CMS16
MCID: MYS064
MIFTS: 33

Myasthenic Syndrome, Congenital, 16 (CMS16)

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

Aliases & Classifications for Myasthenic Syndrome, Congenital, 16

MalaCards integrated aliases for Myasthenic Syndrome, Congenital, 16:

Name: Myasthenic Syndrome, Congenital, 16 57 72
Cms16 57 12 72
Myasthenic Syndrome, Congenital, Acetazolamide-Responsive 57 72
Congenital Myasthenic Syndrome, Acetazolamide-Responsive 29 6
Congenital Myasthenic Syndrome 16 12 15
Congenital Myasthenic Syndrome Acetazolamide-Responsive 12
Congenital Myasthenic Syndrome Due to Mutation in Scn4a 72
Congenital Myasthenic Syndrome Scn4a-Related 72

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
variable severity
two unrelated patients have been reported (last curated october 2015)


HPO:

31
myasthenic syndrome, congenital, 16:
Inheritance autosomal recessive inheritance
Onset and clinical course variable expressivity infantile onset


Classifications:



External Ids:

Disease Ontology 12 DOID:0110682
OMIM® 57 614198
OMIM Phenotypic Series 57 PS601462
MeSH 44 D020294
MedGen 41 C3280112

Summaries for Myasthenic Syndrome, Congenital, 16

UniProtKB/Swiss-Prot : 72 Myasthenic syndrome, congenital, 16: 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. CMS16 is characterized by fatigable generalized weakness and recurrent attacks of respiratory and bulbar paralysis since birth. The fatigable weakness involves lid-elevator, external ocular, facial, limb and truncal muscles and an decremental response of the compound muscle action potential on repetitive stimulation.

MalaCards based summary : Myasthenic Syndrome, Congenital, 16, also known as cms16, is related to periodic paralyses and normokalemic periodic paralysis. An important gene associated with Myasthenic Syndrome, Congenital, 16 is SCN4A (Sodium Voltage-Gated Channel Alpha Subunit 4). Related phenotypes are high palate and hyperlordosis

Disease Ontology : 12 A congenital myasthenic syndrome that has material basis in heterozygous or homozygous mutation in the SCN4A gene on chromosome 17q23.

OMIM® : 57 Congenital myasthenic syndrome is a disorder characterized by variable degrees of muscle fatigability caused by impaired transmission of electrical signals at the neuromuscular junction (NMJ) (summary by Arnold et al., 2015). For a discussion of genetic heterogeneity of CMS, see CMS1A (601462). (614198) (Updated 05-Apr-2021)

Related Diseases for Myasthenic Syndrome, Congenital, 16

Graphical network of the top 20 diseases related to Myasthenic Syndrome, Congenital, 16:



Diseases related to Myasthenic Syndrome, Congenital, 16

Symptoms & Phenotypes for Myasthenic Syndrome, Congenital, 16

Human phenotypes related to Myasthenic Syndrome, Congenital, 16:

31 (show all 9)
# Description HPO Frequency HPO Source Accession
1 high palate 31 occasional (7.5%) HP:0000218
2 hyperlordosis 31 occasional (7.5%) HP:0003307
3 apnea 31 occasional (7.5%) HP:0002104
4 ptosis 31 HP:0000508
5 gait disturbance 31 HP:0001288
6 motor delay 31 HP:0001270
7 easy fatigability 31 HP:0003388
8 external ophthalmoplegia 31 HP:0000544
9 fatigable weakness 31 HP:0003473

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Head And Neck Eyes:
ptosis
external ophthalmoplegia

Neurologic Central Nervous System:
delayed motor development

Respiratory:
apneic episodes (1 patient)

Laboratory Abnormalities:
normal potassium levels

Muscle Soft Tissue:
easy fatigability
impaired gait
muscle weakness, episodic
weakness worsened by activity
decremental compound muscle action potential on repetitive stimulation

Head And Neck Mouth:
high-arched palate (1 patient)

Skeletal Spine:
lordosis (1 patient)

Clinical features from OMIM®:

614198 (Updated 05-Apr-2021)

Drugs & Therapeutics for Myasthenic Syndrome, Congenital, 16

Search Clinical Trials , NIH Clinical Center for Myasthenic Syndrome, Congenital, 16

Genetic Tests for Myasthenic Syndrome, Congenital, 16

Genetic tests related to Myasthenic Syndrome, Congenital, 16:

# Genetic test Affiliating Genes
1 Congenital Myasthenic Syndrome, Acetazolamide-Responsive 29 SCN4A

Anatomical Context for Myasthenic Syndrome, Congenital, 16

Publications for Myasthenic Syndrome, Congenital, 16

Articles related to Myasthenic Syndrome, Congenital, 16:

# Title Authors PMID Year
1
Defective fast inactivation recovery of Nav 1.4 in congenital myasthenic syndrome. 6 57
25707578 2015
2
Myasthenic syndrome caused by mutation of the SCN4A sodium channel. 57 6
12766226 2003

Variations for Myasthenic Syndrome, Congenital, 16

ClinVar genetic disease variations for Myasthenic Syndrome, Congenital, 16:

6 (show top 50) (show all 241)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 GH-LCR , SCN4A NM_000334.4(SCN4A):c.3625T>C (p.Cys1209Arg) SNV Pathogenic 807677 rs1598406692 GRCh37: 17:62022815-62022815
GRCh38: 17:63945455-63945455
2 SCN4A NM_000334.4(SCN4A):c.1201C>T (p.Arg401Cys) SNV Pathogenic 807678 rs1188070167 GRCh37: 17:62043503-62043503
GRCh38: 17:63966143-63966143
3 GH-LCR , SCN4A NM_000334.4(SCN4A):c.3938C>T (p.Thr1313Met) SNV Pathogenic 5904 rs121908547 GRCh37: 17:62021185-62021185
GRCh38: 17:63943825-63943825
4 SCN4A NM_000334.4(SCN4A):c.1333G>A (p.Val445Met) SNV Pathogenic 5910 rs121908552 GRCh37: 17:62041947-62041947
GRCh38: 17:63964587-63964587
5 GH-LCR , SCN4A NM_000334.4(SCN4A):c.4370G>A (p.Arg1457His) SNV Pathogenic 217263 rs863225046 GRCh37: 17:62019272-62019272
GRCh38: 17:63941912-63941912
6 GH-LCR , SCN4A NM_000334.4(SCN4A):c.4774A>G (p.Met1592Val) SNV Pathogenic 5897 rs80338962 GRCh37: 17:62018868-62018868
GRCh38: 17:63941508-63941508
7 GH-LCR , SCN4A NM_000334.4(SCN4A):c.2111C>T (p.Thr704Met) SNV Pathogenic 5896 rs80338957 GRCh37: 17:62034787-62034787
GRCh38: 17:63957427-63957427
8 GH-LCR , SCN4A NM_000334.4(SCN4A):c.4325T>A (p.Val1442Glu) SNV Pathogenic 5914 rs121908553 GRCh37: 17:62019317-62019317
GRCh38: 17:63941957-63941957
9 SCN4A NM_000334.4(SCN4A):c.737C>T (p.Ser246Leu) SNV Pathogenic 21161 rs80338951 GRCh37: 17:62045682-62045682
GRCh38: 17:63968322-63968322
10 SCN4A NM_000334.4(SCN4A):c.685del (p.Thr229fs) Deletion Pathogenic 1032988 GRCh37: 17:62048540-62048540
GRCh38: 17:63971180-63971180
11 SCN4A NM_000334.4(SCN4A):c.664C>T (p.Arg222Trp) SNV Likely pathogenic 143199 rs527236148 GRCh37: 17:62048561-62048561
GRCh38: 17:63971201-63971201
12 GH-LCR , SCN4A NM_000334.4(SCN4A):c.4776G>A (p.Met1592Ile) SNV Likely pathogenic 427072 rs886041805 GRCh37: 17:62018866-62018866
GRCh38: 17:63941506-63941506
13 SCN4A NM_000334.4(SCN4A):c.154C>T (p.Arg52Trp) SNV Uncertain significance 477399 rs201379704 GRCh37: 17:62050048-62050048
GRCh38: 17:63972688-63972688
14 SCN4A NM_000334.4(SCN4A):c.1011T>C (p.Asp337=) SNV Uncertain significance 324548 rs372791798 GRCh37: 17:62045408-62045408
GRCh38: 17:63968048-63968048
15 SCN4A NM_000334.4(SCN4A):c.1413G>A (p.Met471Ile) SNV Uncertain significance 324542 rs527384137 GRCh37: 17:62041867-62041867
GRCh38: 17:63964507-63964507
16 SCN4A NM_000334.4(SCN4A):c.1018G>A (p.Ala340Thr) SNV Uncertain significance 429845 rs147936148 GRCh37: 17:62045401-62045401
GRCh38: 17:63968041-63968041
17 SCN4A NM_000334.4(SCN4A):c.82A>C (p.Ile28Leu) SNV Uncertain significance 324554 rs886053250 GRCh37: 17:62050120-62050120
GRCh38: 17:63972760-63972760
18 SCN4A NM_000334.4(SCN4A):c.1462G>A (p.Ala488Thr) SNV Uncertain significance 324540 rs185941768 GRCh37: 17:62041176-62041176
GRCh38: 17:63963816-63963816
19 GH-LCR , SCN4A NM_000334.4(SCN4A):c.5205G>C (p.Gln1735His) SNV Uncertain significance 324510 rs199944673 GRCh37: 17:62018437-62018437
GRCh38: 17:63941077-63941077
20 GH-LCR , SCN4A NM_000334.4(SCN4A):c.2704G>A (p.Gly902Ser) SNV Uncertain significance 543804 rs200517944 GRCh37: 17:62028933-62028933
GRCh38: 17:63951573-63951573
21 GH-LCR , SCN4A NM_000334.4(SCN4A):c.2704G>A (p.Gly902Ser) SNV Uncertain significance 543804 rs200517944 GRCh37: 17:62028933-62028933
GRCh38: 17:63951573-63951573
22 SCN4A NM_000334.4(SCN4A):c.1018G>A (p.Ala340Thr) SNV Uncertain significance 429845 rs147936148 GRCh37: 17:62045401-62045401
GRCh38: 17:63968041-63968041
23 GH-LCR , SCN4A NM_000334.4(SCN4A):c.2778C>T (p.Ile926=) SNV Uncertain significance 673965 rs769634298 GRCh37: 17:62028859-62028859
GRCh38: 17:63951499-63951499
24 SCN4A NM_000334.4(SCN4A):c.999C>T (p.Asn333=) SNV Uncertain significance 448288 rs149726115 GRCh37: 17:62045420-62045420
GRCh38: 17:63968060-63968060
25 GH-LCR , SCN4A NM_000334.4(SCN4A):c.2890G>A (p.Val964Ile) SNV Uncertain significance 432019 rs200947169 GRCh37: 17:62026852-62026852
GRCh38: 17:63949492-63949492
26 GH-LCR , SCN4A NM_000334.4(SCN4A):c.3429C>T (p.Phe1143=) SNV Uncertain significance 255848 rs373597946 GRCh37: 17:62024417-62024417
GRCh38: 17:63947057-63947057
27 GH-LCR , SCN4A NM_000334.4(SCN4A):c.2623C>T (p.Pro875Ser) SNV Uncertain significance 324531 rs201148948 GRCh37: 17:62029014-62029014
GRCh38: 17:63951654-63951654
28 SCN4A NM_000334.4(SCN4A):c.403A>C (p.Met135Leu) SNV Uncertain significance 255852 rs148028364 GRCh37: 17:62049575-62049575
GRCh38: 17:63972215-63972215
29 SCN4A NM_000334.4(SCN4A):c.952T>C (p.Trp318Arg) SNV Uncertain significance 252477 rs199676994 GRCh37: 17:62045467-62045467
GRCh38: 17:63968107-63968107
30 SCN4A NM_000334.4(SCN4A):c.1100+7G>A SNV Uncertain significance 255842 rs200770684 GRCh37: 17:62043834-62043834
GRCh38: 17:63966474-63966474
31 GH-LCR , SCN4A NM_000334.4(SCN4A):c.2854-5C>T SNV Uncertain significance 324527 rs374039266 GRCh37: 17:62026893-62026893
GRCh38: 17:63949533-63949533
32 GH-LCR , SCN4A NM_000334.4(SCN4A):c.3386G>A (p.Arg1129Gln) SNV Uncertain significance 143200 rs527236149 GRCh37: 17:62024460-62024460
GRCh38: 17:63947100-63947100
33 GH-LCR , SCN4A NM_000334.4(SCN4A):c.2794G>A (p.Asp932Asn) SNV Uncertain significance 477408 rs199656266 GRCh37: 17:62028843-62028843
GRCh38: 17:63951483-63951483
34 SCN4A NM_000334.4(SCN4A):c.1575C>T (p.Ser525=) SNV Uncertain significance 890240 GRCh37: 17:62041063-62041063
GRCh38: 17:63963703-63963703
35 GH-LCR , SCN4A NM_000334.4(SCN4A):c.5181G>A (p.Glu1727=) SNV Uncertain significance 477426 rs368263333 GRCh37: 17:62018461-62018461
GRCh38: 17:63941101-63941101
36 GH-LCR , SCN4A NM_000334.4(SCN4A):c.4083C>A (p.Ile1361=) SNV Uncertain significance 705783 rs374480468 GRCh37: 17:62020391-62020391
GRCh38: 17:63943031-63943031
37 SCN4A NM_000334.4(SCN4A):c.205G>A (p.Gly69Arg) SNV Uncertain significance 324553 rs886053249 GRCh37: 17:62049997-62049997
GRCh38: 17:63972637-63972637
38 SCN4A NM_000334.4(SCN4A):c.364C>T (p.Arg122Cys) SNV Uncertain significance 324551 rs150158100 GRCh37: 17:62049740-62049740
GRCh38: 17:63972380-63972380
39 SCN4A NM_000334.4(SCN4A):c.483-9C>A SNV Uncertain significance 255857 rs201552497 GRCh37: 17:62049219-62049219
GRCh38: 17:63971859-63971859
40 GH-LCR , SCN4A NM_000334.4(SCN4A):c.2563A>G (p.Met855Val) SNV Uncertain significance 324534 rs372019457 GRCh37: 17:62029074-62029074
GRCh38: 17:63951714-63951714
41 GH-LCR , SCN4A NM_000334.4(SCN4A):c.4215C>T (p.Leu1405=) SNV Uncertain significance 255854 rs141215137 GRCh37: 17:62020259-62020259
GRCh38: 17:63942899-63942899
42 GH-LCR , SCN4A NM_000334.4(SCN4A):c.4048G>A (p.Val1350Met) SNV Uncertain significance 652081 rs200274258 GRCh37: 17:62020426-62020426
GRCh38: 17:63943066-63943066
43 SCN4A NM_000334.4(SCN4A):c.95C>A (p.Ala32Glu) SNV Uncertain significance 860459 GRCh37: 17:62050107-62050107
GRCh38: 17:63972747-63972747
44 SCN4A NM_000334.4(SCN4A):c.553G>A (p.Asp185Asn) SNV Uncertain significance 197134 rs778661227 GRCh37: 17:62049140-62049140
GRCh38: 17:63971780-63971780
45 GH-LCR , SCN4A NM_000334.4(SCN4A):c.3136G>T (p.Gly1046Trp) SNV Uncertain significance 324524 rs759982229 GRCh37: 17:62025979-62025979
GRCh38: 17:63948619-63948619
46 GH-LCR , SCN4A NM_000334.4(SCN4A):c.4667A>G (p.Asn1556Ser) SNV Uncertain significance 324516 rs751454852 GRCh37: 17:62018975-62018975
GRCh38: 17:63941615-63941615
47 GH-LCR , SCN4A NM_000334.4(SCN4A):c.4609G>A (p.Gly1537Ser) SNV Uncertain significance 222028 rs571210585 GRCh37: 17:62019033-62019033
GRCh38: 17:63941673-63941673
48 GH-LCR , SCN4A NM_000334.4(SCN4A):c.5401G>A (p.Ala1801Thr) SNV Uncertain significance 646984 rs201192904 GRCh37: 17:62018241-62018241
GRCh38: 17:63940881-63940881
49 GH-LCR , SCN4A NM_000334.4(SCN4A):c.5000C>T (p.Pro1667Leu) SNV Uncertain significance 808307 rs765721076 GRCh37: 17:62018642-62018642
GRCh38: 17:63941282-63941282
50 SCN4A NM_000334.4(SCN4A):c.1653C>T (p.Cys551=) SNV Uncertain significance 324538 rs201199086 GRCh37: 17:62038745-62038745
GRCh38: 17:63961385-63961385

UniProtKB/Swiss-Prot genetic disease variations for Myasthenic Syndrome, Congenital, 16:

72
# Symbol AA change Variation ID SNP ID
1 SCN4A p.Val1442Glu VAR_017795 rs121908553
2 SCN4A p.Arg1454Trp VAR_075436 rs879253789
3 SCN4A p.Arg1457His VAR_075437 rs863225046

Expression for Myasthenic Syndrome, Congenital, 16

Search GEO for disease gene expression data for Myasthenic Syndrome, Congenital, 16.

Pathways for Myasthenic Syndrome, Congenital, 16

GO Terms for Myasthenic Syndrome, Congenital, 16

Cellular components related to Myasthenic Syndrome, Congenital, 16 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 axon cytoplasm GO:1904115 8.96 KIF5C KIF3B
2 kinesin complex GO:0005871 8.62 KIF5C KIF3B

Biological processes related to Myasthenic Syndrome, Congenital, 16 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 microtubule-based movement GO:0007018 8.62 KIF5C KIF3B

Molecular functions related to Myasthenic Syndrome, Congenital, 16 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 microtubule motor activity GO:0003777 8.96 KIF5C KIF3B
2 ATP-dependent microtubule motor activity, plus-end-directed GO:0008574 8.62 KIF5C KIF3B

Sources for Myasthenic Syndrome, Congenital, 16

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-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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