CMS8
MCID: MYS076
MIFTS: 25

Myasthenic Syndrome, Congenital, 8 (CMS8)

Categories: Eye diseases, Fetal diseases, Genetic diseases, Immune 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 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, also known as myasthenic syndrome, congenital, with pre- and postsynaptic defects, is related to muscular disease, and has symptoms including facial paresis An important gene associated with Myasthenic Syndrome, Congenital, 8 is AGRN (Agrin). Affiliated tissues include eye, and 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 respiratory insufficiency 32 occasional (7.5%) HP:0002093
4 facial palsy 32 HP:0010628
5 narrow chest 32 HP:0000774
6 easy fatigability 32 HP:0003388
7 proximal muscle weakness 32 HP:0003701

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

MalaCards organs/tissues related to Myasthenic Syndrome, Congenital, 8:

41
Eye

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 530)
# 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.1058A> G (p.Gln353Arg) single nucleotide variant Benign rs150359724 GRCh37 Chromosome 1, 976963: 976963
8 AGRN NM_198576.3(AGRN): c.1058A> G (p.Gln353Arg) single nucleotide variant Benign rs150359724 GRCh38 Chromosome 1, 1041583: 1041583
9 AGRN NM_198576.3(AGRN): c.2025C> G (p.Gly675=) single nucleotide variant Benign rs28484890 GRCh37 Chromosome 1, 979514: 979514
10 AGRN NM_198576.3(AGRN): c.2025C> G (p.Gly675=) single nucleotide variant Benign rs28484890 GRCh38 Chromosome 1, 1044134: 1044134
11 AGRN NM_198576.3(AGRN): c.2183A> T (p.Glu728Val) single nucleotide variant Benign rs113288277 GRCh37 Chromosome 1, 979748: 979748
12 AGRN NM_198576.3(AGRN): c.2183A> T (p.Glu728Val) single nucleotide variant Benign rs113288277 GRCh38 Chromosome 1, 1044368: 1044368
13 AGRN NM_198576.3(AGRN): c.2406C> T (p.Gly802=) single nucleotide variant Benign rs75774767 GRCh37 Chromosome 1, 980773: 980773
14 AGRN NM_198576.3(AGRN): c.2406C> T (p.Gly802=) single nucleotide variant Benign rs75774767 GRCh38 Chromosome 1, 1045393: 1045393
15 AGRN NM_198576.3(AGRN): c.261C> T (p.Asp87=) single nucleotide variant Benign rs6657048 GRCh37 Chromosome 1, 957640: 957640
16 AGRN NM_198576.3(AGRN): c.261C> T (p.Asp87=) single nucleotide variant Benign rs6657048 GRCh38 Chromosome 1, 1022260: 1022260
17 AGRN NM_198576.3(AGRN): c.3264G> C (p.Leu1088Phe) single nucleotide variant Benign/Likely benign rs150132566 GRCh37 Chromosome 1, 982213: 982213
18 AGRN NM_198576.3(AGRN): c.3264G> C (p.Leu1088Phe) single nucleotide variant Benign/Likely benign rs150132566 GRCh38 Chromosome 1, 1046833: 1046833
19 AGRN NM_198576.3(AGRN): c.3404A> G (p.Gln1135Arg) single nucleotide variant Benign rs142416636 GRCh37 Chromosome 1, 982722: 982722
20 AGRN NM_198576.3(AGRN): c.3404A> G (p.Gln1135Arg) single nucleotide variant Benign rs142416636 GRCh38 Chromosome 1, 1047342: 1047342
21 AGRN NM_198576.3(AGRN): c.3465T> C (p.Ala1155=) single nucleotide variant Benign/Likely benign rs146358566 GRCh37 Chromosome 1, 982783: 982783
22 AGRN NM_198576.3(AGRN): c.3465T> C (p.Ala1155=) single nucleotide variant Benign/Likely benign rs146358566 GRCh38 Chromosome 1, 1047403: 1047403
23 AGRN NM_198576.3(AGRN): c.3570C> T (p.Arg1190=) single nucleotide variant Benign rs75361935 GRCh37 Chromosome 1, 983006: 983006
24 AGRN NM_198576.3(AGRN): c.3570C> T (p.Arg1190=) single nucleotide variant Benign rs75361935 GRCh38 Chromosome 1, 1047626: 1047626
25 AGRN NM_198576.3(AGRN): c.3866C> T (p.Pro1289Leu) single nucleotide variant Benign/Likely benign rs139294803 GRCh37 Chromosome 1, 983506: 983506
26 AGRN NM_198576.3(AGRN): c.3866C> T (p.Pro1289Leu) single nucleotide variant Benign/Likely benign rs139294803 GRCh38 Chromosome 1, 1048126: 1048126
27 AGRN NM_198576.3(AGRN): c.3964C> T (p.Arg1322Trp) single nucleotide variant Benign/Likely benign rs184970403 GRCh37 Chromosome 1, 983604: 983604
28 AGRN NM_198576.3(AGRN): c.3964C> T (p.Arg1322Trp) single nucleotide variant Benign/Likely benign rs184970403 GRCh38 Chromosome 1, 1048224: 1048224
29 AGRN NM_198576.3(AGRN): c.3972G> A (p.Pro1324=) single nucleotide variant Benign rs201483077 GRCh37 Chromosome 1, 983612: 983612
30 AGRN NM_198576.3(AGRN): c.3972G> A (p.Pro1324=) single nucleotide variant Benign rs201483077 GRCh38 Chromosome 1, 1048232: 1048232
31 AGRN NM_198576.3(AGRN): c.4452C> T (p.Thr1484=) single nucleotide variant Benign rs75767981 GRCh37 Chromosome 1, 984769: 984769
32 AGRN NM_198576.3(AGRN): c.4452C> T (p.Thr1484=) single nucleotide variant Benign rs75767981 GRCh38 Chromosome 1, 1049389: 1049389
33 AGRN NM_198576.3(AGRN): c.4540G> A (p.Ala1514Thr) single nucleotide variant Benign/Likely benign rs111818381 GRCh37 Chromosome 1, 984971: 984971
34 AGRN NM_198576.3(AGRN): c.4540G> A (p.Ala1514Thr) single nucleotide variant Benign/Likely benign rs111818381 GRCh38 Chromosome 1, 1049591: 1049591
35 AGRN NM_198576.3(AGRN): c.4740C> T (p.Arg1580=) single nucleotide variant Benign rs115019873 GRCh37 Chromosome 1, 985171: 985171
36 AGRN NM_198576.3(AGRN): c.4740C> T (p.Arg1580=) single nucleotide variant Benign rs115019873 GRCh38 Chromosome 1, 1049791: 1049791
37 AGRN NM_198576.3(AGRN): c.4996G> A (p.Val1666Ile) single nucleotide variant Benign rs17160775 GRCh37 Chromosome 1, 985826: 985826
38 AGRN NM_198576.3(AGRN): c.4996G> A (p.Val1666Ile) single nucleotide variant Benign rs17160775 GRCh38 Chromosome 1, 1050446: 1050446
39 AGRN NM_198576.3(AGRN): c.5070C> T (p.Phe1690=) single nucleotide variant Benign rs17160776 GRCh37 Chromosome 1, 985900: 985900
40 AGRN NM_198576.3(AGRN): c.5070C> T (p.Phe1690=) single nucleotide variant Benign rs17160776 GRCh38 Chromosome 1, 1050520: 1050520
41 AGRN NM_198576.3(AGRN): c.5353G> A (p.Asp1785Asn) single nucleotide variant Conflicting interpretations of pathogenicity rs144245019 GRCh37 Chromosome 1, 986732: 986732
42 AGRN NM_198576.3(AGRN): c.5353G> A (p.Asp1785Asn) single nucleotide variant Conflicting interpretations of pathogenicity rs144245019 GRCh38 Chromosome 1, 1051352: 1051352
43 AGRN NM_198576.3(AGRN): c.5598C> T (p.Thr1866=) single nucleotide variant Benign rs17778478 GRCh37 Chromosome 1, 987142: 987142
44 AGRN NM_198576.3(AGRN): c.5598C> T (p.Thr1866=) single nucleotide variant Benign rs17778478 GRCh38 Chromosome 1, 1051762: 1051762
45 AGRN NM_198576.3(AGRN): c.5726G> C (p.Ser1909Thr) single nucleotide variant Benign/Likely benign rs74685771 GRCh37 Chromosome 1, 989207: 989207
46 AGRN NM_198576.3(AGRN): c.5726G> C (p.Ser1909Thr) single nucleotide variant Benign/Likely benign rs74685771 GRCh38 Chromosome 1, 1053827: 1053827
47 AGRN NM_198576.3(AGRN): c.804C> T (p.Ala268=) single nucleotide variant Benign rs113789806 GRCh37 Chromosome 1, 976629: 976629
48 AGRN NM_198576.3(AGRN): c.804C> T (p.Ala268=) single nucleotide variant Benign rs113789806 GRCh38 Chromosome 1, 1041249: 1041249
49 AGRN NM_198576.3(AGRN): c.2457G> C (p.Gly819=) single nucleotide variant Benign/Likely benign rs112039851 GRCh38 Chromosome 1, 1045444: 1045444
50 AGRN NM_198576.3(AGRN): c.2457G> C (p.Gly819=) single nucleotide variant Benign/Likely benign rs112039851 GRCh37 Chromosome 1, 980824: 980824

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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