CMS14
MCID: MYS078
MIFTS: 40

Myasthenic Syndrome, Congenital, 14 (CMS14)

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

Aliases & Classifications for Myasthenic Syndrome, Congenital, 14

MalaCards integrated aliases for Myasthenic Syndrome, Congenital, 14:

Name: Myasthenic Syndrome, Congenital, 14 57 73 29 6
Myasthenic Syndrome, Congenital, 14, with Tubular Aggregates 57 73 29
Cmsta3 57 12 73
Cms14 57 12 73
Myasthenic Syndrome, Congenital, with Tubular Aggregates 3 57 71
Congenital Myasthenic Syndrome 14 12 15
Myasthenic Syndrome, Congenital, with Tubular Aggregates 3; Cmsta3 57
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®:

57 (Updated 05-Mar-2021)
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 muscular dystrophy-dystroglycanopathy a14 and hepatic flexure cancer, 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 high palate

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) (Updated 05-Mar-2021)

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 60)
# Related Disease Score Top Affiliating Genes
1 congenital muscular dystrophy-dystroglycanopathy a14 10.3 CCDC78 ALG14
2 hepatic flexure cancer 10.3 KRAS HRAS
3 trachea carcinoma in situ 10.3 KRAS HRAS
4 signet ring basal cell carcinoma 10.3 KRAS HRAS
5 cobblestone retinal degeneration 10.3 KRAS HRAS
6 immature teratoma of ovary 10.3 KRAS HRAS
7 descending colon cancer 10.3 KRAS HRAS
8 ampulla of vater neoplasm 10.3 KRAS HRAS
9 transverse colon cancer 10.2 KRAS HRAS
10 periampullary adenoma 10.2 KRAS HRAS
11 acneiform dermatitis 10.2 KRAS HRAS
12 appendiceal neoplasm 10.2 KRAS HRAS
13 gallbladder benign neoplasm 10.2 KRAS HRAS
14 adenosquamous lung carcinoma 10.2 KRAS HRAS
15 appendix adenocarcinoma 10.2 KRAS HRAS
16 mucinous lung adenocarcinoma 10.2 KRAS HRAS
17 wolffian duct adenocarcinoma 10.2 KRAS HRAS
18 myh-associated polyposis 10.2 KRAS HRAS
19 noonan syndrome-like disorder with loose anagen hair 1 10.2 KRAS HRAS
20 noonan syndrome-like disorder with loose anagen hair 10.2 KRAS HRAS
21 ascending colon cancer 10.2 KRAS HRAS
22 biliary tract benign neoplasm 10.2 KRAS HRAS
23 ovarian mucinous neoplasm 10.2 KRAS HRAS
24 malignant exocrine pancreas neoplasm 10.2 KRAS HRAS
25 pancreatic acinar cell adenocarcinoma 10.2 KRAS HRAS
26 paronychia 10.2 KRAS HRAS
27 appendix disease 10.2 KRAS HRAS
28 bile duct cysts 10.2 KRAS HRAS
29 lung carcinoma in situ 10.2 KRAS HRAS
30 small intestine adenocarcinoma 10.2 KRAS HRAS
31 papillary adenoma 10.2 KRAS HRAS
32 ethmoid sinus adenocarcinoma 10.2 KRAS HRAS
33 appendix cancer 10.2 KRAS HRAS
34 duodenum adenocarcinoma 10.2 KRAS HRAS
35 core binding factor acute myeloid leukemia 10.2 KRAS HRAS
36 pulmonary adenocarcinoma in situ 10.2 KRAS HRAS
37 oculoectodermal syndrome 10.2 KRAS HRAS
38 large intestine adenocarcinoma 10.2 KRAS HRAS
39 fructose intolerance, hereditary 10.2 ALG2 ALG14
40 nasal cavity adenocarcinoma 10.2 KRAS HRAS
41 spinocerebellar ataxia, autosomal recessive 10 10.1 MYO9A ALG14
42 eccrine papillary adenoma 10.1 KRAS HRAS
43 rectosigmoid cancer 10.1 KRAS HRAS
44 lung non-squamous non-small cell carcinoma 10.1 KRAS HRAS
45 female reproductive endometrioid cancer 10.1 KRAS HRAS
46 anus cancer 10.1 KRAS HRAS
47 duodenum cancer 10.0 KRAS HRAS
48 duodenum disease 10.0 KRAS HRAS
49 skin papilloma 10.0 KRAS HRAS
50 slow-channel congenital myasthenic syndrome 9.8 CHRND CHRNB1

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 high palate 31 occasional (7.5%) HP:0000218
3 hyperlordosis 31 occasional (7.5%) HP:0003307
4 pes planus 31 occasional (7.5%) HP:0001763
5 flexion contracture 31 occasional (7.5%) HP:0001371
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 mildly elevated creatine kinase 31 occasional (7.5%) HP:0008180
10 generalized hypotonia 31 occasional (7.5%) HP:0001290
11 distal joint laxity 31 occasional (7.5%) HP:0020152
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®:

57 (Updated 05-Mar-2021)
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 (Updated 05-Mar-2021)

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 57
24461433 2014
2
Congenital myasthenic syndromes due to mutations in ALG2 and ALG14. 57 6
23404334 2013

Variations for Myasthenic Syndrome, Congenital, 14

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

6 (show top 50) (show all 83)
# 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.215_225del (p.Gly72fs) Deletion Pathogenic 992273 9:101983952-101983962 9:99221670-99221680
4 ALG2 NM_033087.4(ALG2):c.1040del (p.Gly347fs) Deletion Likely pathogenic 2699 rs387906281 9:101980427-101980427 9:99218145-99218145
5 ALG2 NM_033087.4(ALG2):c.475A>G (p.Ile159Val) SNV Conflicting interpretations of pathogenicity 390397 rs146770430 9:101980992-101980992 9:99218710-99218710
6 ALG2 NM_033087.4(ALG2):c.319G>A (p.Glu107Lys) SNV Uncertain significance 638332 rs1156439417 9:101983858-101983858 9:99221576-99221576
7 ALG2 NM_033087.4(ALG2):c.472C>A (p.Pro158Thr) SNV Uncertain significance 364209 rs140382423 9:101980995-101980995 9:99218713-99218713
8 ALG2 NM_033087.4(ALG2):c.182C>T (p.Ala61Val) SNV Uncertain significance 647355 rs1588620643 9:101983995-101983995 9:99221713-99221713
9 ALG2 NM_033087.4(ALG2):c.251_253GCG[3] (p.Gly85dup) Microsatellite Uncertain significance 647575 rs1050763044 9:101983920-101983921 9:99221638-99221639
10 ALG2 NM_033087.4(ALG2):c.257_259CCG[3] (p.Ala87dup) Microsatellite Uncertain significance 647919 rs759891618 9:101983914-101983915 9:99221632-99221633
11 ALG2 NM_033087.4(ALG2):c.272A>C (p.Tyr91Ser) SNV Uncertain significance 648575 rs910168958 9:101983905-101983905 9:99221623-99221623
12 ALG2 NM_033087.4(ALG2):c.314C>G (p.Ala105Gly) SNV Uncertain significance 654404 rs747781559 9:101983863-101983863 9:99221581-99221581
13 ALG2 NM_033087.4(ALG2):c.446C>A (p.Ser149Tyr) SNV Uncertain significance 654848 rs1350412580 9:101981021-101981021 9:99218739-99218739
14 ALG2 NM_033087.4(ALG2):c.232G>C (p.Gly78Arg) SNV Uncertain significance 657644 rs1054683823 9:101983945-101983945 9:99221663-99221663
15 ALG2 NM_033087.4(ALG2):c.784G>T (p.Val262Phe) SNV Uncertain significance 660985 rs1229029511 9:101980683-101980683 9:99218401-99218401
16 ALG2 NM_033087.4(ALG2):c.386G>A (p.Arg129Gln) SNV Uncertain significance 662111 rs1025210566 9:101981081-101981081 9:99218799-99218799
17 ALG2 NM_033087.4(ALG2):c.97G>A (p.Val33Met) SNV Uncertain significance 663688 rs774607653 9:101984080-101984080 9:99221798-99221798
18 ALG2 NM_033087.4(ALG2):c.1030G>C (p.Val344Leu) SNV Uncertain significance 664201 rs1588618702 9:101980437-101980437 9:99218155-99218155
19 ALG2 NM_033087.4(ALG2):c.346C>G (p.Gln116Glu) SNV Uncertain significance 666047 rs754476664 9:101983831-101983831 9:99221549-99221549
20 ALG2 NM_033087.4(ALG2):c.219C>G (p.Asp73Glu) SNV Uncertain significance 464894 rs755705607 9:101983958-101983958 9:99221676-99221676
21 ALG2 NM_033087.4(ALG2):c.1132C>T (p.Arg378Cys) SNV Uncertain significance 265036 rs56393253 9:101980335-101980335 9:99218053-99218053
22 ALG2 NM_033087.4(ALG2):c.443A>G (p.Asp148Gly) SNV Uncertain significance 464896 rs369670496 9:101981024-101981024 9:99218742-99218742
23 ALG2 NM_033087.4(ALG2):c.1174G>A (p.Ala392Thr) SNV Uncertain significance 364203 rs138258236 9:101980293-101980293 9:99218011-99218011
24 ALG2 NM_033087.4(ALG2):c.44C>A (p.Pro15Gln) SNV Uncertain significance 464897 rs757920586 9:101984133-101984133 9:99221851-99221851
25 ALG2 NM_033087.4(ALG2):c.1055_1056delinsTGA (p.Ser352fs) Indel Uncertain significance 464893 rs1554707637 9:101980411-101980412 9:99218129-99218130
26 ALG2 NM_033087.4(ALG2):c.10G>A (p.Glu4Lys) SNV Uncertain significance 533477 rs1329170357 9:101984167-101984167 9:99221885-99221885
27 ALG2 NM_033087.4(ALG2):c.399C>G (p.Ile133Met) SNV Uncertain significance 533478 rs371772900 9:101981068-101981068 9:99218786-99218786
28 ALG2 NM_033087.4(ALG2):c.92G>C (p.Arg31Pro) SNV Uncertain significance 533479 rs1279623882 9:101984085-101984085 9:99221803-99221803
29 ALG2 NM_033087.4(ALG2):c.20G>A (p.Arg7Gln) SNV Uncertain significance 856875 9:101984157-101984157 9:99221875-99221875
30 ALG2 NM_033087.4(ALG2):c.934C>T (p.Leu312Phe) SNV Uncertain significance 364206 rs147346291 9:101980533-101980533 9:99218251-99218251
31 ALG2 NM_033087.4(ALG2):c.239G>A (p.Gly80Asp) SNV Uncertain significance 862483 9:101983938-101983938 9:99221656-99221656
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.212C>T (p.Ala71Val) SNV Uncertain significance 578103 rs551744220 9:101983965-101983965 9:99221683-99221683
34 ALG2 NM_033087.4(ALG2):c.678C>G (p.Phe226Leu) SNV Uncertain significance 579461 rs866855594 9:101980789-101980789 9:99218507-99218507
35 ALG2 NM_033087.4(ALG2):c.1A>G (p.Met1Val) SNV Uncertain significance 364214 rs750172644 9:101984176-101984176 9:99221894-99221894
36 ALG2 NM_033087.4(ALG2):c.1177A>G (p.Arg393Gly) SNV Uncertain significance 566269 rs963221673 9:101980290-101980290 9:99218008-99218008
37 ALG2 NM_033087.4(ALG2):c.268G>T (p.Ala90Ser) SNV Uncertain significance 567442 rs941593352 9:101983909-101983909 9:99221627-99221627
38 ALG2 NM_033087.4(ALG2):c.236T>C (p.Leu79Pro) SNV Uncertain significance 568332 rs1564222174 9:101983941-101983941 9:99221659-99221659
39 ALG2 NM_033087.4(ALG2):c.368T>C (p.Val123Ala) SNV Uncertain significance 575672 rs762560638 9:101981099-101981099 9:99218817-99218817
40 ALG2 NM_033087.4(ALG2):c.449T>C (p.Phe150Ser) SNV Uncertain significance 575832 rs377047079 9:101981018-101981018 9:99218736-99218736
41 ALG2 NM_033087.4(ALG2):c.629C>G (p.Ser210Ter) SNV Uncertain significance 934052 9:101980838-101980838 9:99218556-99218556
42 ALG2 NM_033087.4(ALG2):c.516C>A (p.Cys172Ter) SNV Uncertain significance 936226 9:101980951-101980951 9:99218669-99218669
43 ALG2 NM_033087.4(ALG2):c.686T>A (p.Leu229His) SNV Uncertain significance 938218 9:101980781-101980781 9:99218499-99218499
44 ALG2 NM_033087.4(ALG2):c.1095C>G (p.Asp365Glu) SNV Uncertain significance 940868 9:101980372-101980372 9:99218090-99218090
45 ALG2 NM_033087.4(ALG2):c.519C>G (p.Ile173Met) SNV Uncertain significance 941257 9:101980948-101980948 9:99218666-99218666
46 ALG2 NM_033087.4(ALG2):c.215G>T (p.Gly72Val) SNV Uncertain significance 941497 9:101983962-101983962 9:99221680-99221680
47 ALG2 NM_033087.4(ALG2):c.760T>G (p.Leu254Val) SNV Uncertain significance 941824 9:101980707-101980707 9:99218425-99218425
48 ALG2 NM_033087.4(ALG2):c.212C>G (p.Ala71Gly) SNV Uncertain significance 917751 9:101983965-101983965 9:99221683-99221683
49 ALG2 NM_033087.4(ALG2):c.299A>G (p.Tyr100Cys) SNV Uncertain significance 946667 9:101983878-101983878 9:99221596-99221596
50 ALG2 NM_033087.4(ALG2):c.1150G>A (p.Ala384Thr) SNV Uncertain significance 947697 9:101980317-101980317 9:99218035-99218035

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

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

# Name GO ID Score Top Affiliating Genes
1 integral component of postsynaptic specialization membrane GO:0099060 8.96 CHRND CHRNB1
2 acetylcholine-gated channel complex GO:0005892 8.62 CHRND CHRNB1

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

# Name GO ID Score Top Affiliating Genes
1 lipoprotein metabolic process GO:0042157 9.37 APOL4 APOL2
2 muscle contraction GO:0006936 9.33 MYBPC1 CHRND CHRNB1
3 regulation of long-term neuronal synaptic plasticity GO:0048169 9.32 KRAS HRAS
4 dolichol-linked oligosaccharide biosynthetic process GO:0006488 9.26 ALG2 ALG14
5 response to isolation stress GO:0035900 8.96 KRAS HRAS
6 skeletal muscle contraction GO:0003009 8.8 CHRND CHRNB1 CCDC78

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

# Name GO ID Score Top Affiliating Genes
1 acetylcholine-gated cation-selective channel activity GO:0022848 8.96 CHRND CHRNB1
2 acetylcholine binding GO:0042166 8.62 CHRND CHRNB1

Sources for Myasthenic Syndrome, Congenital, 14

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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