MCID: MYS059
MIFTS: 25

Myasthenic Syndrome, Congenital, 4a, Slow-Channel

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 strabismus and ptosis

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 29.9 C17orf107 CHRNE
2 myasthenic syndrome, congenital, 4c, associated with acetylcholine receptor deficiency 11.4
3 myasthenic syndrome, congenital, 4b, fast-channel 9.2 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:
limb muscle weakness
easy fatigability
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 20)
# Description HPO Frequency HPO Source Accession
1 strabismus 32 HP:0000486
2 ptosis 32 HP:0000508
3 ophthalmoparesis 32 HP:0000597
4 bulbar palsy 32 HP:0001283
5 generalized hypotonia 32 HP:0001290
6 weak cry 32 HP:0001612
7 dysphagia 32 HP:0002015
8 poor suck 32 HP:0002033
9 respiratory distress 32 HP:0002098
10 respiratory insufficiency due to muscle weakness 32 HP:0002747
11 apneic episodes precipitated by illness, fatigue, stress 32 HP:0002872
12 sudden episodic apnea 32 HP:0002882
13 easy fatigability 32 HP:0003388
14 generalized hypotonia due to defect at the neuromuscular junction 32 HP:0003397
15 decreased miniature endplate potentials 32 HP:0003402
16 emg 32 HP:0003403
17 fatigable weakness 32 HP:0003473
18 type 2 muscle fiber atrophy 32 HP:0003554
19 limb muscle weakness 32 HP:0003690
20 feeding difficulties in infancy 32 HP:0008872

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 106)
# 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.971delT (p.Ile324Thrfs) deletion Pathogenic rs879255562 GRCh38 Chromosome 17, 4899529: 4899529
6 CHRNE NM_000080.3(CHRNE): c.971delT (p.Ile324Thrfs) deletion Pathogenic rs879255562 GRCh37 Chromosome 17, 4802824: 4802824
7 CHRNE NM_000080.3(CHRNE): c.721C> T (p.Leu241Phe) single nucleotide variant Pathogenic rs28999110 GRCh37 Chromosome 17, 4804366: 4804366
8 CHRNE NM_000080.3(CHRNE): c.721C> T (p.Leu241Phe) single nucleotide variant Pathogenic rs28999110 GRCh38 Chromosome 17, 4901071: 4901071
9 CHRNE NM_000080.3(CHRNE): c.614_620delGGGCCAT (p.Trp205Serfs) deletion Pathogenic rs753828284 GRCh38 Chromosome 17, 4901172: 4901178
10 CHRNE NM_000080.3(CHRNE): c.614_620delGGGCCAT (p.Trp205Serfs) deletion Pathogenic rs753828284 GRCh37 Chromosome 17, 4804467: 4804473
11 CHRNE NM_000080.3(CHRNE): c.892_894delTCT (p.Ser298del) deletion Pathogenic rs398122830 GRCh37 Chromosome 17, 4804111: 4804113
12 CHRNE NM_000080.3(CHRNE): c.892_894delTCT (p.Ser298del) deletion Pathogenic rs398122830 GRCh38 Chromosome 17, 4900816: 4900818
13 CHRNE NM_000080.3(CHRNE): c.710G> T (p.Arg237Leu) single nucleotide variant Pathogenic rs201434993 GRCh37 Chromosome 17, 4804377: 4804377
14 CHRNE NM_000080.3(CHRNE): c.710G> T (p.Arg237Leu) single nucleotide variant Pathogenic rs201434993 GRCh38 Chromosome 17, 4901082: 4901082
15 CHRNE NM_000080.3(CHRNE): c.1327delG (p.Glu443LysfsTer64) deletion Pathogenic rs763258280 GRCh37 Chromosome 17, 4802186: 4802186
16 CHRNE NM_000080.3(CHRNE): c.1327delG (p.Glu443LysfsTer64) deletion Pathogenic rs763258280 GRCh38 Chromosome 17, 4898891: 4898891
17 CHRNE NM_000080.3(CHRNE): c.130dupG (p.Glu44GlyfsTer3) duplication Pathogenic rs762368691 GRCh38 Chromosome 17, 4902680: 4902680
18 CHRNE NM_000080.3(CHRNE): c.130dupG (p.Glu44GlyfsTer3) duplication Pathogenic rs762368691 GRCh37 Chromosome 17, 4805975: 4805975
19 CHRNE NM_000080.3(CHRNE): c.1425C> T (p.Leu475=) single nucleotide variant Conflicting interpretations of pathogenicity rs151193377 GRCh37 Chromosome 17, 4802088: 4802088
20 CHRNE NM_000080.3(CHRNE): c.1425C> T (p.Leu475=) single nucleotide variant Conflicting interpretations of pathogenicity rs151193377 GRCh38 Chromosome 17, 4898793: 4898793
21 CHRNE NM_000080.3(CHRNE): c.1416C> T (p.Leu472=) single nucleotide variant Benign rs145456588 GRCh38 Chromosome 17, 4898802: 4898802
22 CHRNE NM_000080.3(CHRNE): c.1416C> T (p.Leu472=) single nucleotide variant Benign rs145456588 GRCh37 Chromosome 17, 4802097: 4802097
23 CHRNE NM_000080.3(CHRNE): c.966C> T (p.Cys322=) single nucleotide variant Benign/Likely benign rs56377005 GRCh38 Chromosome 17, 4899534: 4899534
24 CHRNE NM_000080.3(CHRNE): c.966C> T (p.Cys322=) single nucleotide variant Benign/Likely benign rs56377005 GRCh37 Chromosome 17, 4802829: 4802829
25 CHRNE NM_000080.3(CHRNE): c.103T> C (p.Tyr35His) single nucleotide variant Conflicting interpretations of pathogenicity rs144169073 GRCh37 Chromosome 17, 4806002: 4806002
26 CHRNE NM_000080.3(CHRNE): c.103T> C (p.Tyr35His) single nucleotide variant Conflicting interpretations of pathogenicity rs144169073 GRCh38 Chromosome 17, 4902707: 4902707
27 CHRNE NM_000080.3(CHRNE): c.1093delG (p.Ala365Profs) deletion Pathogenic rs886043239 GRCh37 Chromosome 17, 4802619: 4802619
28 CHRNE NM_000080.3(CHRNE): c.1093delG (p.Ala365Profs) deletion Pathogenic rs886043239 GRCh38 Chromosome 17, 4899324: 4899324
29 CHRNE NM_000080.3(CHRNE): c.1220-5G> A single nucleotide variant Conflicting interpretations of pathogenicity rs188564977 GRCh38 Chromosome 17, 4899112: 4899112
30 CHRNE NM_000080.3(CHRNE): c.1220-5G> A single nucleotide variant Conflicting interpretations of pathogenicity rs188564977 GRCh37 Chromosome 17, 4802407: 4802407
31 CHRNE NM_000080.3(CHRNE): c.1242C> A (p.Gly414=) single nucleotide variant Conflicting interpretations of pathogenicity rs370770111 GRCh38 Chromosome 17, 4899085: 4899085
32 CHRNE NM_000080.3(CHRNE): c.1242C> A (p.Gly414=) single nucleotide variant Conflicting interpretations of pathogenicity rs370770111 GRCh37 Chromosome 17, 4802380: 4802380
33 CHRNE NM_000080.3(CHRNE): c.723C> T (p.Leu241=) single nucleotide variant Conflicting interpretations of pathogenicity rs886053126 GRCh38 Chromosome 17, 4901069: 4901069
34 CHRNE NM_000080.3(CHRNE): c.723C> T (p.Leu241=) single nucleotide variant Conflicting interpretations of pathogenicity rs886053126 GRCh37 Chromosome 17, 4804364: 4804364
35 CHRNE NM_000080.3(CHRNE): c.1033-6_1033-1dupCCCCAG duplication Uncertain significance rs886053123 GRCh38 Chromosome 17, 4899385: 4899390
36 CHRNE NM_000080.3(CHRNE): c.1033-6_1033-1dupCCCCAG duplication Uncertain significance rs886053123 GRCh37 Chromosome 17, 4802680: 4802685
37 CHRNE NM_000080.3(CHRNE): c.901G> A (p.Val301Met) single nucleotide variant Conflicting interpretations of pathogenicity rs140023380 GRCh37 Chromosome 17, 4804104: 4804104
38 CHRNE NM_000080.3(CHRNE): c.901G> A (p.Val301Met) single nucleotide variant Conflicting interpretations of pathogenicity rs140023380 GRCh38 Chromosome 17, 4900809: 4900809
39 CHRNE NM_000080.3(CHRNE): c.820A> G (p.Thr274Ala) single nucleotide variant Uncertain significance rs774407731 GRCh38 Chromosome 17, 4900890: 4900890
40 CHRNE NM_000080.3(CHRNE): c.820A> G (p.Thr274Ala) single nucleotide variant Uncertain significance rs774407731 GRCh37 Chromosome 17, 4804185: 4804185
41 CHRNE NM_000080.3(CHRNE): c.433C> T (p.Arg145Cys) single nucleotide variant Uncertain significance rs1064795871 GRCh38 Chromosome 17, 4901999: 4901999
42 CHRNE NM_000080.3(CHRNE): c.433C> T (p.Arg145Cys) single nucleotide variant Uncertain significance rs1064795871 GRCh37 Chromosome 17, 4805294: 4805294
43 CHRNE NM_000080.3(CHRNE): c.384_389delGCTCGT (p.Leu129_Val130del) deletion Uncertain significance GRCh38 Chromosome 17, 4902043: 4902048
44 CHRNE NM_000080.3(CHRNE): c.384_389delGCTCGT (p.Leu129_Val130del) deletion Uncertain significance GRCh37 Chromosome 17, 4805338: 4805343
45 CHRNE NM_000080.3(CHRNE): c.918-6C> G single nucleotide variant Benign rs141408756 GRCh37 Chromosome 17, 4802883: 4802883
46 CHRNE NM_000080.3(CHRNE): c.918-6C> G single nucleotide variant Benign rs141408756 GRCh38 Chromosome 17, 4899588: 4899588
47 CHRNE NM_000080.3(CHRNE): c.572A> T (p.Lys191Met) single nucleotide variant Uncertain significance GRCh37 Chromosome 17, 4804849: 4804849
48 CHRNE NM_000080.3(CHRNE): c.572A> T (p.Lys191Met) single nucleotide variant Uncertain significance GRCh38 Chromosome 17, 4901554: 4901554
49 CHRNE NM_000080.3(CHRNE): c.250delC (p.Arg84Aspfs) deletion Pathogenic GRCh38 Chromosome 17, 4902311: 4902311
50 CHRNE NM_000080.3(CHRNE): c.250delC (p.Arg84Aspfs) deletion Pathogenic GRCh37 Chromosome 17, 4805606: 4805606

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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