MCID: MYS046
MIFTS: 26

Myasthenic Syndrome, Congenital, 1a, Slow-Channel

Categories: Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Myasthenic Syndrome, Congenital, 1a, Slow-Channel

MalaCards integrated aliases for Myasthenic Syndrome, Congenital, 1a, Slow-Channel:

Name: Myasthenic Syndrome, Congenital, 1a, Slow-Channel 57 75
Cms1a 57 12 75
Congenital Myasthenic Syndrome Type Iia 12 75
Cms Iia 12 75
Cms2a 12 75
Myasthenic Syndrome, Congenital, Type Iia, Formerly; Cms2a, Formerly 57
Myasthenic Syndrome, Congenital, Postsynaptic Slow-Channel 73
Congenital Myasthenic Syndrome Post-Synaptic Slow-Channel 75
Myasthenic Syndrome, Congenital, Type 1a, Slow-Channel 40
Myasthenic Syndrome, Congenital, Type 2a, Slow-Channel 40
Myasthenic Syndrome, Congenital, Type Iia, Formerly 57
Congenital Myasthenic Syndrome 1a, Slow-Channel 12
Congenital Myasthenic Syndrome 2a Slow-Channel 12
Myasthenic Syndromes, Congenital, Slow Channel 73
Myasthenic Syndrome, Congenital, Slow-Channel 75
Congenital Myasthenic Syndrome 1a 12
Congenital Myasthenic Syndrome 2a 12
Cms Iia, Formerly 57
Cms2a, Formerly 57
Sccms 75

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
variable age at onset
usually symptomatic in adulthood with history of weakness since infancy or childhood
exacerbation of symptoms during or after pregnancy
progressive disorder due to secondary myopathy
poor response to acetylcholinesterase inhibitors
quinidine therapy may be effective
fluoxetine therapy may be effective


HPO:

32
myasthenic syndrome, congenital, 1a, slow-channel:
Inheritance autosomal recessive inheritance autosomal dominant inheritance
Onset and clinical course onset


Classifications:



Summaries for Myasthenic Syndrome, Congenital, 1a, Slow-Channel

OMIM : 57 Congenital myasthenic syndromes (CMS) are a group of inherited disorders affecting the neuromuscular junction (NMJ). Patients present clinically with onset of variable muscle weakness between infancy and adulthood. These disorders have been classified according to the location of the defect: presynaptic, synaptic, and postsynaptic, as well as by pathologic mechanism and electrophysiologic studies (i.e., acetylcholine receptor (AChR) deficiency, slow-channel or fast-channel kinetic defects at the AChR) (summary by Engel et al., 2003; Engel et al., 2015). Approximately 10% of CMS cases are presynaptic, 15% are synaptic, and 75% are postsynaptic, the majority of which are caused by AChR deficiency (Engel et al., 2003). Slow-channel congenital myasthenic syndrome (SCCMS) is a disorder of the postsynaptic NMJ characterized by early-onset progressive muscle weakness. The disorder results from kinetic abnormalities of the AChR channel, specifically 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). (601462)

MalaCards based summary : Myasthenic Syndrome, Congenital, 1a, Slow-Channel, also known as cms1a, is related to myasthenic syndrome, congenital, 6, presynaptic and slow-channel congenital myasthenic syndrome. An important gene associated with Myasthenic Syndrome, Congenital, 1a, Slow-Channel is CHRNA1 (Cholinergic Receptor Nicotinic Alpha 1 Subunit). Related phenotypes are high palate and ptosis

Disease Ontology : 12 A congenital myasthenic syndrome characterized by predominantly autosomal dominant inheritance of defects in postsynaptic neuromuscular junctions and early-onset progressive muscle weakness that has material basis in mutation in the CHRNA1 gene on chromosome 2q.

UniProtKB/Swiss-Prot : 75 Myasthenic syndrome, congenital, 1A, slow-channel: A common congenital myasthenic syndrome. Congenital myasthenic syndromes are characterized by 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. CMS1A 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.

Related Diseases for Myasthenic Syndrome, Congenital, 1a, 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, 1a, Slow-Channel via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 27)
# Related Disease Score Top Affiliating Genes
1 myasthenic syndrome, congenital, 6, presynaptic 11.4
2 slow-channel congenital myasthenic syndrome 11.1
3 congenital myasthenic syndrome with episodic apnea 10.9
4 myasthenic syndrome, congenital, 10 10.7
5 myasthenic syndrome, congenital, 5 10.7
6 myasthenic syndrome, congenital, 4a, slow-channel 10.7
7 myasthenic syndrome, congenital, 1b, fast-channel 10.7
8 myasthenic syndrome, congenital, 4c, associated with acetylcholine receptor deficiency 10.7
9 myasthenic syndrome, congenital, 12 10.7
10 myasthenic syndrome, congenital, 16 10.7
11 myasthenic syndrome, congenital, 13 10.7
12 myasthenic syndrome, congenital, 8 10.7
13 muscular dystrophy-dystroglycanopathy , type c, 14 10.7
14 myasthenic syndrome, congenital, 7, presynaptic 10.7
15 myasthenic syndrome, congenital, 15 10.7
16 myasthenic syndrome, congenital, 14 10.7
17 myasthenic syndrome, congenital, 2a, slow-channel 10.7
18 myasthenic syndrome, congenital, 2c, associated with acetylcholine receptor deficiency 10.7
19 myasthenic syndrome, congenital, 3a, slow-channel 10.7
20 myasthenic syndrome, congenital, 3b, fast-channel 10.7
21 myasthenic syndrome, congenital, 3c, associated with acetylcholine receptor deficiency 10.7
22 myasthenic syndrome, congenital, 4b, fast-channel 10.7
23 myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency 10.7
24 myasthenic syndrome, congenital, 11, associated with acetylcholine receptor deficiency 10.7
25 myasthenic syndrome, congenital, 18 10.7
26 myasthenic syndrome, congenital, 19 10.7
27 myasthenic syndrome, congenital, 20, presynaptic 10.7

Graphical network of the top 20 diseases related to Myasthenic Syndrome, Congenital, 1a, Slow-Channel:



Diseases related to Myasthenic Syndrome, Congenital, 1a, Slow-Channel

Symptoms & Phenotypes for Myasthenic Syndrome, Congenital, 1a, Slow-Channel

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
ptosis
ophthalmoplegia

Abdomen Gastrointestinal:
dysphagia
feeding difficulties

Respiratory:
respiratory insufficiency, episodic

Muscle Soft Tissue:
dysarthria
scapular muscle weakness
generalized muscle weakness due to defect at the neuromuscular junction
cervical muscle weakness
extensor finger muscle weakness
more
Head And Neck Mouth:
high-arched palate (in some patients)


Clinical features from OMIM:

601462

Human phenotypes related to Myasthenic Syndrome, Congenital, 1a, Slow-Channel:

32 (show all 13)
# Description HPO Frequency HPO Source Accession
1 high palate 32 occasional (7.5%) HP:0000218
2 ptosis 32 HP:0000508
3 ophthalmoparesis 32 HP:0000597
4 ophthalmoplegia 32 HP:0000602
5 dysarthria 32 HP:0001260
6 dysphagia 32 HP:0002015
7 generalized muscle weakness 32 HP:0003324
8 prolonged miniature endplate currents 32 HP:0003436
9 decreased size of nerve terminals 32 HP:0003443
10 fatigable weakness 32 HP:0003473
11 type 2 muscle fiber atrophy 32 HP:0003554
12 intermittent episodes of respiratory insufficiency due to muscle weakness 32 HP:0004889
13 feeding difficulties 32 HP:0011968

Drugs & Therapeutics for Myasthenic Syndrome, Congenital, 1a, Slow-Channel

Search Clinical Trials , NIH Clinical Center for Myasthenic Syndrome, Congenital, 1a, Slow-Channel

Genetic Tests for Myasthenic Syndrome, Congenital, 1a, Slow-Channel

Anatomical Context for Myasthenic Syndrome, Congenital, 1a, Slow-Channel

Publications for Myasthenic Syndrome, Congenital, 1a, Slow-Channel

Variations for Myasthenic Syndrome, Congenital, 1a, Slow-Channel

UniProtKB/Swiss-Prot genetic disease variations for Myasthenic Syndrome, Congenital, 1a, Slow-Channel:

75
# Symbol AA change Variation ID SNP ID
1 CHRNA1 p.Gly198Ser VAR_000282 rs137852801
2 CHRNA1 p.Val201Met VAR_000283 rs137852799
3 CHRNA1 p.Asn262Lys VAR_000284 rs137852798
4 CHRNA1 p.Thr299Ile VAR_000285 rs137852800
5 CHRNA1 p.Ser314Ile VAR_000286 rs137852802
6 CHRNA1 p.Val294Phe VAR_021207 rs137852803
7 CHRNA1 p.Cys463Trp VAR_038601 rs137852808

ClinVar genetic disease variations for Myasthenic Syndrome, Congenital, 1a, Slow-Channel:

6
(show all 22)
# Gene Variation Type Significance SNP ID Assembly Location
1 CHRNA1 NM_001039523.2(CHRNA1): c.786C> G (p.Asn262Lys) single nucleotide variant Pathogenic rs137852798 GRCh37 Chromosome 2, 175618298: 175618298
2 CHRNA1 NM_001039523.2(CHRNA1): c.786C> G (p.Asn262Lys) single nucleotide variant Pathogenic rs137852798 GRCh38 Chromosome 2, 174753570: 174753570
3 CHRNA1 NM_001039523.2(CHRNA1): c.601G> A (p.Val201Met) single nucleotide variant Pathogenic rs137852799 GRCh37 Chromosome 2, 175618961: 175618961
4 CHRNA1 NM_001039523.2(CHRNA1): c.601G> A (p.Val201Met) single nucleotide variant Pathogenic rs137852799 GRCh38 Chromosome 2, 174754233: 174754233
5 CHRNA1 NM_001039523.2(CHRNA1): c.896C> T (p.Thr299Ile) single nucleotide variant Pathogenic rs137852800 GRCh37 Chromosome 2, 175614855: 175614855
6 CHRNA1 NM_001039523.2(CHRNA1): c.896C> T (p.Thr299Ile) single nucleotide variant Pathogenic rs137852800 GRCh38 Chromosome 2, 174750127: 174750127
7 CHRNA1 NM_000079.3(CHRNA1): c.517G> A (p.Gly173Ser) single nucleotide variant Pathogenic rs137852801 GRCh37 Chromosome 2, 175618970: 175618970
8 CHRNA1 NM_000079.3(CHRNA1): c.517G> A (p.Gly173Ser) single nucleotide variant Pathogenic rs137852801 GRCh38 Chromosome 2, 174754242: 174754242
9 CHRNA1 NM_001039523.2(CHRNA1): c.941G> T (p.Ser314Ile) single nucleotide variant Pathogenic rs137852802 GRCh37 Chromosome 2, 175614810: 175614810
10 CHRNA1 NM_001039523.2(CHRNA1): c.941G> T (p.Ser314Ile) single nucleotide variant Pathogenic rs137852802 GRCh38 Chromosome 2, 174750082: 174750082
11 CHRNA1 NM_000079.3(CHRNA1): c.805G> T (p.Val269Phe) single nucleotide variant Likely pathogenic rs137852803 GRCh37 Chromosome 2, 175614871: 175614871
12 CHRNA1 NM_000079.3(CHRNA1): c.805G> T (p.Val269Phe) single nucleotide variant Likely pathogenic rs137852803 GRCh38 Chromosome 2, 174750143: 174750143
13 CHRNA1 NM_001039523.2(CHRNA1): c.1389C> G (p.Cys463Trp) single nucleotide variant Pathogenic rs137852808 GRCh37 Chromosome 2, 175612912: 175612912
14 CHRNA1 NM_001039523.2(CHRNA1): c.1389C> G (p.Cys463Trp) single nucleotide variant Pathogenic rs137852808 GRCh38 Chromosome 2, 174748184: 174748184
15 CHRNA1 NM_000079.3(CHRNA1): c.737C> A (p.Ser246Tyr) single nucleotide variant Pathogenic rs483353046 GRCh37 Chromosome 2, 175618272: 175618272
16 CHRNA1 NM_000079.3(CHRNA1): c.737C> A (p.Ser246Tyr) single nucleotide variant Pathogenic rs483353046 GRCh38 Chromosome 2, 174753544: 174753544
17 CHRNA1 NM_000079.3(CHRNA1): c.737C> T (p.Ser246Phe) single nucleotide variant Pathogenic rs483353046 GRCh37 Chromosome 2, 175618272: 175618272
18 CHRNA1 NM_000079.3(CHRNA1): c.737C> T (p.Ser246Phe) single nucleotide variant Pathogenic rs483353046 GRCh38 Chromosome 2, 174753544: 174753544
19 CHRNA1 NM_000079.3(CHRNA1): c.1139T> C (p.Met380Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs149292107 GRCh37 Chromosome 2, 175613411: 175613411
20 CHRNA1 NM_000079.3(CHRNA1): c.1139T> C (p.Met380Thr) single nucleotide variant Conflicting interpretations of pathogenicity rs149292107 GRCh38 Chromosome 2, 174748683: 174748683
21 CHRNA1 NM_000079.3(CHRNA1): c.424G> A (p.Ala142Thr) single nucleotide variant Uncertain significance GRCh37 Chromosome 2, 175619063: 175619063
22 CHRNA1 NM_000079.3(CHRNA1): c.424G> A (p.Ala142Thr) single nucleotide variant Uncertain significance GRCh38 Chromosome 2, 174754335: 174754335

Expression for Myasthenic Syndrome, Congenital, 1a, Slow-Channel

Search GEO for disease gene expression data for Myasthenic Syndrome, Congenital, 1a, Slow-Channel.

Pathways for Myasthenic Syndrome, Congenital, 1a, Slow-Channel

GO Terms for Myasthenic Syndrome, Congenital, 1a, Slow-Channel

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