single nucleotide variant Benign/Likely benign rs138031468 GRCh37 Chromosome 1, 977028: 977028
25 AGRN NM_198576.3(AGRN): c.1434G> A (p.Thr478=) single nucleotide variant Benign rs147346337 GRCh38 Chromosome 1, 1043288: 1043288
26 AGRN NM_198576.3(AGRN): c.1434G> A (p.Thr478=) single nucleotide variant Benign rs147346337 GRCh37 Chromosome 1, 978668: 978668
27 AGRN NM_198576.3(AGRN): c.1528G> A (p.Gly510Ser) single nucleotide variant Benign/Likely benign rs138288952 GRCh38 Chromosome 1, 1043382: 1043382
28 AGRN NM_198576.3(AGRN): c.1528G> A (p.Gly510Ser) single nucleotide variant Benign/Likely benign rs138288952 GRCh37 Chromosome 1, 978762: 978762
29 AGRN NM_198576.3(AGRN): c.1660G> A (p.Val554Met) single nucleotide variant Benign/Likely benign rs79016973 GRCh38 Chromosome 1, 1043594: 1043594
30 AGRN NM_198576.3(AGRN): c.1660G> A (p.Val554Met) single nucleotide variant Benign/Likely benign rs79016973 GRCh37 Chromosome 1, 978974: 978974
31 AGRN NM_198576.3(AGRN): c.2067G> A (p.Gln689=) single nucleotide variant Benign rs139886237 GRCh38 Chromosome 1, 1044176: 1044176
32 AGRN NM_198576.3(AGRN): c.2067G> A (p.Gln689=) single nucleotide variant Benign rs139886237 GRCh37 Chromosome 1, 979556: 979556
33 AGRN NM_198576.3(AGRN): c.2266G> A (p.Ala756Thr) single nucleotide variant Likely benign rs140764403 GRCh38 Chromosome 1, 1045172: 1045172
34 AGRN NM_198576.3(AGRN): c.2266G> A (p.Ala756Thr) single nucleotide variant Likely benign rs140764403 GRCh37 Chromosome 1, 980552: 980552
35 AGRN NM_198576.3(AGRN): c.2271G> A (p.Pro757=) single nucleotide variant Likely benign rs150123719 GRCh38 Chromosome 1, 1045177: 1045177
36 AGRN NM_198576.3(AGRN): c.2271G> A (p.Pro757=) single nucleotide variant Likely benign rs150123719 GRCh37 Chromosome 1, 980557: 980557
37 AGRN NM_198576.3(AGRN): c.2555A> G (p.Gln852Arg) single nucleotide variant Benign rs9697293 GRCh38 Chromosome 1, 1045751: 1045751
38 AGRN NM_198576.3(AGRN): c.2555A> G (p.Gln852Arg) single nucleotide variant Benign rs9697293 GRCh37 Chromosome 1, 981131: 981131
39 AGRN NM_198576.3(AGRN): c.2682C> T (p.Asp894=) single nucleotide variant Benign rs118105080 GRCh38 Chromosome 1, 1045965: 1045965
40 AGRN NM_198576.3(AGRN): c.2682C> T (p.Asp894=) single nucleotide variant Benign rs118105080 GRCh37 Chromosome 1, 981345: 981345
41 AGRN NM_198576.3(AGRN): c.3003C> T (p.Pro1001=) single nucleotide variant Likely benign rs375208869 GRCh38 Chromosome 1, 1046488: 1046488
42 AGRN NM_198576.3(AGRN): c.3003C> T (p.Pro1001=) single nucleotide variant Likely benign rs375208869 GRCh37 Chromosome 1, 981868: 981868
43 AGRN NM_198576.3(AGRN): c.3077C> A (p.Thr1026Asn) single nucleotide variant Benign/Likely benign rs3813188 GRCh38 Chromosome 1, 1046562: 1046562
44 AGRN NM_198576.3(AGRN): c.3077C> A (p.Thr1026Asn) single nucleotide variant Benign/Likely benign rs3813188 GRCh37 Chromosome 1, 981942: 981942
45 AGRN NM_198576.3(AGRN): c.3719C> T (p.Pro1240Leu) single nucleotide variant Likely benign rs142620337 GRCh38 Chromosome 1, 1047863: 1047863
46 AGRN NM_198576.3(AGRN): c.3719C> T (p.Pro1240Leu) single nucleotide variant Likely benign rs142620337 GRCh37 Chromosome 1, 983243: 983243
47 AGRN NM_198576.3(AGRN): c.4285C> T (p.Arg1429Cys) single nucleotide variant Benign/Likely benign rs201346452 GRCh38 Chromosome 1, 1049046: 1049046
48 AGRN NM_198576.3(AGRN): c.4285C> T (p.Arg1429Cys) single nucleotide variant Benign/Likely benign rs201346452 GRCh37 Chromosome 1, 984426: 984426
49 AGRN NM_198576.3(AGRN): c.4352C> T (p.Pro1451Leu) single nucleotide variant Likely benign rs144620006 GRCh38 Chromosome 1, 1049289: 1049289
50 AGRN NM_198576.3(AGRN): c.4352C> T (p.Pro1451Leu) single nucleotide variant Likely benign rs144620006 GRCh37 Chromosome 1, 984669: 984669

Expression for Myasthenic Syndrome, Congenital, 8

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

Pathways for Myasthenic Syndrome, Congenital, 8

GO Terms for Myasthenic Syndrome, Congenital, 8

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

# Name GO ID Score Top Affiliating Genes
1 cellular response to DNA damage stimulus GO:0006974 8.62 DTL TP53

Sources for Myasthenic Syndrome, Congenital, 8

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