MCID: MYS055
MIFTS: 36

Myasthenic Syndrome, Congenital, 6, Presynaptic

Categories: Genetic diseases, Rare diseases, Eye diseases, Neuronal diseases

Aliases & Classifications for Myasthenic Syndrome, Congenital, 6, Presynaptic

MalaCards integrated aliases for Myasthenic Syndrome, Congenital, 6, Presynaptic:

Name: Myasthenic Syndrome, Congenital, 6, Presynaptic 53 71
Familial Infantile Myasthenia 12 28 69
Cmsea 53 12 71
Cms6 53 12 71
Myasthenic Syndrome, Congenital, Associated with Episodic Apnea 71 13
Familial Infantile Myasthenia Gravis 2 12 71
Congenital Myasthenic Syndrome 6 12 14
Fimg2 12 71
Myasthenic Syndrome, Presynaptic, Congenital, Associated with Episodic Apnea; Cmsea 53
Myasthenic Syndrome, Presynaptic, Congenital, Associated with Episodic Apnea 53
Congenital Myasthenic Syndrome Pre-Synaptic Associated with Episodic Apnea 71
Congenital Presynaptic Myasthenic Syndrome Associated with Episodic Apnea 12
Congenital Myasthenic Syndrome Type Ia2, Formerly; Cms1a2, Formerly 53
Myasthenia Gravis, Familial Infantile, 2, Formerly; Fimg2, Formerly 53
Myasthenia, Familial Infantile, Formerly; Fim, Formerly 53
Myasthenia Gravis, Familial Infantile, 2, Formerly 53
Congenital Myasthenic Syndrome Type Ia2, Formerly 53
Congenital Myasthenic Syndrome 6, Presynaptic 12
Myasthenia, Familial Infantile, Formerly 53
Congenital Myasthenic Syndrome Type Ia2 12
Congenital Myasthenic Syndrome Type 1a 71
Congenital Myasthenic Syndrome Type Ia 71
Cms Ia2, Formerly 53
Cms1a2, Formerly 53
Fimg2, Formerly 53
Fim, Formerly 53
Cms Ia2 12
Cms1a2 12
Cms-Ea 71
Cms Ia 71
Cms1a 71
Fim 12

Characteristics:

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
onset at birth or early childhood
favorable response to acetylcholinesterase inhibitors
symptoms often improve gradually with age
genetic heterogeneity (see cms1a1, )


HPO:

31
myasthenic syndrome, congenital, 6, presynaptic:
Onset and clinical course congenital onset
Inheritance heterogeneous autosomal recessive inheritance


Classifications:



Summaries for Myasthenic Syndrome, Congenital, 6, Presynaptic

UniProtKB/Swiss-Prot : 71 Myasthenic syndrome, congenital, 6, presynaptic: 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. CMS6 affected individuals have myasthenic symptoms since birth or early infancy, negative tests for anti-AChR antibodies, and abrupt episodic crises with increased weakness, bulbar paralysis, and apnea precipitated by undue exertion, fever, or excitement. CMS6 inheritance is autosomal recessive.

MalaCards based summary : Myasthenic Syndrome, Congenital, 6, Presynaptic, also known as familial infantile myasthenia, is related to congenital myasthenic syndrome and myasthenic syndrome, congenital, 1a, slow-channel, and has symptoms including respiratory distress, ophthalmoparesis and ptosis. An important gene associated with Myasthenic Syndrome, Congenital, 6, Presynaptic is CHAT (Choline O-Acetyltransferase). Affiliated tissues include testes.

OMIM : 53 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. CMS6 is an autosomal recessive CMS resulting from a presynaptic defect; patients have onset of symptoms in infancy or early childhood and tend to have sudden apneic episodes. Treatment with acetylcholinesterase inhibitors may be beneficial (summary by Engel et al., 2015). For a discussion of genetic heterogeneity of CMS, see CMS1A (601462). (254210)

Disease Ontology : 12 A congenital myasthenic syndrome characterized by autosomal recessive inheritance of a presynaptic defect resulting in onset of muscle weakeness in infancy or early childhood and a tendency to have sudden apneic episodes that has material basis in homozygous or compound heterozygous mutation in the CHAT gene on chromosome 10q.

Related Diseases for Myasthenic Syndrome, Congenital, 6, Presynaptic

Graphical network of the top 20 diseases related to Myasthenic Syndrome, Congenital, 6, Presynaptic:



Diseases related to Myasthenic Syndrome, Congenital, 6, Presynaptic

Symptoms & Phenotypes for Myasthenic Syndrome, Congenital, 6, Presynaptic

Symptoms via clinical synopsis from OMIM:

53
Respiratory:
respiratory distress
respiratory insufficiency due to muscle weakness
sudden episodic apnea, severe, may cause death
apneic episodes precipitated by illness, fatigue, stress

Abdomen Gastroin testinal:
dysphagia
poor suck
poor feeding due to muscle weakness

Muscle Soft Tissue:
muscle biopsy shows type 2 fiber atrophy

Skeletal:
arthrogryposis multiplex in severe cases

Head And Neck Eyes:
ophthalmoparesis
ptosis
strabismus

Voice:
weak cry

Neurologic Peripheral Nervous System:
bulbar muscle weakness
generalized hypotonia due to defect at the neuromuscular junction
mild-moderate fatigable weakness of limb muscles
emg shows decremental response of compound muscle action potential (cmap) to repetitive nerve stimulation
decreased miniature endplate potentials (mepp)
more
Immunology:
absence of acetylcholine receptor (achr) autoantibodies


Clinical features from OMIM:

254210

Human phenotypes related to Myasthenic Syndrome, Congenital, 6, Presynaptic:

31 (show all 18)
# Description HPO Frequency HPO Source Accession
1 respiratory distress 31 HP:0002098
2 ophthalmoparesis 31 HP:0000597
3 ptosis 31 HP:0000508
4 dysphagia 31 HP:0002015
5 respiratory insufficiency due to muscle weakness 31 HP:0002747
6 strabismus 31 HP:0000486
7 arthrogryposis multiplex congenita 31 HP:0002804
8 abnormality of the immune system 31 HP:0002715
9 weak cry 31 HP:0001612
10 fatigable weakness 31 HP:0003473
11 poor suck 31 HP:0002033
12 bulbar palsy 31 HP:0001283
13 type 2 muscle fiber atrophy 31 HP:0003554
14 sudden episodic apnea 31 HP:0002882
15 apneic episodes precipitated by illness, fatigue, stress 31 HP:0002872
16 generalized hypotonia due to defect at the neuromuscular junction 31 HP:0003397
17 emg 31 HP:0003403
18 decreased miniature endplate potentials 31 HP:0003402

UMLS symptoms related to Myasthenic Syndrome, Congenital, 6, Presynaptic:


ophthalmoparesis, respiratory distress, apnea

Drugs & Therapeutics for Myasthenic Syndrome, Congenital, 6, Presynaptic

Search Clinical Trials , NIH Clinical Center for Myasthenic Syndrome, Congenital, 6, Presynaptic

Genetic Tests for Myasthenic Syndrome, Congenital, 6, Presynaptic

Genetic tests related to Myasthenic Syndrome, Congenital, 6, Presynaptic:

# Genetic test Affiliating Genes
1 Familial Infantile Myasthenia 28 CHAT

Anatomical Context for Myasthenic Syndrome, Congenital, 6, Presynaptic

MalaCards organs/tissues related to Myasthenic Syndrome, Congenital, 6, Presynaptic:

38
Testes

Publications for Myasthenic Syndrome, Congenital, 6, Presynaptic

Articles related to Myasthenic Syndrome, Congenital, 6, Presynaptic:

# Title Authors Year
1
Mapping of the familial infantile myasthenia (congenital myasthenic syndrome type Ia) gene to chromosome 17p with evidence of genetic homogeneity. ( 9097970 )
1997

Variations for Myasthenic Syndrome, Congenital, 6, Presynaptic

UniProtKB/Swiss-Prot genetic disease variations for Myasthenic Syndrome, Congenital, 6, Presynaptic:

71
# Symbol AA change Variation ID SNP ID
1 CHAT p.Leu210Pro VAR_011666 rs28930071
2 CHAT p.Pro211Ala VAR_011667 rs121912815
3 CHAT p.Ile305Thr VAR_011668 rs28929482
4 CHAT p.Arg420Cys VAR_011669 rs121912822
5 CHAT p.Glu441Lys VAR_011670 rs28930070
6 CHAT p.Arg482Gly VAR_011671 rs28929481
7 CHAT p.Ser498Leu VAR_011672 rs121912821
8 CHAT p.Val506Leu VAR_011673 rs121912817
9 CHAT p.Arg560His VAR_011674 rs121912819
10 CHAT p.Ile336Thr VAR_038605 rs121912823

ClinVar genetic disease variations for Myasthenic Syndrome, Congenital, 6, Presynaptic:

6 (show all 17)
# Gene Variation Type Significance SNP ID Assembly Location
1 CHAT CHAT, 2-BP INS, 523CC insertion Pathogenic
2 CHAT NM_020549.4(CHAT): c.631C> G (p.Pro211Ala) single nucleotide variant Pathogenic rs121912815 GRCh37 Chromosome 10, 50828592: 50828592
3 CHAT NM_020549.4(CHAT): c.1321G> A (p.Glu441Lys) single nucleotide variant Pathogenic rs121912816 GRCh37 Chromosome 10, 50856592: 50856592
4 CHAT NM_020549.4(CHAT): c.1516G> T (p.Val506Leu) single nucleotide variant Pathogenic rs121912817 GRCh37 Chromosome 10, 50859934: 50859934
5 CHAT NM_020549.4(CHAT): c.1444A> G (p.Arg482Gly) single nucleotide variant Pathogenic rs121912818 GRCh37 Chromosome 10, 50857615: 50857615
6 CHAT NM_020549.4(CHAT): c.1679G> A (p.Arg560His) single nucleotide variant Pathogenic rs121912819 GRCh37 Chromosome 10, 50863185: 50863185
7 CHAT NM_020549.4(CHAT): c.629T> C (p.Leu210Pro) single nucleotide variant Pathogenic rs121912820 GRCh37 Chromosome 10, 50828590: 50828590
8 CHAT NM_020549.4(CHAT): c.1493C> T (p.Ser498Leu) single nucleotide variant Pathogenic rs121912821 GRCh37 Chromosome 10, 50857664: 50857664
9 CHAT NM_020549.4(CHAT): c.914T> C (p.Ile305Thr) single nucleotide variant Pathogenic rs75466054 GRCh37 Chromosome 10, 50833680: 50833680
10 CHAT NM_020549.4(CHAT): c.1258C> T (p.Arg420Cys) single nucleotide variant Pathogenic rs121912822 GRCh37 Chromosome 10, 50854697: 50854697
11 CHAT NM_020549.4(CHAT): c.1007T> C (p.Ile336Thr) single nucleotide variant Pathogenic rs121912823 GRCh37 Chromosome 10, 50835727: 50835727
12 CHAT NM_020549.4(CHAT): c.418C> T (p.Gln140Ter) single nucleotide variant Pathogenic rs794727516 GRCh37 Chromosome 10, 50827801: 50827801
13 CHAT NM_020549.4(CHAT): c.85A> T (p.Arg29Ter) single nucleotide variant Pathogenic rs772025588 GRCh37 Chromosome 10, 50822320: 50822320
14 CHAT NM_020549.4(CHAT): c.620G> A (p.Arg207His) single nucleotide variant Pathogenic/Likely pathogenic rs764497513 GRCh37 Chromosome 10, 50828581: 50828581
15 CHAT NM_020549.4(CHAT): c.635T> A (p.Val212Asp) single nucleotide variant Likely pathogenic GRCh38 Chromosome 10, 49620550: 49620550
16 CHAT NM_020549.4(CHAT): c.1642C> T (p.Arg548Ter) single nucleotide variant Pathogenic rs369251527 GRCh37 Chromosome 10, 50863148: 50863148
17 CHAT NM_020549.4(CHAT): c.669delG (p.Gln223Hisfs) deletion Pathogenic GRCh37 Chromosome 10, 50828630: 50828630

Expression for Myasthenic Syndrome, Congenital, 6, Presynaptic

Search GEO for disease gene expression data for Myasthenic Syndrome, Congenital, 6, Presynaptic.

Pathways for Myasthenic Syndrome, Congenital, 6, Presynaptic

GO Terms for Myasthenic Syndrome, Congenital, 6, Presynaptic

Biological processes related to Myasthenic Syndrome, Congenital, 6, Presynaptic according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytoskeleton organization GO:0007010 9.33 ZMYM2 ZMYM3 ZMYM6
2 phosphatidylinositol-mediated signaling GO:0048015 9.32 CSF1R FGFR1
3 photoreceptor cell maintenance GO:0045494 9.26 BBS2 TULP1
4 peptidyl-tyrosine phosphorylation GO:0018108 9.13 CSF1R FGFR1 ZMYM2
5 regulation of cell morphogenesis GO:0022604 8.8 ZMYM2 ZMYM3 ZMYM6

Molecular functions related to Myasthenic Syndrome, Congenital, 6, Presynaptic according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transmembrane receptor protein tyrosine kinase activity GO:0004714 9.16 CSF1R FGFR1
2 RNA polymerase II transcription factor activity, sequence-specific DNA binding GO:0000981 9.13 ZMYM2 ZMYM3 ZMYM6
3 protein tyrosine kinase activity GO:0004713 8.8 CSF1R FGFR1 ZMYM2

Sources for Myasthenic Syndrome, Congenital, 6, Presynaptic

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10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
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29 HGMD
30 HMDB
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58 PubMed
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65 SNOMED-CT via HPO
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70 UMLS via Orphanet
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