CMS4A
MCID: MYS059
MIFTS: 25

Myasthenic Syndrome, Congenital, 4a, Slow-Channel (CMS4A)

Categories: Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Myasthenic Syndrome, Congenital, 4a, Slow-Channel

MalaCards integrated aliases for Myasthenic Syndrome, Congenital, 4a, Slow-Channel:

Name: Myasthenic Syndrome, Congenital, 4a, Slow-Channel 57 75 29 6
Myasthenia, Familial Infantile, 1 75 13 73
Cms4a 57 12 75
Cms Ia1 12 75
Cms1a1 12 75
Congenital Myasthenic Syndrome Type Ia1, Formerly; Cms1a1, Formerly 57
Myasthenic Syndrome, Congenital, Type 4a, Slow-Channel 40
Congenital Myasthenic Syndrome Type Ia1, Formerly 57
Congenital Myasthenic Syndrome 4a Slow-Channel 12
Congenital Myasthenic Syndrome Type Ia1 75
Congenital Myasthenic Syndrometype Ia1 12
Congenital Myasthenic Syndrome 4a 12
Cms Ia1, Formerly 57
Cms1a1, Formerly 57

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant
autosomal recessive (rare)

Miscellaneous:
poor response to acetylcholinesterase inhibitors
variable age at onset (range infancy to young adult)
most cases are autosomal dominant, recessive inheritance has rarely been reported


HPO:

32
myasthenic syndrome, congenital, 4a, slow-channel:
Onset and clinical course congenital onset
Inheritance autosomal recessive inheritance autosomal dominant inheritance


Classifications:



Summaries for Myasthenic Syndrome, Congenital, 4a, Slow-Channel

UniProtKB/Swiss-Prot : 75 Myasthenic syndrome, congenital, 4A, slow-channel: 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 affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS4A is a slow-channel myasthenic syndrome. It is caused by kinetic abnormalities of the AChR, resulting in prolonged AChR channel opening episodes, prolonged endplate currents, and depolarization block. This is associated with calcium overload, which may contribute to subsequent degeneration of the endplate and postsynaptic membrane.

MalaCards based summary : Myasthenic Syndrome, Congenital, 4a, Slow-Channel, also known as myasthenia, familial infantile, 1, is related to congenital myasthenic syndrome and myasthenic syndrome, congenital, 4c, associated with acetylcholine receptor deficiency. An important gene associated with Myasthenic Syndrome, Congenital, 4a, Slow-Channel is CHRNE (Cholinergic Receptor Nicotinic Epsilon Subunit). Related phenotypes are ptosis and dysphagia

Disease Ontology : 12 A congenital myasthenic syndrome characterized by postsynaptic neuromuscular junction defects, early-onset progressive muscle weakness, and prolonged opening and activity of the acetylcholine receptor channel that has material basis in heterozygous or rarely biallelic mutation in the CHRNE gene on chromosome 17p13.

OMIM : 57 Slow-channel congenital myasthenic syndrome (SCCMS) is a disorder of the postsynaptic neuromuscular junction (NMJ) characterized by early-onset progressive muscle weakness. The disorder results from kinetic abnormalities of the acetylcholine receptor channel, specifically from prolonged opening and activity of the channel, which causes prolonged synaptic currents resulting in a depolarization block. This is associated with calcium overload, which may contribute to subsequent degeneration of the endplate and postsynaptic membrane. Treatment with quinine, quinidine, or fluoxetine may be helpful; acetylcholinesterase inhibitors and amifampridine should be avoided (summary by Engel et al., 2015). For a discussion of genetic heterogeneity of CMS, see CMS1A (601462). (605809)

Related Diseases for Myasthenic Syndrome, Congenital, 4a, Slow-Channel

Diseases in the Slow-Channel Congenital Myasthenic Syndrome family:

Myasthenic Syndrome, Congenital, 1a, Slow-Channel Myasthenic Syndrome, Congenital, 4a, Slow-Channel
Myasthenic Syndrome, Congenital, 2a, Slow-Channel Myasthenic Syndrome, Congenital, 3a, Slow-Channel

Diseases related to Myasthenic Syndrome, Congenital, 4a, Slow-Channel via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 congenital myasthenic syndrome 31.2 C17orf107 CHRNE
2 myasthenic syndrome, congenital, 4c, associated with acetylcholine receptor deficiency 11.5
3 myasthenic syndrome, congenital, 4b, fast-channel 9.8 C17orf107 CHRNE

Symptoms & Phenotypes for Myasthenic Syndrome, Congenital, 4a, Slow-Channel

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
ptosis
ophthalmoparesis

Muscle Soft Tissue:
easy fatigability
limb muscle weakness
bulbar muscle weakness
generalized hypotonia due to defect at the neuromuscular junction
decremental compound muscle action potential (cmap) response to repetitive nerve stimulation
more
Abdomen Gastrointestinal:
dysphagia
poor suck
poor feeding due to muscle weakness

Respiratory:
respiratory insufficiency due to muscle weakness (in some patients)


Clinical features from OMIM:

605809

Human phenotypes related to Myasthenic Syndrome, Congenital, 4a, Slow-Channel:

32 (show all 21)
# Description HPO Frequency HPO Source Accession
1 ptosis 32 HP:0000508
2 dysphagia 32 HP:0002015
3 feeding difficulties in infancy 32 HP:0008872
4 myopathy 32 HP:0003198
5 respiratory insufficiency due to muscle weakness 32 HP:0002747
6 strabismus 32 HP:0000486
7 respiratory distress 32 HP:0002098
8 ophthalmoparesis 32 HP:0000597
9 easy fatigability 32 HP:0003388
10 weak cry 32 HP:0001612
11 generalized hypotonia 32 HP:0001290
12 limb muscle weakness 32 HP:0003690
13 fatigable weakness 32 HP:0003473
14 poor suck 32 HP:0002033
15 bulbar palsy 32 HP:0001283
16 type 2 muscle fiber atrophy 32 HP:0003554
17 sudden episodic apnea 32 HP:0002882
18 apneic episodes precipitated by illness, fatigue, stress 32 HP:0002872
19 decreased miniature endplate potentials 32 HP:0003402
20 generalized hypotonia due to defect at the neuromuscular junction 32 HP:0003397
21 emg 32 HP:0003403

Drugs & Therapeutics for Myasthenic Syndrome, Congenital, 4a, Slow-Channel

Search Clinical Trials , NIH Clinical Center for Myasthenic Syndrome, Congenital, 4a, Slow-Channel

Genetic Tests for Myasthenic Syndrome, Congenital, 4a, Slow-Channel

Genetic tests related to Myasthenic Syndrome, Congenital, 4a, Slow-Channel:

# Genetic test Affiliating Genes
1 Myasthenic Syndrome, Congenital, 4a, Slow-Channel 29 CHRNE

Anatomical Context for Myasthenic Syndrome, Congenital, 4a, Slow-Channel

Publications for Myasthenic Syndrome, Congenital, 4a, Slow-Channel

Variations for Myasthenic Syndrome, Congenital, 4a, Slow-Channel

UniProtKB/Swiss-Prot genetic disease variations for Myasthenic Syndrome, Congenital, 4a, Slow-Channel:

75
# Symbol AA change Variation ID SNP ID
1 CHRNE p.Thr284Pro VAR_000292 rs121909510
2 CHRNE p.Leu289Phe VAR_000293 rs121909511
3 CHRNE p.Leu98Pro VAR_019567 rs28929768
4 CHRNE p.Leu241Phe VAR_019568 rs28999110
5 CHRNE p.Val285Ala VAR_077364

ClinVar genetic disease variations for Myasthenic Syndrome, Congenital, 4a, Slow-Channel:

6 (show top 50) (show all 164)
# Gene Variation Type Significance SNP ID Assembly Location
1 CHRNE NM_000080.3(CHRNE): c.850A> C (p.Thr284Pro) single nucleotide variant Pathogenic rs121909510 GRCh37 Chromosome 17, 4804155: 4804155
2 CHRNE NM_000080.3(CHRNE): c.850A> C (p.Thr284Pro) single nucleotide variant Pathogenic rs121909510 GRCh38 Chromosome 17, 4900860: 4900860
3 CHRNE NM_000080.3(CHRNE): c.865C> T (p.Leu289Phe) single nucleotide variant Pathogenic rs121909511 GRCh37 Chromosome 17, 4804140: 4804140
4 CHRNE NM_000080.3(CHRNE): c.865C> T (p.Leu289Phe) single nucleotide variant Pathogenic rs121909511 GRCh38 Chromosome 17, 4900845: 4900845
5 CHRNE NM_000080.3(CHRNE): c.422C> T (p.Pro141Leu) single nucleotide variant Likely pathogenic rs121909512 GRCh37 Chromosome 17, 4805305: 4805305
6 CHRNE NM_000080.3(CHRNE): c.422C> T (p.Pro141Leu) single nucleotide variant Likely pathogenic rs121909512 GRCh38 Chromosome 17, 4902010: 4902010
7 CHRNE NM_000080.3(CHRNE): c.250C> T (p.Arg84Ter) single nucleotide variant Pathogenic rs121909513 GRCh37 Chromosome 17, 4805606: 4805606
8 CHRNE NM_000080.3(CHRNE): c.250C> T (p.Arg84Ter) single nucleotide variant Pathogenic rs121909513 GRCh38 Chromosome 17, 4902311: 4902311
9 CHRNE NM_000080.3(CHRNE): c.971delT (p.Ile324Thrfs) deletion Pathogenic rs879255562 GRCh38 Chromosome 17, 4899529: 4899529
10 CHRNE NM_000080.3(CHRNE): c.971delT (p.Ile324Thrfs) deletion Pathogenic rs879255562 GRCh37 Chromosome 17, 4802824: 4802824
11 CHRNE NM_000080.3(CHRNE): c.721C> T (p.Leu241Phe) single nucleotide variant Pathogenic rs28999110 GRCh37 Chromosome 17, 4804366: 4804366
12 CHRNE NM_000080.3(CHRNE): c.721C> T (p.Leu241Phe) single nucleotide variant Pathogenic rs28999110 GRCh38 Chromosome 17, 4901071: 4901071
13 CHRNE NM_000080.3(CHRNE): c.614_620delGGGCCAT (p.Trp205Serfs) deletion Pathogenic rs753828284 GRCh38 Chromosome 17, 4901172: 4901178
14 CHRNE NM_000080.3(CHRNE): c.614_620delGGGCCAT (p.Trp205Serfs) deletion Pathogenic rs753828284 GRCh37 Chromosome 17, 4804467: 4804473
15 CHRNE NM_000080.3(CHRNE): c.37G> A (p.Gly13Arg) single nucleotide variant Uncertain significance rs372635387 GRCh37 Chromosome 17, 4806322: 4806322
16 CHRNE NM_000080.3(CHRNE): c.37G> A (p.Gly13Arg) single nucleotide variant Uncertain significance rs372635387 GRCh38 Chromosome 17, 4903027: 4903027
17 CHRNE NM_000080.3(CHRNE): c.488C> T (p.Ser163Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs121909516 GRCh37 Chromosome 17, 4805239: 4805239
18 CHRNE NM_000080.3(CHRNE): c.488C> T (p.Ser163Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs121909516 GRCh38 Chromosome 17, 4901944: 4901944
19 CHRNE NM_000080.3(CHRNE): c.892_894delTCT (p.Ser298del) deletion Pathogenic rs398122830 GRCh37 Chromosome 17, 4804111: 4804113
20 CHRNE NM_000080.3(CHRNE): c.892_894delTCT (p.Ser298del) deletion Pathogenic rs398122830 GRCh38 Chromosome 17, 4900816: 4900818
21 CHRNE NM_000080.3(CHRNE): c.710G> T (p.Arg237Leu) single nucleotide variant Pathogenic rs201434993 GRCh37 Chromosome 17, 4804377: 4804377
22 CHRNE NM_000080.3(CHRNE): c.710G> T (p.Arg237Leu) single nucleotide variant Pathogenic rs201434993 GRCh38 Chromosome 17, 4901082: 4901082
23 CHRNE NM_000080.3(CHRNE): c.1017C> G (p.Ser339=) single nucleotide variant Benign/Likely benign rs114454383 GRCh37 Chromosome 17, 4802778: 4802778
24 CHRNE NM_000080.3(CHRNE): c.1017C> G (p.Ser339=) single nucleotide variant Benign/Likely benign rs114454383 GRCh38 Chromosome 17, 4899483: 4899483
25 CHRNE NM_000080.3(CHRNE): c.1402G> C (p.Val468Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs139171143 GRCh37 Chromosome 17, 4802111: 4802111
26 CHRNE NM_000080.3(CHRNE): c.1402G> C (p.Val468Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs139171143 GRCh38 Chromosome 17, 4898816: 4898816
27 CHRNE NM_000080.3(CHRNE): c.45C> T (p.Leu15=) single nucleotide variant Benign/Likely benign rs34563587 GRCh37 Chromosome 17, 4806314: 4806314
28 CHRNE NM_000080.3(CHRNE): c.45C> T (p.Leu15=) single nucleotide variant Benign/Likely benign rs34563587 GRCh38 Chromosome 17, 4903019: 4903019
29 CHRNE NM_000080.3(CHRNE): c.519C> T (p.Ala173=) single nucleotide variant Benign/Likely benign rs33970119 GRCh37 Chromosome 17, 4804902: 4804902
30 CHRNE NM_000080.3(CHRNE): c.519C> T (p.Ala173=) single nucleotide variant Benign/Likely benign rs33970119 GRCh38 Chromosome 17, 4901607: 4901607
31 CHRNE NM_000080.3(CHRNE): c.53G> T (p.Gly18Val) single nucleotide variant Benign/Likely benign rs4790235 GRCh37 Chromosome 17, 4806052: 4806052
32 CHRNE NM_000080.3(CHRNE): c.53G> T (p.Gly18Val) single nucleotide variant Benign/Likely benign rs4790235 GRCh38 Chromosome 17, 4902757: 4902757
33 CHRNE NM_000080.3(CHRNE): c.1327delG (p.Glu443LysfsTer64) deletion Pathogenic rs763258280 GRCh37 Chromosome 17, 4802186: 4802186
34 CHRNE NM_000080.3(CHRNE): c.1327delG (p.Glu443LysfsTer64) deletion Pathogenic rs763258280 GRCh38 Chromosome 17, 4898891: 4898891
35 CHRNE NM_000080.3(CHRNE): c.130dupG (p.Glu44GlyfsTer3) duplication Pathogenic rs762368691 GRCh38 Chromosome 17, 4902680: 4902680
36 CHRNE NM_000080.3(CHRNE): c.130dupG (p.Glu44GlyfsTer3) duplication Pathogenic rs762368691 GRCh37 Chromosome 17, 4805975: 4805975
37 CHRNE NM_000080.3(CHRNE): c.1425C> T (p.Leu475=) single nucleotide variant Conflicting interpretations of pathogenicity rs151193377 GRCh37 Chromosome 17, 4802088: 4802088
38 CHRNE NM_000080.3(CHRNE): c.1425C> T (p.Leu475=) single nucleotide variant Conflicting interpretations of pathogenicity rs151193377 GRCh38 Chromosome 17, 4898793: 4898793
39 CHRNE NM_000080.3(CHRNE): c.1416C> T (p.Leu472=) single nucleotide variant Benign/Likely benign rs145456588 GRCh38 Chromosome 17, 4898802: 4898802
40 CHRNE NM_000080.3(CHRNE): c.1416C> T (p.Leu472=) single nucleotide variant Benign/Likely benign rs145456588 GRCh37 Chromosome 17, 4802097: 4802097
41 CHRNE NM_000080.3(CHRNE): c.966C> T (p.Cys322=) single nucleotide variant Benign/Likely benign rs56377005 GRCh38 Chromosome 17, 4899534: 4899534
42 CHRNE NM_000080.3(CHRNE): c.966C> T (p.Cys322=) single nucleotide variant Benign/Likely benign rs56377005 GRCh37 Chromosome 17, 4802829: 4802829
43 CHRNE NM_000080.3(CHRNE): c.103T> C (p.Tyr35His) single nucleotide variant Conflicting interpretations of pathogenicity rs144169073 GRCh37 Chromosome 17, 4806002: 4806002
44 CHRNE NM_000080.3(CHRNE): c.103T> C (p.Tyr35His) single nucleotide variant Conflicting interpretations of pathogenicity rs144169073 GRCh38 Chromosome 17, 4902707: 4902707
45 CHRNE NM_000080.3(CHRNE): c.1093delG (p.Ala365Profs) deletion Pathogenic rs886043239 GRCh37 Chromosome 17, 4802619: 4802619
46 CHRNE NM_000080.3(CHRNE): c.1093delG (p.Ala365Profs) deletion Pathogenic rs886043239 GRCh38 Chromosome 17, 4899324: 4899324
47 CHRNE NM_000080.3(CHRNE): c.1220-5G> A single nucleotide variant Conflicting interpretations of pathogenicity rs188564977 GRCh38 Chromosome 17, 4899112: 4899112
48 CHRNE NM_000080.3(CHRNE): c.1220-5G> A single nucleotide variant Conflicting interpretations of pathogenicity rs188564977 GRCh37 Chromosome 17, 4802407: 4802407
49 CHRNE NM_000080.3(CHRNE): c.1242C> A (p.Gly414=) single nucleotide variant Conflicting interpretations of pathogenicity rs370770111 GRCh38 Chromosome 17, 4899085: 4899085
50 CHRNE NM_000080.3(CHRNE): c.1242C> A (p.Gly414=) single nucleotide variant Conflicting interpretations of pathogenicity rs370770111 GRCh37 Chromosome 17, 4802380: 4802380

Expression for Myasthenic Syndrome, Congenital, 4a, Slow-Channel

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Pathways for Myasthenic Syndrome, Congenital, 4a, Slow-Channel

GO Terms for Myasthenic Syndrome, Congenital, 4a, Slow-Channel

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