MCID: MYS078
MIFTS: 40

Myasthenic Syndrome, Congenital, 14

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

Aliases & Classifications for Myasthenic Syndrome, Congenital, 14

MalaCards integrated aliases for Myasthenic Syndrome, Congenital, 14:

Name: Myasthenic Syndrome, Congenital, 14 57 75 29 6
Cmsta3 57 12 75
Cms14 57 12 75
Myasthenic Syndrome, Congenital, 14, with Tubular Aggregates 57 75
Myasthenic Syndrome, Congenital, with Tubular Aggregates 3 57 73
Congenital Myasthenic Syndrome 14 12 15
Myasthenic Syndrome, Congenital, with Tubular Aggregates 3; Cmsta3 57
Myasthenic Syndrome, Congenital, Type 14, with Tubular Aggregates 40
Myasthenic Syndrome, Congenital, with Tubular Aggregates, 3 75
Congenital Myasthenic Syndrome 14, with Tubular Aggregates 12
Congenital Myasthenic Syndrome with Tubular Aggregates 3 12

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
slowly progressive
onset in first decade
some patients may become wheelchair-bound
favorable response to anticholinesterase medication
three unrelated families have been reported (last curated february 2015)


HPO:

32
myasthenic syndrome, congenital, 14:
Onset and clinical course slow progression
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Myasthenic Syndrome, Congenital, 14

UniProtKB/Swiss-Prot : 75 Myasthenic syndrome, congenital, 14: 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. CMS14 is an autosomal recessive form characterized by onset of limb-girdle muscle weakness in early childhood. The disorder is slowly progressive, and some patients may become wheelchair-bound.

MalaCards based summary : Myasthenic Syndrome, Congenital, 14, also known as cmsta3, is related to primary mediastinal large b-cell lymphoma and spinal chordoma, and has symptoms including waddling gait An important gene associated with Myasthenic Syndrome, Congenital, 14 is ALG2 (ALG2, Alpha-1,3/1,6-Mannosyltransferase), and among its related pathways/superpathways are Innate Immune System and Regulation of IFNA signaling. Related phenotypes are high palate and scoliosis

Disease Ontology : 12 A congenital myasthenic syndrome characterized by autosomal recessive inheritance of slowly progressive development of limb-girdle muscle weakness with onset in early childhood that has material basis in homozygous mutation in the ALG2 gene on chromosome 9q22.

OMIM : 57 Congenital myasthenic syndrome-14 is an autosomal recessive neuromuscular disorder characterized by onset of limb-girdle muscle weakness in early childhood. The disorder is slowly progressive, and some patients may become wheelchair-bound. There is no respiratory or cardiac involvement. Treatment with anticholinesterase medication may be beneficial (summary by Cossins et al., 2013). For a discussion of genetic heterogeneity of CMS, see CMS1A (601462). (616228)

Related Diseases for Myasthenic Syndrome, Congenital, 14

Graphical network of the top 20 diseases related to Myasthenic Syndrome, Congenital, 14:



Diseases related to Myasthenic Syndrome, Congenital, 14

Symptoms & Phenotypes for Myasthenic Syndrome, Congenital, 14

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
waddling gait
delayed motor development (in some patients)
learning difficulties, mild (1 family)

Skeletal:
joint contractures (in some patients)
distal joint laxity (in some patients)

Muscle Soft Tissue:
gower sign
muscle weakness, proximal greater than distal
muscle biopsy shows type 1 fiber predominance
hypotonia (in some patients)
limb-girdle muscle weakness
more
Skeletal Feet:
pes planus (in some patients)

Skeletal Spine:
scoliosis (in some patients)
lordosis (in some patients)

Head And Neck Mouth:
high-arched palate (in some patients)

Chest Ribs Sternum Clavicles And Scapulae:
scapular winging (in some patients)

Laboratory Abnormalities:
mildly increased serum creatine kinase (in some patients)
serum transferrin shows normal or mild hypo-glycosylation


Clinical features from OMIM:

616228

Human phenotypes related to Myasthenic Syndrome, Congenital, 14:

32 (show all 14)
# Description HPO Frequency HPO Source Accession
1 high palate 32 occasional (7.5%) HP:0000218
2 scoliosis 32 occasional (7.5%) HP:0002650
3 hyperlordosis 32 occasional (7.5%) HP:0003307
4 pes planus 32 occasional (7.5%) HP:0001763
5 flexion contracture 32 occasional (7.5%) HP:0001371
6 scapular winging 32 occasional (7.5%) HP:0003691
7 ragged-red muscle fibers 32 occasional (7.5%) HP:0003200
8 mildly elevated creatine phosphokinase 32 occasional (7.5%) HP:0008180
9 motor delay 32 occasional (7.5%) HP:0001270
10 fatigable weakness 32 HP:0003473
11 generalized hypotonia 32 occasional (7.5%) HP:0001290
12 waddling gait 32 HP:0002515
13 gowers sign 32 HP:0003391
14 limb-girdle muscle weakness 32 HP:0003325

UMLS symptoms related to Myasthenic Syndrome, Congenital, 14:


waddling gait

MGI Mouse Phenotypes related to Myasthenic Syndrome, Congenital, 14:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 9.8 ALG2 CD274 JAK2 MYC PDCD1LG2 PIK3CA
2 immune system MP:0005387 9.63 CD274 JAK2 MYC PDCD1LG2 PIK3CA PPP3CA
3 mortality/aging MP:0010768 9.5 ALG2 CD274 JAK2 MYC PDCD1LG2 PIK3CA
4 neoplasm MP:0002006 8.92 PIK3CA JAK2 MYC PDCD1LG2

Drugs & Therapeutics for Myasthenic Syndrome, Congenital, 14

Search Clinical Trials , NIH Clinical Center for Myasthenic Syndrome, Congenital, 14

Genetic Tests for Myasthenic Syndrome, Congenital, 14

Genetic tests related to Myasthenic Syndrome, Congenital, 14:

# Genetic test Affiliating Genes
1 Myasthenic Syndrome, Congenital, 14 29 ALG2

Anatomical Context for Myasthenic Syndrome, Congenital, 14

Publications for Myasthenic Syndrome, Congenital, 14

Variations for Myasthenic Syndrome, Congenital, 14

UniProtKB/Swiss-Prot genetic disease variations for Myasthenic Syndrome, Congenital, 14:

75
# Symbol AA change Variation ID SNP ID
1 ALG2 p.Val68Gly VAR_073332 rs730882051

ClinVar genetic disease variations for Myasthenic Syndrome, Congenital, 14:

6
(show all 46)
# Gene Variation Type Significance SNP ID Assembly Location
1 ALG2 NM_033087.3(ALG2): c.17G> C (p.Gly6Ala) single nucleotide variant Conflicting interpretations of pathogenicity rs180849348 GRCh37 Chromosome 9, 101984160: 101984160
2 ALG2 NM_033087.3(ALG2): c.17G> C (p.Gly6Ala) single nucleotide variant Conflicting interpretations of pathogenicity rs180849348 GRCh38 Chromosome 9, 99221878: 99221878
3 ALG2 NM_033087.3(ALG2): c.214_224delGGGGACTGGCTinsAGTCCCCG (p.Gly72_Leu75delinsSerProArg) indel Pathogenic rs730882123 GRCh37 Chromosome 9, 101983953: 101983963
4 ALG2 NM_033087.3(ALG2): c.214_224delGGGGACTGGCTinsAGTCCCCG (p.Gly72_Leu75delinsSerProArg) indel Pathogenic rs730882123 GRCh38 Chromosome 9, 99221671: 99221681
5 ALG2 NM_033087.3(ALG2): c.203T> G (p.Val68Gly) single nucleotide variant Pathogenic rs730882051 GRCh37 Chromosome 9, 101983974: 101983974
6 ALG2 NM_033087.3(ALG2): c.203T> G (p.Val68Gly) single nucleotide variant Pathogenic rs730882051 GRCh38 Chromosome 9, 99221692: 99221692
7 ALG2 NM_033087.3(ALG2): c.84C> G (p.Gly28=) single nucleotide variant Benign/Likely benign rs61744789 GRCh37 Chromosome 9, 101984093: 101984093
8 ALG2 NM_033087.3(ALG2): c.84C> G (p.Gly28=) single nucleotide variant Benign/Likely benign rs61744789 GRCh38 Chromosome 9, 99221811: 99221811
9 ALG2 NM_033087.3(ALG2): c.30C> G (p.Asp10Glu) single nucleotide variant Benign/Likely benign rs7023652 GRCh37 Chromosome 9, 101984147: 101984147
10 ALG2 NM_033087.3(ALG2): c.30C> G (p.Asp10Glu) single nucleotide variant Benign/Likely benign rs7023652 GRCh38 Chromosome 9, 99221865: 99221865
11 ALG2 NM_033087.3(ALG2): c.129C> G (p.Arg43=) single nucleotide variant Benign/Likely benign rs35055733 GRCh37 Chromosome 9, 101984048: 101984048
12 ALG2 NM_033087.3(ALG2): c.129C> G (p.Arg43=) single nucleotide variant Benign/Likely benign rs35055733 GRCh38 Chromosome 9, 99221766: 99221766
13 ALG2 NM_033087.3(ALG2): c.1132C> T (p.Arg378Cys) single nucleotide variant Uncertain significance rs56393253 GRCh37 Chromosome 9, 101980335: 101980335
14 ALG2 NM_033087.3(ALG2): c.1132C> T (p.Arg378Cys) single nucleotide variant Uncertain significance rs56393253 GRCh38 Chromosome 9, 99218053: 99218053
15 ALG2 NM_033087.3(ALG2): c.1174G> A (p.Ala392Thr) single nucleotide variant Uncertain significance rs138258236 GRCh38 Chromosome 9, 99218011: 99218011
16 ALG2 NM_033087.3(ALG2): c.1174G> A (p.Ala392Thr) single nucleotide variant Uncertain significance rs138258236 GRCh37 Chromosome 9, 101980293: 101980293
17 ALG2 NM_033087.3(ALG2): c.159C> T (p.His53=) single nucleotide variant Conflicting interpretations of pathogenicity rs527683080 GRCh37 Chromosome 9, 101984018: 101984018
18 ALG2 NM_033087.3(ALG2): c.159C> T (p.His53=) single nucleotide variant Conflicting interpretations of pathogenicity rs527683080 GRCh38 Chromosome 9, 99221736: 99221736
19 ALG2 NM_033087.3(ALG2): c.304C> T (p.Leu102=) single nucleotide variant Conflicting interpretations of pathogenicity rs749236548 GRCh37 Chromosome 9, 101983873: 101983873
20 ALG2 NM_033087.3(ALG2): c.304C> T (p.Leu102=) single nucleotide variant Conflicting interpretations of pathogenicity rs749236548 GRCh38 Chromosome 9, 99221591: 99221591
21 ALG2 NM_033087.3(ALG2): c.288C> T (p.Phe96=) single nucleotide variant Benign/Likely benign rs542863968 GRCh38 Chromosome 9, 99221607: 99221607
22 ALG2 NM_033087.3(ALG2): c.288C> T (p.Phe96=) single nucleotide variant Benign/Likely benign rs542863968 GRCh37 Chromosome 9, 101983889: 101983889
23 ALG2 NM_033087.3(ALG2): c.167C> T (p.Pro56Leu) single nucleotide variant Benign rs201959100 GRCh37 Chromosome 9, 101984010: 101984010
24 ALG2 NM_033087.3(ALG2): c.167C> T (p.Pro56Leu) single nucleotide variant Benign rs201959100 GRCh38 Chromosome 9, 99221728: 99221728
25 ALG2 NM_033087.3(ALG2): c.1055_1056delCCinsTGA (p.Ser352Leufs) indel Uncertain significance GRCh37 Chromosome 9, 101980411: 101980412
26 ALG2 NM_033087.3(ALG2): c.1055_1056delCCinsTGA (p.Ser352Leufs) indel Uncertain significance GRCh38 Chromosome 9, 99218129: 99218130
27 ALG2 NM_033087.3(ALG2): c.443A> G (p.Asp148Gly) single nucleotide variant Uncertain significance rs369670496 GRCh37 Chromosome 9, 101981024: 101981024
28 ALG2 NM_033087.3(ALG2): c.443A> G (p.Asp148Gly) single nucleotide variant Uncertain significance rs369670496 GRCh38 Chromosome 9, 99218742: 99218742
29 ALG2 NM_033087.3(ALG2): c.729A> T (p.Ala243=) single nucleotide variant Likely benign rs748947069 GRCh37 Chromosome 9, 101980738: 101980738
30 ALG2 NM_033087.3(ALG2): c.729A> T (p.Ala243=) single nucleotide variant Likely benign rs748947069 GRCh38 Chromosome 9, 99218456: 99218456
31 ALG2 NM_033087.3(ALG2): c.348+6G> A single nucleotide variant Uncertain significance rs368075764 GRCh37 Chromosome 9, 101983823: 101983823
32 ALG2 NM_033087.3(ALG2): c.348+6G> A single nucleotide variant Uncertain significance rs368075764 GRCh38 Chromosome 9, 99221541: 99221541
33 ALG2 NM_033087.3(ALG2): c.44C> A (p.Pro15Gln) single nucleotide variant Uncertain significance rs757920586 GRCh38 Chromosome 9, 99221851: 99221851
34 ALG2 NM_033087.3(ALG2): c.44C> A (p.Pro15Gln) single nucleotide variant Uncertain significance rs757920586 GRCh37 Chromosome 9, 101984133: 101984133
35 ALG2 NM_033087.3(ALG2): c.219C> G (p.Asp73Glu) single nucleotide variant Uncertain significance rs755705607 GRCh37 Chromosome 9, 101983958: 101983958
36 ALG2 NM_033087.3(ALG2): c.219C> G (p.Asp73Glu) single nucleotide variant Uncertain significance rs755705607 GRCh38 Chromosome 9, 99221676: 99221676
37 ALG2 NM_033087.3(ALG2): c.10G> A (p.Glu4Lys) single nucleotide variant Uncertain significance GRCh38 Chromosome 9, 99221885: 99221885
38 ALG2 NM_033087.3(ALG2): c.10G> A (p.Glu4Lys) single nucleotide variant Uncertain significance GRCh37 Chromosome 9, 101984167: 101984167
39 ALG2 NM_033087.3(ALG2): c.399C> G (p.Ile133Met) single nucleotide variant Uncertain significance rs371772900 GRCh37 Chromosome 9, 101981068: 101981068
40 ALG2 NM_033087.3(ALG2): c.399C> G (p.Ile133Met) single nucleotide variant Uncertain significance rs371772900 GRCh38 Chromosome 9, 99218786: 99218786
41 ALG2 NM_033087.3(ALG2): c.339G> A (p.Val113=) single nucleotide variant Likely benign GRCh38 Chromosome 9, 99221556: 99221556
42 ALG2 NM_033087.3(ALG2): c.339G> A (p.Val113=) single nucleotide variant Likely benign GRCh37 Chromosome 9, 101983838: 101983838
43 ALG2 NM_033087.3(ALG2): c.1200T> C (p.Pro400=) single nucleotide variant Likely benign rs764916897 GRCh37 Chromosome 9, 101980267: 101980267
44 ALG2 NM_033087.3(ALG2): c.1200T> C (p.Pro400=) single nucleotide variant Likely benign rs764916897 GRCh38 Chromosome 9, 99217985: 99217985
45 ALG2 NM_033087.3(ALG2): c.92G> C (p.Arg31Pro) single nucleotide variant Uncertain significance GRCh37 Chromosome 9, 101984085: 101984085
46 ALG2 NM_033087.3(ALG2): c.92G> C (p.Arg31Pro) single nucleotide variant Uncertain significance GRCh38 Chromosome 9, 99221803: 99221803

Expression for Myasthenic Syndrome, Congenital, 14

Search GEO for disease gene expression data for Myasthenic Syndrome, Congenital, 14.

Pathways for Myasthenic Syndrome, Congenital, 14

Pathways related to Myasthenic Syndrome, Congenital, 14 according to GeneCards Suite gene sharing:

(show all 29)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.62 CD274 JAK2 MYC PDCD1LG2 PIK3CA PPP3CA
2
Show member pathways
12.34 JAK2 MYC PIK3CA
3
Show member pathways
12.32 JAK2 MYC PIK3CA
4
Show member pathways
12.29 JAK2 PIK3CA PPP3CA
5
Show member pathways
12.25 JAK2 MYC PIK3CA
6
Show member pathways
12.18 JAK2 MYC PIK3CA
7
Show member pathways
12.14 JAK2 MYC PIK3CA PPP3CA
8 12.12 MYC PIK3CA PPP3CA
9
Show member pathways
12.09 JAK2 PIK3CA PPP3CA
10 12.07 CD274 JAK2 PDCD1LG2 PPP3CA
11
Show member pathways
12.06 MYC PIK3CA PPP3CA
12
Show member pathways
11.91 CD274 PDCD1LG2 PIK3CA
13 11.84 MYC PIK3CA PPP3CA
14
Show member pathways
11.82 JAK2 MYC PIK3CA
15 11.75 JAK2 MYC PIK3CA
16
Show member pathways
11.71 JAK2 MYC PIK3CA
17
Show member pathways
11.48 JAK2 MYC PIK3CA
18
Show member pathways
11.47 MYC PIK3CA
19 11.46 MYC PIK3CA
20 11.44 MYC PIK3CA
21 11.42 JAK2 PIK3CA
22 11.38 CD274 PDCD1LG2
23 11.34 MYC PIK3CA
24 11.3 JAK2 PIK3CA
25 11.27 JAK2 PIK3CA
26
Show member pathways
11.2 JAK2 PIK3CA
27 11.16 JAK2 MYC PIK3CA
28
Show member pathways
10.95 JAK2 MYC PIK3CA PPP3CA
29 10.8 JAK2 MYC PIK3CA

GO Terms for Myasthenic Syndrome, Congenital, 14

Cellular components related to Myasthenic Syndrome, Congenital, 14 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 membrane GO:0016020 9.56 ALG2 CD274 JAK2 MYC PDCD1LG2 PIK3CA
2 endomembrane system GO:0012505 8.8 CD274 JAK2 PDCD1LG2

Biological processes related to Myasthenic Syndrome, Congenital, 14 according to GeneCards Suite gene sharing:

(show all 12)
# Name GO ID Score Top Affiliating Genes
1 cytokine-mediated signaling pathway GO:0019221 9.58 JAK2 MYC PIK3CA
2 cellular response to drug GO:0035690 9.51 MYC PPP3CA
3 glucose metabolic process GO:0006006 9.49 MYC PIK3CA
4 positive regulation of T cell proliferation GO:0042102 9.48 CD274 PDCD1LG2
5 cellular response to glucose stimulus GO:0071333 9.46 PIK3CA PPP3CA
6 response to calcium ion GO:0051592 9.43 ALG2 PPP3CA
7 negative regulation of T cell proliferation GO:0042130 9.37 CD274 PDCD1LG2
8 positive regulation of DNA binding GO:0043388 9.32 JAK2 MYC
9 negative regulation of interferon-gamma production GO:0032689 9.26 CD274 PDCD1LG2
10 negative regulation of interleukin-10 production GO:0032693 9.16 CD274 PDCD1LG2
11 negative regulation of activated T cell proliferation GO:0046007 8.96 CD274 PDCD1LG2
12 T cell costimulation GO:0031295 8.8 CD274 PDCD1LG2 PIK3CA

Molecular functions related to Myasthenic Syndrome, Congenital, 14 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 insulin receptor substrate binding GO:0043560 8.62 JAK2 PIK3CA

Sources for Myasthenic Syndrome, Congenital, 14

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
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30 HGMD
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32 HPO
33 ICD10
34 ICD10 via Orphanet
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44 MeSH
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58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
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74 UMLS via Orphanet
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