MCID: MYS055
MIFTS: 35

Myasthenic Syndrome, Congenital, 6, Presynaptic

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

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

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

Name: Myasthenic Syndrome, Congenital, 6, Presynaptic 57 75
Familial Infantile Myasthenia 12 29 6 73
Cmsea 57 12 75
Cms6 57 12 75
Myasthenic Syndrome, Congenital, Associated with Episodic Apnea 75 13
Familial Infantile Myasthenia Gravis 2 12 75
Congenital Myasthenic Syndrome 6 12 15
Fimg2 12 75
Myasthenic Syndrome, Presynaptic, Congenital, Associated with Episodic Apnea; Cmsea 57
Myasthenic Syndrome, Presynaptic, Congenital, Associated with Episodic Apnea 57
Congenital Myasthenic Syndrome Pre-Synaptic Associated with Episodic Apnea 75
Congenital Presynaptic Myasthenic Syndrome Associated with Episodic Apnea 12
Congenital Myasthenic Syndrome Type Ia2, Formerly; Cms1a2, Formerly 57
Myasthenia Gravis, Familial Infantile, 2, Formerly; Fimg2, Formerly 57
Myasthenia, Familial Infantile, Formerly; Fim, Formerly 57
Myasthenic Syndrome, Congenital, Type 6, Presynaptic 40
Myasthenia Gravis, Familial Infantile, 2, Formerly 57
Congenital Myasthenic Syndrome Type Ia2, Formerly 57
Congenital Myasthenic Syndrome 6, Presynaptic 12
Myasthenia, Familial Infantile, Formerly 57
Congenital Myasthenic Syndrome Type Ia2 12
Congenital Myasthenic Syndrome Type 1a 75
Congenital Myasthenic Syndrome Type Ia 75
Cms Ia2, Formerly 57
Cms1a2, Formerly 57
Fimg2, Formerly 57
Fim, Formerly 57
Cms Ia2 12
Cms1a2 12
Cms-Ea 75
Cms Ia 75
Cms1a 75
Fim 12

Characteristics:

OMIM:

57
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:

32
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 : 75 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 myasthenic syndrome, congenital, 1a, slow-channel and congenital myasthenic syndrome with episodic apnea, and has symptoms including apnea, respiratory distress and ophthalmoparesis. An important gene associated with Myasthenic Syndrome, Congenital, 6, Presynaptic is CHAT (Choline O-Acetyltransferase). Affiliated tissues include testes, and related phenotypes are strabismus and ptosis

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. 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:

57
Head And Neck Eyes:
ptosis
strabismus
ophthalmoparesis

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

Muscle Soft Tissue:
muscle biopsy shows type 2 fiber atrophy

Skeletal:
arthrogryposis multiplex in severe cases

Abdomen Gastrointestinal:
dysphagia
poor suck
poor feeding due to muscle weakness

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:

32 (show all 18)
# 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 weak cry 32 HP:0001612
6 dysphagia 32 HP:0002015
7 poor suck 32 HP:0002033
8 respiratory distress 32 HP:0002098
9 abnormality of the immune system 32 HP:0002715
10 respiratory insufficiency due to muscle weakness 32 HP:0002747
11 arthrogryposis multiplex congenita 32 HP:0002804
12 apneic episodes precipitated by illness, fatigue, stress 32 HP:0002872
13 sudden episodic apnea 32 HP:0002882
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

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


apnea, respiratory distress, ophthalmoparesis

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 29 CHAT

Anatomical Context for Myasthenic Syndrome, Congenital, 6, Presynaptic

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

41
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
2
Familial infantile myasthenia. ( 6243929 )
1980

Variations for Myasthenic Syndrome, Congenital, 6, Presynaptic

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

75
# Symbol AA change Variation ID SNP ID
1 CHAT p.Leu210Pro VAR_011666 rs121912820
2 CHAT p.Pro211Ala VAR_011667 rs121912815
3 CHAT p.Ile305Thr VAR_011668 rs75466054
4 CHAT p.Arg420Cys VAR_011669 rs121912822
5 CHAT p.Glu441Lys VAR_011670 rs121912816
6 CHAT p.Arg482Gly VAR_011671 rs121912818
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 top 50) (show all 127)
# 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.631C> G (p.Pro211Ala) single nucleotide variant Pathogenic rs121912815 GRCh38 Chromosome 10, 49620546: 49620546
4 CHAT NM_020549.4(CHAT): c.1321G> A (p.Glu441Lys) single nucleotide variant Pathogenic rs121912816 GRCh37 Chromosome 10, 50856592: 50856592
5 CHAT NM_020549.4(CHAT): c.1321G> A (p.Glu441Lys) single nucleotide variant Pathogenic rs121912816 GRCh38 Chromosome 10, 49648546: 49648546
6 CHAT NM_020549.4(CHAT): c.1516G> T (p.Val506Leu) single nucleotide variant Pathogenic rs121912817 GRCh37 Chromosome 10, 50859934: 50859934
7 CHAT NM_020549.4(CHAT): c.1516G> T (p.Val506Leu) single nucleotide variant Pathogenic rs121912817 GRCh38 Chromosome 10, 49651888: 49651888
8 CHAT NM_020549.4(CHAT): c.1444A> G (p.Arg482Gly) single nucleotide variant Pathogenic rs121912818 GRCh37 Chromosome 10, 50857615: 50857615
9 CHAT NM_020549.4(CHAT): c.1444A> G (p.Arg482Gly) single nucleotide variant Pathogenic rs121912818 GRCh38 Chromosome 10, 49649569: 49649569
10 CHAT NM_020549.4(CHAT): c.1679G> A (p.Arg560His) single nucleotide variant Pathogenic rs121912819 GRCh37 Chromosome 10, 50863185: 50863185
11 CHAT NM_020549.4(CHAT): c.1679G> A (p.Arg560His) single nucleotide variant Pathogenic rs121912819 GRCh38 Chromosome 10, 49655139: 49655139
12 CHAT NM_020549.4(CHAT): c.629T> C (p.Leu210Pro) single nucleotide variant Pathogenic rs121912820 GRCh37 Chromosome 10, 50828590: 50828590
13 CHAT NM_020549.4(CHAT): c.629T> C (p.Leu210Pro) single nucleotide variant Pathogenic rs121912820 GRCh38 Chromosome 10, 49620544: 49620544
14 CHAT NM_020549.4(CHAT): c.1493C> T (p.Ser498Leu) single nucleotide variant Pathogenic rs121912821 GRCh37 Chromosome 10, 50857664: 50857664
15 CHAT NM_020549.4(CHAT): c.1493C> T (p.Ser498Leu) single nucleotide variant Pathogenic rs121912821 GRCh38 Chromosome 10, 49649618: 49649618
16 CHAT NM_020549.4(CHAT): c.914T> C (p.Ile305Thr) single nucleotide variant Pathogenic rs75466054 GRCh37 Chromosome 10, 50833680: 50833680
17 CHAT NM_020549.4(CHAT): c.914T> C (p.Ile305Thr) single nucleotide variant Pathogenic rs75466054 GRCh38 Chromosome 10, 49625634: 49625634
18 CHAT NM_020549.4(CHAT): c.1258C> T (p.Arg420Cys) single nucleotide variant Pathogenic rs121912822 GRCh37 Chromosome 10, 50854697: 50854697
19 CHAT NM_020549.4(CHAT): c.1258C> T (p.Arg420Cys) single nucleotide variant Pathogenic rs121912822 GRCh38 Chromosome 10, 49646651: 49646651
20 CHAT NM_020549.4(CHAT): c.1007T> C (p.Ile336Thr) single nucleotide variant Pathogenic rs121912823 GRCh37 Chromosome 10, 50835727: 50835727
21 CHAT NM_020549.4(CHAT): c.1007T> C (p.Ile336Thr) single nucleotide variant Pathogenic rs121912823 GRCh38 Chromosome 10, 49627681: 49627681
22 CHAT NM_020549.4(CHAT): c.1771G> A (p.Val591Met) single nucleotide variant Uncertain significance rs201485243 GRCh37 Chromosome 10, 50863277: 50863277
23 CHAT NM_020549.4(CHAT): c.1771G> A (p.Val591Met) single nucleotide variant Uncertain significance rs201485243 GRCh38 Chromosome 10, 49655231: 49655231
24 CHAT NM_020549.4(CHAT): c.1883G> A (p.Arg628Gln) single nucleotide variant Uncertain significance rs114545628 GRCh37 Chromosome 10, 50870734: 50870734
25 CHAT NM_020549.4(CHAT): c.1883G> A (p.Arg628Gln) single nucleotide variant Uncertain significance rs114545628 GRCh38 Chromosome 10, 49662688: 49662688
26 CHAT NM_020549.4(CHAT): c.418C> T (p.Gln140Ter) single nucleotide variant Pathogenic rs794727516 GRCh37 Chromosome 10, 50827801: 50827801
27 CHAT NM_020549.4(CHAT): c.418C> T (p.Gln140Ter) single nucleotide variant Pathogenic rs794727516 GRCh38 Chromosome 10, 49619755: 49619755
28 CHAT NM_020549.4(CHAT): c.1248C> T (p.Asn416=) single nucleotide variant Conflicting interpretations of pathogenicity rs116071049 GRCh37 Chromosome 10, 50854687: 50854687
29 CHAT NM_020549.4(CHAT): c.1248C> T (p.Asn416=) single nucleotide variant Conflicting interpretations of pathogenicity rs116071049 GRCh38 Chromosome 10, 49646641: 49646641
30 CHAT NM_020549.4(CHAT): c.1372C> T (p.Leu458Phe) single nucleotide variant Benign rs76014951 GRCh37 Chromosome 10, 50856643: 50856643
31 CHAT NM_020549.4(CHAT): c.1372C> T (p.Leu458Phe) single nucleotide variant Benign rs76014951 GRCh38 Chromosome 10, 49648597: 49648597
32 CHAT NM_020549.4(CHAT): c.745C> G (p.Leu249Val) single nucleotide variant Benign/Likely benign rs115510708 GRCh37 Chromosome 10, 50830189: 50830189
33 CHAT NM_020549.4(CHAT): c.745C> G (p.Leu249Val) single nucleotide variant Benign/Likely benign rs115510708 GRCh38 Chromosome 10, 49622143: 49622143
34 CHAT NM_020549.4(CHAT): c.327G> A (p.Thr109=) single nucleotide variant Benign/Likely benign rs79914771 GRCh37 Chromosome 10, 50824588: 50824588
35 CHAT NM_020549.4(CHAT): c.327G> A (p.Thr109=) single nucleotide variant Benign/Likely benign rs79914771 GRCh38 Chromosome 10, 49616542: 49616542
36 CHAT NM_020549.4(CHAT): c.438C> T (p.Tyr146=) single nucleotide variant Benign rs61731734 GRCh38 Chromosome 10, 49619775: 49619775
37 CHAT NM_020549.4(CHAT): c.438C> T (p.Tyr146=) single nucleotide variant Benign rs61731734 GRCh37 Chromosome 10, 50827821: 50827821
38 CHAT NM_020549.4(CHAT): c.896C> T (p.Pro299Leu) single nucleotide variant Benign/Likely benign rs868749 GRCh37 Chromosome 10, 50833662: 50833662
39 CHAT NM_020549.4(CHAT): c.896C> T (p.Pro299Leu) single nucleotide variant Benign/Likely benign rs868749 GRCh38 Chromosome 10, 49625616: 49625616
40 CHAT NM_020549.4(CHAT): c.1135G> C (p.Asp379His) single nucleotide variant Benign/Likely benign rs115212829 GRCh37 Chromosome 10, 50854574: 50854574
41 CHAT NM_020549.4(CHAT): c.1135G> C (p.Asp379His) single nucleotide variant Benign/Likely benign rs115212829 GRCh38 Chromosome 10, 49646528: 49646528
42 CHAT NM_020549.4(CHAT): c.2178G> A (p.Pro726=) single nucleotide variant Likely benign rs77144546 GRCh37 Chromosome 10, 50873023: 50873023
43 CHAT NM_020549.4(CHAT): c.2178G> A (p.Pro726=) single nucleotide variant Likely benign rs77144546 GRCh38 Chromosome 10, 49664977: 49664977
44 CHAT NM_020549.4(CHAT): c.85A> T (p.Arg29Ter) single nucleotide variant Pathogenic rs772025588 GRCh37 Chromosome 10, 50822320: 50822320
45 CHAT NM_020549.4(CHAT): c.85A> T (p.Arg29Ter) single nucleotide variant Pathogenic rs772025588 GRCh38 Chromosome 10, 49614274: 49614274
46 CHAT NM_020549.4(CHAT): c.2222G> A (p.Arg741Lys) single nucleotide variant Uncertain significance rs114719193 GRCh37 Chromosome 10, 50873067: 50873067
47 CHAT NM_020549.4(CHAT): c.2222G> A (p.Arg741Lys) single nucleotide variant Uncertain significance rs114719193 GRCh38 Chromosome 10, 49665021: 49665021
48 CHAT NM_020549.4(CHAT): c.620G> A (p.Arg207His) single nucleotide variant Pathogenic/Likely pathogenic rs764497513 GRCh37 Chromosome 10, 50828581: 50828581
49 CHAT NM_020549.4(CHAT): c.620G> A (p.Arg207His) single nucleotide variant Pathogenic/Likely pathogenic rs764497513 GRCh38 Chromosome 10, 49620535: 49620535
50 CHAT NM_020549.4(CHAT): c.2177C> T (p.Pro726Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs79414242 GRCh37 Chromosome 10, 50873022: 50873022

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 multicellular organism development GO:0007275 9.55 ANGPTL6 FGFR1 ZMYM2 ZMYM3 ZMYM6
2 photoreceptor cell maintenance GO:0045494 9.26 BBS2 TULP1
3 cytoskeleton organization GO:0007010 9.13 ZMYM2 ZMYM3 ZMYM6
4 regulation of cell morphogenesis GO:0022604 8.8 ZMYM2 ZMYM3 ZMYM6

Sources for Myasthenic Syndrome, Congenital, 6, Presynaptic

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