CMS14
MCID: MYS078
MIFTS: 39

Myasthenic Syndrome, Congenital, 14 (CMS14)

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

Aliases & Classifications for Myasthenic Syndrome, Congenital, 14

MalaCards integrated aliases for Myasthenic Syndrome, Congenital, 14:

Name: Myasthenic Syndrome, Congenital, 14 56 73 29 6
Myasthenic Syndrome, Congenital, 14, with Tubular Aggregates 56 73 29
Cmsta3 56 12 73
Cms14 56 12 73
Myasthenic Syndrome, Congenital, with Tubular Aggregates 3 56 71
Congenital Myasthenic Syndrome 14 12 15
Myasthenic Syndrome, Congenital, with Tubular Aggregates 3; Cmsta3 56
Myasthenic Syndrome, Congenital, Type 14, with Tubular Aggregates 39
Myasthenic Syndrome, Congenital, with Tubular Aggregates, 3 73
Congenital Myasthenic Syndrome 14, with Tubular Aggregates 12
Congenital Myasthenic Syndrome with Tubular Aggregates 3 12

Characteristics:

OMIM:

56
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:

31
myasthenic syndrome, congenital, 14:
Inheritance autosomal recessive inheritance
Onset and clinical course slow progression


Classifications:



Summaries for Myasthenic Syndrome, Congenital, 14

UniProtKB/Swiss-Prot : 73 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 myasthenic syndrome, congenital, 14, with tubular aggregates, is related to congenital myasthenic syndromes with glycosylation defect and congenital muscular dystrophy-dystroglycanopathy a14, 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 EGFR Transactivation by Gastrin and MNAR-PELP1 and Estrogen Receptor Interaction. Related phenotypes are scoliosis and pes planus

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 : 56 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

Diseases in the Congenital Myasthenic Syndrome family:

Myasthenic Syndrome, Congenital, 10 Myasthenic Syndrome, Congenital, 5
Myasthenic Syndrome, Congenital, 12 Myasthenic Syndrome, Congenital, 16
Myasthenic Syndrome, Congenital, 13 Myasthenic Syndrome, Congenital, 8
Myasthenic Syndrome, Congenital, 22 Myasthenic Syndrome, Congenital, 15
Myasthenic Syndrome, Congenital, 14 Myasthenic Syndrome, Congenital, 17
Myasthenic Syndrome, Congenital, 18 Myasthenic Syndrome, Congenital, 19

Diseases related to Myasthenic Syndrome, Congenital, 14 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 57)
# Related Disease Score Top Affiliating Genes
1 congenital myasthenic syndromes with glycosylation defect 10.4 ALG2 ALG14
2 congenital muscular dystrophy-dystroglycanopathy a14 10.3 CCDC78 ALG14
3 signet ring basal cell carcinoma 10.3 KRAS HRAS
4 trachea carcinoma in situ 10.3 KRAS HRAS
5 cobblestone retinal degeneration 10.3 KRAS HRAS
6 nasal cavity adenocarcinoma 10.3 KRAS HRAS
7 ampulla of vater neoplasm 10.3 KRAS HRAS
8 descending colon cancer 10.3 KRAS HRAS
9 periampullary adenoma 10.3 KRAS HRAS
10 adenosquamous lung carcinoma 10.3 KRAS HRAS
11 acneiform dermatitis 10.3 KRAS HRAS
12 appendiceal neoplasm 10.3 KRAS HRAS
13 gallbladder benign neoplasm 10.3 KRAS HRAS
14 myh-associated polyposis 10.3 KRAS HRAS
15 appendix adenocarcinoma 10.3 KRAS HRAS
16 mucinous lung adenocarcinoma 10.3 KRAS HRAS
17 wolffian duct adenocarcinoma 10.3 KRAS HRAS
18 ascending colon cancer 10.2 KRAS HRAS
19 biliary tract benign neoplasm 10.2 KRAS HRAS
20 tumor of exocrine pancreas 10.2 KRAS HRAS
21 pancreatic acinar cell adenocarcinoma 10.2 KRAS HRAS
22 endosalpingiosis 10.2 KRAS HRAS
23 core binding factor acute myeloid leukemia 10.2 KRAS HRAS
24 lung carcinoma in situ 10.2 KRAS HRAS
25 appendix disease 10.2 KRAS HRAS
26 fructose intolerance, hereditary 10.2 ALG2 ALG14
27 paronychia 10.2 KRAS HRAS
28 duodenum adenocarcinoma 10.2 KRAS HRAS
29 pulmonary adenocarcinoma in situ 10.2 KRAS HRAS
30 bile duct cysts 10.2 KRAS HRAS
31 papillary adenoma 10.2 KRAS HRAS
32 appendix cancer 10.2 KRAS HRAS
33 large intestine adenocarcinoma 10.2 KRAS HRAS
34 oculoectodermal syndrome 10.2 KRAS HRAS
35 lung non-squamous non-small cell carcinoma 10.1 KRAS HRAS
36 rectosigmoid cancer 10.1 KRAS HRAS
37 transverse colon cancer 10.1 SIL1 KRAS HRAS
38 spinocerebellar ataxia, autosomal recessive 10 10.1 MYO9A ALG14
39 signet ring cell adenocarcinoma 10.1 SIL1 KRAS HRAS
40 rectum adenocarcinoma 10.1 SIL1 KRAS HRAS
41 colonic benign neoplasm 10.1 SIL1 KRAS HRAS
42 nasal cavity cancer 10.1 KRAS HRAS
43 small intestine cancer 10.1 SIL1 KRAS HRAS
44 intestinal benign neoplasm 10.1 SIL1 KRAS HRAS
45 female reproductive endometrioid cancer 10.1 KRAS HRAS
46 skin papilloma 10.0 KRAS HRAS
47 walker-warburg syndrome 10.0 APOL4 ALG2 ALG14
48 anus cancer 10.0 KRAS HRAS
49 phencyclidine abuse 10.0 APOL4 APOL2
50 duodenum cancer 10.0 KRAS HRAS

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

Human phenotypes related to Myasthenic Syndrome, Congenital, 14:

31 (show all 15)
# Description HPO Frequency HPO Source Accession
1 scoliosis 31 occasional (7.5%) HP:0002650
2 pes planus 31 occasional (7.5%) HP:0001763
3 flexion contracture 31 occasional (7.5%) HP:0001371
4 hyperlordosis 31 occasional (7.5%) HP:0003307
5 high palate 31 occasional (7.5%) HP:0000218
6 scapular winging 31 occasional (7.5%) HP:0003691
7 ragged-red muscle fibers 31 occasional (7.5%) HP:0003200
8 motor delay 31 occasional (7.5%) HP:0001270
9 generalized hypotonia 31 occasional (7.5%) HP:0001290
10 distal joint laxity 31 occasional (7.5%) HP:0020152
11 mildly elevated creatine kinase 31 occasional (7.5%) HP:0008180
12 waddling gait 31 HP:0002515
13 fatigable weakness 31 HP:0003473
14 gowers sign 31 HP:0003391
15 limb-girdle muscle weakness 31 HP:0003325

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
waddling gait
delayed motor development (in some patients)
learning difficulties, mild (1 family)

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)

Muscle Soft Tissue:
gowers sign
limb-girdle muscle weakness
muscle weakness, proximal greater than distal
muscle biopsy shows type 1 fiber predominance
hypotonia (in some patients)
more
Skeletal:
joint contractures (in some patients)
distal joint laxity (in some patients)

Skeletal Feet:
pes planus (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

UMLS symptoms related to Myasthenic Syndrome, Congenital, 14:


waddling gait

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
2 Myasthenic Syndrome, Congenital, 14, with Tubular Aggregates 29

Anatomical Context for Myasthenic Syndrome, Congenital, 14

Publications for Myasthenic Syndrome, Congenital, 14

Articles related to Myasthenic Syndrome, Congenital, 14:

# Title Authors PMID Year
1
Clinical and pathological heterogeneity of a congenital disorder of glycosylation manifesting as a myasthenic/myopathic syndrome. 6 56
24461433 2014
2
Congenital myasthenic syndromes due to mutations in ALG2 and ALG14. 56 6
23404334 2013
3
Congenital Myasthenic Syndromes 6
20301347 2003

Variations for Myasthenic Syndrome, Congenital, 14

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

6 (show top 50) (show all 63) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 ALG2 NM_033087.4(ALG2):c.214_224delinsAGTCCCCG (p.Gly72_Leu75delinsSerProArg)indel Pathogenic 183018 rs730882123 9:101983953-101983963 9:99221671-99221681
2 ALG2 NM_033087.4(ALG2):c.203T>G (p.Val68Gly)SNV Pathogenic 183019 rs730882051 9:101983974-101983974 9:99221692-99221692
3 ALG2 NM_033087.4(ALG2):c.1040del (p.Gly347fs)deletion Likely pathogenic 2699 rs387906281 9:101980427-101980427 9:99218145-99218145
4 ALG2 NM_033087.4(ALG2):c.760T>C (p.Leu254=)SNV Conflicting interpretations of pathogenicity 96238 rs62562374 9:101980707-101980707 9:99218425-99218425
5 ALG2 NM_033087.4(ALG2):c.17G>C (p.Gly6Ala)SNV Conflicting interpretations of pathogenicity 166675 rs180849348 9:101984160-101984160 9:99221878-99221878
6 ALG2 NM_033087.4(ALG2):c.484A>G (p.Ile162Val)SNV Conflicting interpretations of pathogenicity 364208 rs529195050 9:101980983-101980983 9:99218701-99218701
7 ALG2 NM_033087.4(ALG2):c.304C>T (p.Leu102=)SNV Conflicting interpretations of pathogenicity 364211 rs749236548 9:101983873-101983873 9:99221591-99221591
8 ALG2 NM_033087.4(ALG2):c.475A>G (p.Ile159Val)SNV Conflicting interpretations of pathogenicity 390397 rs146770430 9:101980992-101980992 9:99218710-99218710
9 ALG2 NM_033087.4(ALG2):c.159C>T (p.His53=)SNV Conflicting interpretations of pathogenicity 364213 rs527683080 9:101984018-101984018 9:99221736-99221736
10 ALG2 NM_033087.4(ALG2):c.1A>G (p.Met1Val)SNV Uncertain significance 364214 rs750172644 9:101984176-101984176 9:99221894-99221894
11 ALG2 NM_033087.4(ALG2):c.934C>T (p.Leu312Phe)SNV Uncertain significance 364206 rs147346291 9:101980533-101980533 9:99218251-99218251
12 ALG2 NM_033087.4(ALG2):c.472C>A (p.Pro158Thr)SNV Uncertain significance 364209 rs140382423 9:101980995-101980995 9:99218713-99218713
13 ALG2 NM_033087.4(ALG2):c.1132C>T (p.Arg378Cys)SNV Uncertain significance 265036 rs56393253 9:101980335-101980335 9:99218053-99218053
14 ALG2 NM_033087.4(ALG2):c.1174G>A (p.Ala392Thr)SNV Uncertain significance 364203 rs138258236 9:101980293-101980293 9:99218011-99218011
15 ALG2 NM_033087.4(ALG2):c.968G>T (p.Ser323Ile)SNV Uncertain significance 851540 9:101980499-101980499 9:99218217-99218217
16 ALG2 NM_033087.4(ALG2):c.239G>A (p.Gly80Asp)SNV Uncertain significance 862483 9:101983938-101983938 9:99221656-99221656
17 ALG2 NM_033087.4(ALG2):c.20G>A (p.Arg7Gln)SNV Uncertain significance 856875 9:101984157-101984157 9:99221875-99221875
18 ALG2 NM_033087.4(ALG2):c.1055_1056delinsTGA (p.Ser352fs)indel Uncertain significance 464893 rs1554707637 9:101980411-101980412 9:99218129-99218130
19 ALG2 NM_033087.4(ALG2):c.443A>G (p.Asp148Gly)SNV Uncertain significance 464896 rs369670496 9:101981024-101981024 9:99218742-99218742
20 ALG2 NM_033087.4(ALG2):c.44C>A (p.Pro15Gln)SNV Uncertain significance 464897 rs757920586 9:101984133-101984133 9:99221851-99221851
21 ALG2 NM_033087.4(ALG2):c.219C>G (p.Asp73Glu)SNV Uncertain significance 464894 rs755705607 9:101983958-101983958 9:99221676-99221676
22 ALG2 NM_033087.4(ALG2):c.10G>A (p.Glu4Lys)SNV Uncertain significance 533477 rs1329170357 9:101984167-101984167 9:99221885-99221885
23 ALG2 NM_033087.4(ALG2):c.399C>G (p.Ile133Met)SNV Uncertain significance 533478 rs371772900 9:101981068-101981068 9:99218786-99218786
24 ALG2 NM_033087.4(ALG2):c.92G>C (p.Arg31Pro)SNV Uncertain significance 533479 rs1279623882 9:101984085-101984085 9:99221803-99221803
25 ALG2 NM_033087.4(ALG2):c.449T>C (p.Phe150Ser)SNV Uncertain significance 575832 rs377047079 9:101981018-101981018 9:99218736-99218736
26 ALG2 NM_033087.4(ALG2):c.268G>T (p.Ala90Ser)SNV Uncertain significance 567442 rs941593352 9:101983909-101983909 9:99221627-99221627
27 ALG2 NM_033087.4(ALG2):c.236T>C (p.Leu79Pro)SNV Uncertain significance 568332 rs1564222174 9:101983941-101983941 9:99221659-99221659
28 ALG2 NM_033087.4(ALG2):c.678C>G (p.Phe226Leu)SNV Uncertain significance 579461 rs866855594 9:101980789-101980789 9:99218507-99218507
29 ALG2 NM_033087.4(ALG2):c.368T>C (p.Val123Ala)SNV Uncertain significance 575672 rs762560638 9:101981099-101981099 9:99218817-99218817
30 ALG2 NM_033087.4(ALG2):c.212C>T (p.Ala71Val)SNV Uncertain significance 578103 rs551744220 9:101983965-101983965 9:99221683-99221683
31 ALG2 NM_033087.4(ALG2):c.1177A>G (p.Arg393Gly)SNV Uncertain significance 566269 rs963221673 9:101980290-101980290 9:99218008-99218008
32 ALG2 NM_033087.4(ALG2):c.473C>T (p.Pro158Leu)SNV Uncertain significance 577856 rs746092484 9:101980994-101980994 9:99218712-99218712
33 ALG2 NM_033087.4(ALG2):c.319G>A (p.Glu107Lys)SNV Uncertain significance 638332 9:101983858-101983858 9:99221576-99221576
34 ALG2 NM_033087.4(ALG2):c.1030G>C (p.Val344Leu)SNV Uncertain significance 664201 9:101980437-101980437 9:99218155-99218155
35 ALG2 NM_033087.4(ALG2):c.784G>T (p.Val262Phe)SNV Uncertain significance 660985 9:101980683-101980683 9:99218401-99218401
36 ALG2 NM_033087.4(ALG2):c.446C>A (p.Ser149Tyr)SNV Uncertain significance 654848 9:101981021-101981021 9:99218739-99218739
37 ALG2 NM_033087.4(ALG2):c.386G>A (p.Arg129Gln)SNV Uncertain significance 662111 9:101981081-101981081 9:99218799-99218799
38 ALG2 NM_033087.4(ALG2):c.346C>G (p.Gln116Glu)SNV Uncertain significance 666047 9:101983831-101983831 9:99221549-99221549
39 ALG2 NM_033087.4(ALG2):c.314C>G (p.Ala105Gly)SNV Uncertain significance 654404 9:101983863-101983863 9:99221581-99221581
40 ALG2 NM_033087.4(ALG2):c.272A>C (p.Tyr91Ser)SNV Uncertain significance 648575 9:101983905-101983905 9:99221623-99221623
41 ALG2 NM_033087.4(ALG2):c.257_259CCG[3] (p.Ala87dup)short repeat Uncertain significance 647919 9:101983914-101983915 9:99221632-99221633
42 ALG2 NM_033087.4(ALG2):c.251_253GCG[3] (p.Gly85dup)short repeat Uncertain significance 647575 9:101983920-101983921 9:99221638-99221639
43 ALG2 NM_033087.4(ALG2):c.232G>C (p.Gly78Arg)SNV Uncertain significance 657644 9:101983945-101983945 9:99221663-99221663
44 ALG2 NM_033087.4(ALG2):c.182C>T (p.Ala61Val)SNV Uncertain significance 647355 9:101983995-101983995 9:99221713-99221713
45 ALG2 NM_033087.4(ALG2):c.97G>A (p.Val33Met)SNV Uncertain significance 663688 9:101984080-101984080 9:99221798-99221798
46 ALG2 NM_033087.4(ALG2):c.948G>A (p.Thr316=)SNV Likely benign 706183 9:101980519-101980519 9:99218237-99218237
47 ALG2 NM_033087.4(ALG2):c.813C>T (p.Asp271=)SNV Likely benign 705551 9:101980654-101980654 9:99218372-99218372
48 ALG2 NM_033087.4(ALG2):c.255C>G (p.Gly85=)SNV Likely benign 706900 9:101983922-101983922 9:99221640-99221640
49 ALG2 NM_033087.4(ALG2):c.1098G>A (p.Pro366=)SNV Likely benign 784859 9:101980369-101980369 9:99218087-99218087
50 ALG2 NM_033087.4(ALG2):c.462A>G (p.Leu154=)SNV Likely benign 747729 9:101981005-101981005 9:99218723-99218723

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

73
# Symbol AA change Variation ID SNP ID
1 ALG2 p.Val68Gly VAR_073332 rs730882051

Expression for Myasthenic Syndrome, Congenital, 14

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

Pathways for Myasthenic Syndrome, Congenital, 14

GO Terms for Myasthenic Syndrome, Congenital, 14

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

# Name GO ID Score Top Affiliating Genes
1 skeletal muscle contraction GO:0003009 9.32 CHRNB1 CCDC78
2 lipoprotein metabolic process GO:0042157 9.26 APOL4 APOL2
3 regulation of long-term neuronal synaptic plasticity GO:0048169 9.16 KRAS HRAS
4 dolichol-linked oligosaccharide biosynthetic process GO:0006488 8.96 ALG2 ALG14
5 response to isolation stress GO:0035900 8.62 KRAS HRAS

Sources for Myasthenic Syndrome, Congenital, 14

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
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32 ICD10
33 ICD10 via Orphanet
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35 IUPHAR
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39 LOVD
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43 MeSH
44 MESH via Orphanet
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48 NCI
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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
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72 UMLS via Orphanet
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