CMS
MCID: CNG001
MIFTS: 63

Congenital Myasthenic Syndrome (CMS)

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

Aliases & Classifications for Congenital Myasthenic Syndrome

MalaCards integrated aliases for Congenital Myasthenic Syndrome:

Name: Congenital Myasthenic Syndrome 12 53 25 59 37 29 6 15
Congenital Myasthenia 24 53 25 54
Cms 53 25 59
Myasthenic Syndromes, Congenital 44 72
Congenital Myasthenic Syndromes 24 25
Congenital Myasthenic Syndrome Ib 72
Syndrome, Myasthenic, Congenital 40
Myasthenic Syndromes Congenital 55
Myasthenia - Congenital 54

Characteristics:

Orphanet epidemiological data:

59
congenital myasthenic syndrome
Inheritance: Autosomal dominant,Autosomal recessive; Prevalence: 1-9/1000000 (Europe),1-9/1000000 (United Kingdom); Age of onset: Infancy,Neonatal; Age of death: any age;

GeneReviews:

24
Penetrance In general, reported cms pathogenic variants have complete penetrance....

Classifications:



External Ids:

Disease Ontology 12 DOID:3635
KEGG 37 H00770
MeSH 44 D020294
NCIt 50 C84647
MESH via Orphanet 45 D020294
ICD10 via Orphanet 34 G70.2
UMLS via Orphanet 73 C0751882
Orphanet 59 ORPHA590
UMLS 72 C0751882 C1850792

Summaries for Congenital Myasthenic Syndrome

NINDS : 54 All forms of myasthenia are due to problems in the communication between nerve cells and muscles. Most involve the activities of neurotransmitters. Neurotransmitters are chemicals that allow neurons to relay information from one cell to the next. For neurotransmitters to be effective, the nerve cell must release the neurotransmitter properly, and the muscle cell must be able to detect the neurotransmitter and respond to its signal properly. The most common type of myasthenia, myasthenia gravis, is caused by an abnormal immune response in which antibodies block the ability of the muscle to detect the neurotransmitter. Congenital myasthenia, however, differs from myasthenia gravis because the disrupted communication isn't caused by antibodies, but by genetic defects. There are several different subtypes of congenital myasthenia, each the result of a specific genetic mutation. Since all types of myasthenia are due to the inability of nerves to trigger muscle activity, they all involve weakness, although there is some variability in the specific muscles affected. Symptoms of congenital myasthenia usually appear in the first few years of childhood, but may not be noticeable until much later, occasionally remaining unrecognized until adulthood. If the symptoms begin in infancy, they usually appear as "floppiness" and a failure to meet developmental milestones, such as rolling over or sitting up. Some infants may also have episodes of choking or pauses in breathing. If the symptoms begin in toddlers or preschool children, they appear as weakness during physical activities or an inability to perform age-appropriate actions, such as running or climbing. In addition, if eye muscles are involved, children may have droopy eyelids, "lazy eye," or double vision. If mouth or throat muscles are involved, children may have difficulty speaking or swallowing. An important characteristic of myasthenia is that the weakness worsens during continuous activity, with strength returning, at least partially, after resting. Congenital myasthenia is an inherited (genetic) disorder. All but one known subtype are recessive disorders, which means that a child will have to have two copies of the abnormal gene (one from each parent) in order to develop the disease. To diagnose congenital myasthenia, a neurologist will test various muscles to determine if they grow weaker with repeated activity. The doctor will also test the electrical activity of nerves and muscles using electromyography (EMG) and nerve conduction tests (NCS). Blood tests are often used to determine if antibodies could be causing the symptoms. Genetic tests may be ordered.

MalaCards based summary : Congenital Myasthenic Syndrome, also known as congenital myasthenia, is related to slow-channel congenital myasthenic syndrome and myasthenic syndrome, congenital, 4c, associated with acetylcholine receptor deficiency, and has symptoms including facial paresis An important gene associated with Congenital Myasthenic Syndrome is CHRNE (Cholinergic Receptor Nicotinic Epsilon Subunit), and among its related pathways/superpathways are Neuroactive ligand-receptor interaction and Glycerophospholipid metabolism. The drugs Ephedrine and Pseudoephedrine have been mentioned in the context of this disorder. Affiliated tissues include eye, skeletal muscle and skin, and related phenotypes are ptosis and dysphagia

Disease Ontology : 12 A neuromuscular junction disease that is characterized by weakness and easy fatiguability resulting from a genetic defect at the junction where the nerve stimulates muscle activity that result in muscle weakness and may affect nerve cells (presynaptic), muscle cells (postsynaptic) or the space between nerve and muscle cells (synaptic).

Genetics Home Reference : 25 Congenital myasthenic syndrome is a group of conditions characterized by muscle weakness (myasthenia) that worsens with physical exertion. The muscle weakness typically begins in early childhood but can also appear in adolescence or adulthood. Facial muscles, including muscles that control the eyelids, muscles that move the eyes, and muscles used for chewing and swallowing, are most commonly affected. However, any of the muscles used for movement (skeletal muscles) can be affected in this condition. Due to muscle weakness, affected infants may have feeding difficulties. Development of motor skills such as crawling or walking may be delayed. The severity of the myasthenia varies greatly, with some people experiencing minor weakness and others having such severe weakness that they are unable to walk. Some individuals have episodes of breathing problems that may be triggered by fevers or infection. Severely affected individuals may also experience short pauses in breathing (apnea) that can lead to a bluish appearance of the skin or lips (cyanosis).

NIH Rare Diseases : 53 Congenital myasthenic syndrome (CMS) is a group of genetic disorders that result in muscle weakness and fatigue. Symptoms can range from mild weakness to progressive disabling weakness. There are three main subtypes of CMS, which are defined by how they affect the connection between muscles and the nervous system: postsynaptic (75-80% of patients), synaptic (14-15% of patients), and presynaptic (7-8% of patients). Identification of the specific subtype is important in patient care for determining the most effective treatment. Mutations in many genes have been found to cause CMS, and most forms of CMS are inherited in an autosomal recessive pattern. One form of CMS, a postsynaptic form known as slow-channel syndrome congenital myasthenic syndrome is inherited in an autosomal dominant manner.

KEGG : 37
Congenital myasthenic syndromes (CMS) are a heterogenous group of genetic disorders caused by mutations in several proteins that compose the neuromuscular junction (NMJ) apparatus on which synaptic formation and function depend. The majority are recessively inherited. The disorders of the NMJ cause weakness and fatigue.

Wikipedia : 75 Congenital myasthenic syndrome (CMS) is an inherited neuromuscular disorder caused by defects of several... more...

GeneReviews: NBK1168

Related Diseases for Congenital Myasthenic Syndrome

Diseases in the Congenital Myasthenic Syndrome family:

Myasthenic Syndrome, Congenital, 10 Myasthenic Syndrome, Congenital, 5
Myasthenic Syndrome, Congenital, 12 Myasthenic Syndrome, Congenital, 16
Myasthenic Syndrome, Congenital, 13 Myasthenic Syndrome, Congenital, 8
Myasthenic Syndrome, Congenital, 22 Myasthenic Syndrome, Congenital, 15
Myasthenic Syndrome, Congenital, 14 Myasthenic Syndrome, Congenital, 17
Myasthenic Syndrome, Congenital, 18 Myasthenic Syndrome, Congenital, 19

Diseases related to Congenital Myasthenic Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 815)
# Related Disease Score Top Affiliating Genes
1 slow-channel congenital myasthenic syndrome 34.9 CHRNE CHRND CHRNB1 CHRNA1
2 myasthenic syndrome, congenital, 4c, associated with acetylcholine receptor deficiency 34.8 MUSK DOK7 CHRNE
3 congenital myasthenic syndrome with episodic apnea 34.7 SLC5A7 CHAT
4 myasthenic syndrome, congenital, 5 34.7 DPAGT1 COLQ ACHE
5 congenital myasthenic syndrome associated with acetylcholine receptor deficiency 34.6 GFPT1 CHRNE
6 congenital myasthenic syndromes with glycosylation defect 34.6 GMPPB GFPT1 DPAGT1 ALG14
7 myasthenic syndrome, congenital, 1b, fast-channel 34.6 CHRNE CHRNA1
8 postsynaptic congenital myasthenic syndromes 34.5 SCN4A RAPSN MUSK DOK7 CHRNE CHRND
9 presynaptic congenital myasthenic syndromes 34.4 VAMP1 SLC5A7 SLC25A1 MYO9A CHAT AGRN
10 myasthenic syndrome, congenital, 6, presynaptic 34.0 DPAGT1 CHAT
11 ptosis 31.9 RAPSN MUSK DOK7 COLQ CHRNE CHRND
12 myasthenia gravis 31.8 RAPSN MUSK CHRNE CHRNA1 AGRN ACHE
13 myopathy, tubular aggregate, 1 30.9 GFPT1 DPAGT1 DOK7
14 muscular disease 30.9 SCN4A GMPPB DOK7 AGRN
15 neonatal myasthenia gravis 30.8 MUSK DPAGT1
16 sclerosteosis 2 30.6 RAPSN MUSK DPAGT1 DOK7 AGRN
17 cenani-lenz syndactyly syndrome 30.4 SCN4A RAPSN MUSK DPAGT1 DOK7 CHAT
18 peripheral nervous system disease 30.2 RAPSN MUSK DPAGT1 DOK7 COLQ CHRNE
19 myasthenic syndrome, congenital, 1a, slow-channel 12.4
20 myasthenic syndrome, congenital, 10 12.3
21 myasthenic syndrome, congenital, 16 12.3
22 myasthenic syndrome, congenital, 4a, slow-channel 12.3
23 myasthenic syndrome, congenital, 8 12.3
24 myasthenic syndrome, congenital, 13 12.3
25 myasthenic syndrome, congenital, 11, associated with acetylcholine receptor deficiency 12.3
26 myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency 12.2
27 myasthenic syndrome, congenital, 7, presynaptic 12.2
28 myasthenic syndrome, congenital, 14 12.2
29 capillary malformation-arteriovenous malformation 1 12.2
30 myasthenic syndrome, congenital, 4b, fast-channel 12.2
31 myasthenic syndrome, congenital, 3b, fast-channel 12.2
32 myasthenic syndrome, congenital, 3c, associated with acetylcholine receptor deficiency 12.2
33 myasthenic syndrome, congenital, 12 12.2
34 myasthenic syndrome, congenital, 2c, associated with acetylcholine receptor deficiency 12.2
35 myasthenic syndrome, congenital, 3a, slow-channel 12.2
36 myasthenic syndrome, congenital, 15 12.1
37 myasthenic syndrome, congenital, 20, presynaptic 12.1
38 myasthenic syndrome, congenital, 21, presynaptic 12.1
39 myasthenic syndrome, congenital, 17 12.1
40 myasthenic syndrome, congenital, 19 12.1
41 myasthenic syndrome, congenital, 22 12.1
42 myasthenic syndrome, congenital, 18 12.1
43 myasthenic syndrome, congenital, 2a, slow-channel 11.7
44 chronic mountain sickness 11.7
45 megalencephaly-capillary malformation-polymicrogyria syndrome 11.6
46 myasthenic syndrome, congenital, 25, presynaptic 11.5
47 chiari malformation 11.5
48 myasthenic syndrome, congenital, 24, presynaptic 11.5
49 muscular dystrophy-dystroglycanopathy , type c, 14 11.5
50 myasthenic syndrome, congenital, 23, presynaptic 11.5

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



Diseases related to Congenital Myasthenic Syndrome

Symptoms & Phenotypes for Congenital Myasthenic Syndrome

Human phenotypes related to Congenital Myasthenic Syndrome:

59 32 (show top 50) (show all 68)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ptosis 59 32 hallmark (90%) Very frequent (99-80%) HP:0000508
2 dysphagia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002015
3 proximal muscle weakness 59 32 hallmark (90%) Very frequent (99-80%) HP:0003701
4 neck muscle weakness 59 32 hallmark (90%) Very frequent (99-80%) HP:0000467
5 fatigable weakness 59 32 hallmark (90%) Very frequent (99-80%) HP:0003473
6 poor suck 59 32 hallmark (90%) Very frequent (99-80%) HP:0002033
7 sudden episodic apnea 59 32 hallmark (90%) Very frequent (99-80%) HP:0002882
8 intermittent episodes of respiratory insufficiency due to muscle weakness 59 32 hallmark (90%) Very frequent (99-80%) HP:0004889
9 frontalis muscle weakness 59 32 hallmark (90%) Very frequent (99-80%) HP:0004661
10 intellectual disability 59 32 frequent (33%) Frequent (79-30%) HP:0001249
11 ataxia 59 32 frequent (33%) Frequent (79-30%) HP:0001251
12 recurrent respiratory infections 59 32 frequent (33%) Frequent (79-30%) HP:0002205
13 generalized muscle weakness 59 32 frequent (33%) Frequent (79-30%) HP:0003324
14 arthrogryposis multiplex congenita 59 32 frequent (33%) Frequent (79-30%) HP:0002804
15 easy fatigability 59 32 frequent (33%) Frequent (79-30%) HP:0003388
16 ophthalmoplegia 59 32 frequent (33%) Frequent (79-30%) HP:0000602
17 nasal speech 59 32 frequent (33%) Frequent (79-30%) HP:0001611
18 difficulty walking 59 32 frequent (33%) Frequent (79-30%) HP:0002355
19 decreased fetal movement 59 32 frequent (33%) Frequent (79-30%) HP:0001558
20 muscle fiber atrophy 59 32 frequent (33%) Frequent (79-30%) HP:0100295
21 cyanosis 59 32 frequent (33%) Frequent (79-30%) HP:0000961
22 bulbar palsy 59 32 frequent (33%) Frequent (79-30%) HP:0001283
23 spinal deformities 59 32 frequent (33%) Frequent (79-30%) HP:0008443
24 episodic respiratory distress 59 32 frequent (33%) Frequent (79-30%) HP:0004885
25 choking episodes 59 32 frequent (33%) Frequent (79-30%) HP:0030842
26 central sleep apnea 59 32 frequent (33%) Frequent (79-30%) HP:0010536
27 emg: impaired neuromuscular transmission 59 32 frequent (33%) Frequent (79-30%) HP:0100285
28 apneic episodes precipitated by illness, fatigue, stress 59 32 frequent (33%) Frequent (79-30%) HP:0002872
29 nasal regurgitation 59 32 frequent (33%) Frequent (79-30%) HP:0011469
30 high palate 59 32 occasional (7.5%) Occasional (29-5%) HP:0000218
31 seizures 59 32 occasional (7.5%) Occasional (29-5%) HP:0001250
32 dysphonia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001618
33 areflexia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001284
34 pes cavus 59 32 occasional (7.5%) Occasional (29-5%) HP:0001761
35 waddling gait 59 32 occasional (7.5%) Occasional (29-5%) HP:0002515
36 spinal rigidity 59 32 occasional (7.5%) Occasional (29-5%) HP:0003306
37 emg: myopathic abnormalities 59 32 occasional (7.5%) Occasional (29-5%) HP:0003458
38 toe walking 59 32 occasional (7.5%) Occasional (29-5%) HP:0040083
39 motor delay 59 32 occasional (7.5%) Occasional (29-5%) HP:0001270
40 kyphoscoliosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0002751
41 long face 59 32 occasional (7.5%) Occasional (29-5%) HP:0000276
42 weak cry 59 32 occasional (7.5%) Occasional (29-5%) HP:0001612
43 distal amyotrophy 59 32 occasional (7.5%) Occasional (29-5%) HP:0003693
44 limb-girdle muscle weakness 59 32 occasional (7.5%) Occasional (29-5%) HP:0003325
45 distal lower limb muscle weakness 59 32 occasional (7.5%) Occasional (29-5%) HP:0009053
46 poor head control 59 32 occasional (7.5%) Occasional (29-5%) HP:0002421
47 stridor 59 32 occasional (7.5%) Occasional (29-5%) HP:0010307
48 central hypotonia 59 32 occasional (7.5%) Occasional (29-5%) HP:0011398
49 narrow jaw 59 32 occasional (7.5%) Occasional (29-5%) HP:0012801
50 low-set ears 59 32 very rare (1%) Very rare (<4-1%) HP:0000369

UMLS symptoms related to Congenital Myasthenic Syndrome:


facial paresis

MGI Mouse Phenotypes related to Congenital Myasthenic Syndrome:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 mortality/aging MP:0010768 10.07 ACHE AGRN CHAT CHRNA1 CHRNE DOK7
2 behavior/neurological MP:0005386 10.06 ACHE AGRN CHAT CHRNA1 CHRNE DOK7
3 muscle MP:0005369 9.76 ACHE AGRN CHAT CHRNE DOK7 MUSK
4 nervous system MP:0003631 9.7 ACHE AGRN CHAT CHRNA1 CHRNB1 CHRNE
5 respiratory system MP:0005388 9.28 ACHE AGRN CHAT CHRNE DOK7 MUSK

Drugs & Therapeutics for Congenital Myasthenic Syndrome

Drugs for Congenital Myasthenic Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 21)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Ephedrine Approved Phase 1, Phase 2 299-42-3 9294
2
Pseudoephedrine Approved Phase 1, Phase 2 90-82-4 7028
3 Neurotransmitter Agents Phase 1, Phase 2
4 Respiratory System Agents Phase 1, Phase 2
5 Adrenergic Agents Phase 1, Phase 2
6 Anti-Asthmatic Agents Phase 1, Phase 2
7 Autonomic Agents Phase 1, Phase 2
8 Bronchodilator Agents Phase 1, Phase 2
9 Sympathomimetics Phase 1, Phase 2
10 Central Nervous System Stimulants Phase 1, Phase 2
11 Nasal Decongestants Phase 1, Phase 2
12 Vasoconstrictor Agents Phase 1, Phase 2
13 Adrenergic Agonists Phase 1
14 Adrenergic beta-Agonists Phase 1
15 Tocolytic Agents Phase 1
16 Adrenergic beta-2 Receptor Agonists Phase 1
17 Albuterol Phase 1
18
Amifampridine Approved, Investigational 54-96-6
19 Neuromuscular Agents
20 Peripheral Nervous System Agents
21 Potassium Channel Blockers

Interventional clinical trials:

(show all 12)
# Name Status NCT ID Phase Drugs
1 A Phase 3, Double-blind, Outpatient Crossover Study to Evaluate the Efficacy and Safety of Amifampridine Phosphate (3,4 Diaminopyridine Phosphate) in Patients With Congenital Myasthenic Syndromes (CMS) Recruiting NCT02562066 Phase 3 amifampridine phosphate;Placebo
2 Ephedrine for the Treatment of Congenital Myasthenia Unknown status NCT00541216 Phase 1, Phase 2 Ephedrine
3 Efficacy of Albuterol in the Treatment of Congenital Myasthenic Syndromes Completed NCT01203592 Phase 1 Albuterol
4 Retrospective Study :Describe the Changes of the Disease in Many Cases Likely to Aggravate. Completed NCT01474980
5 Open Label Trial Of 3,4-Diaminopyridine In Lambert-Eaton Myasthenic Syndrome (LEMS) and Congenital Myasthenic Syndromes (CMS) Recruiting NCT00872950 3,4-DIAMINOPYRIDINE;3,4-Diaminopyridine
6 Congenital Muscle Disease Patient and Proxy Reported Outcome Study Recruiting NCT01403402
7 National Registry for Egyptian Pediatric Neuromuscular Diseases Recruiting NCT02124616
8 An Open-Label, Expanded Access Protocol for Amifampridine Phosphate Treatment in Patients With Congenital Myasthenic Syndrome (CMS) Available NCT02189720 Amifampridine Phosphate
9 Treatment Use of 3,4 Diaminopyridine in Congenital Myasthenia and Lambert-Eaton Syndrome Available NCT03062631 3,4-Diaminopyridine
10 3,4-Diaminopyridine for Lambert-Eaton Myasthenic Syndrome and Congenital Myasthenia Available NCT02012933 3,4-diaminopyridine
11 Treatment Use of 3,4-Diaminopyridine in Lambert-Eaton Myasthenia and Congenital Myasthenia Gravis No longer available NCT01765140 3,4-diaminopyridine;3,4-diaminopyridine
12 Treatment of Lambert-Eaton Myasthenic Syndrome and Congenital Myasthenic Syndromes With 3, 4-Diaminopyridine No longer available NCT01378546 3,4-diaminopyridine

Search NIH Clinical Center for Congenital Myasthenic Syndrome

Cochrane evidence based reviews: myasthenic syndromes, congenital

Genetic Tests for Congenital Myasthenic Syndrome

Genetic tests related to Congenital Myasthenic Syndrome:

# Genetic test Affiliating Genes
1 Congenital Myasthenic Syndrome 29 MYO9A SLC25A1 SLC5A7

Anatomical Context for Congenital Myasthenic Syndrome

MalaCards organs/tissues related to Congenital Myasthenic Syndrome:

41
Eye, Skeletal Muscle, Skin, Testes, Brain, Bone, Thymus

Publications for Congenital Myasthenic Syndrome

Articles related to Congenital Myasthenic Syndrome:

(show top 50) (show all 606)
# Title Authors PMID Year
1
Mutations in MUSK causing congenital myasthenic syndrome impair MuSK-Dok-7 interaction. 9 38 4 71
20371544 2010
2
CHRND mutation causes a congenital myasthenic syndrome by impairing co-clustering of the acetylcholine receptor with rapsyn. 9 38 4 71
16916845 2006
3
Congenital myasthenic syndromes. 9 38 4 71
15367858 2004
4
Mutation in the human acetylcholinesterase-associated collagen gene, COLQ, is responsible for congenital myasthenic syndrome with end-plate acetylcholinesterase deficiency (Type Ic). 9 38 4 71
9758617 1998
5
Human endplate acetylcholinesterase deficiency caused by mutations in the collagen-like tail subunit (ColQ) of the asymmetric enzyme. 9 38 4 71
9689136 1998
6
Congenital Myasthenic Syndrome Type 19 Is Caused by Mutations in COL13A1, Encoding the Atypical Non-fibrillar Collagen Type XIII α1 Chain. 38 4 71
26626625 2015
7
Clinical and pathological heterogeneity of a congenital disorder of glycosylation manifesting as a myasthenic/myopathic syndrome. 38 4 71
24461433 2014
8
LRP4 third β-propeller domain mutations cause novel congenital myasthenia by compromising agrin-mediated MuSK signaling in a position-specific manner. 38 4 71
24234652 2014
9
Congenital myasthenic syndromes due to mutations in ALG2 and ALG14. 38 4 71
23404334 2013
10
LG2 agrin mutation causing severe congenital myasthenic syndrome mimics functional characteristics of non-neural (z-) agrin. 38 4 71
22205389 2012
11
Mutations in DPAGT1 cause a limb-girdle congenital myasthenic syndrome with tubular aggregates. 38 4 71
22742743 2012
12
Identification of an agrin mutation that causes congenital myasthenia and affects synapse function. 38 4 71
19631309 2009
13
Mutation analysis of CHRNA1, CHRNB1, CHRND, and RAPSN genes in multiple pterygium syndrome/fetal akinesia patients. 38 4 71
18179903 2008
14
MUSK, a new target for mutations causing congenital myasthenic syndrome. 38 4 71
15496425 2004
15
Mutation history of the roma/gypsies. 38 4 71
15322984 2004
16
The congenital myasthenic syndrome mutation RAPSN N88K derives from an ancient Indo-European founder. 38 4 71
15286164 2004
17
E-box mutations in the RAPSN promoter region in eight cases with congenital myasthenic syndrome. 38 4 71
12651869 2003
18
Choline acetyltransferase mutations cause myasthenic syndrome associated with episodic apnea in humans. 38 4 71
11172068 2001
19
Mutation causing congenital myasthenia reveals acetylcholine receptor beta/delta subunit interaction essential for assembly. 38 4 71
10562302 1999
20
A common mutation (epsilon1267delG) in congenital myasthenic patients of Gypsy ethnic origin. 38 4 71
10534268 1999
21
Mutation of the acetylcholine receptor epsilon-subunit promoter in congenital myasthenic syndrome. 38 4 71
10211467 1999
22
Mutations in different functional domains of the human muscle acetylcholine receptor alpha subunit in patients with the slow-channel congenital myasthenic syndrome. 38 4 71
9158151 1997
23
Mutant SNAP25B causes myasthenia, cortical hyperexcitability, ataxia, and intellectual disability. 4 71
25381298 2014
24
Synaptotagmin 2 mutations cause an autosomal-dominant form of lambert-eaton myasthenic syndrome and nonprogressive motor neuropathy. 4 71
25192047 2014
25
Hexosamine biosynthetic pathway mutations cause neuromuscular transmission defect. 4 71
21310273 2011
26
Refinement of the clinical phenotype in musk-related congenital myasthenic syndromes. 4 71
19949040 2009
27
Congenital myasthenic syndrome caused by two non-N88K rapsyn mutations. 9 38 71
17594401 2007
28
Impaired receptor clustering in congenital myasthenic syndrome with novel RAPSN mutations. 9 38 71
16931511 2006
29
Dok-7 mutations underlie a neuromuscular junction synaptopathy. 4 71
16917026 2006
30
Regulation of the rapsyn promoter by kaiso and delta-catenin. 9 38 71
15282317 2004
31
Rapsyn mutations in hereditary myasthenia: distinct early- and late-onset phenotypes. 4 71
14504330 2003
32
Myasthenic syndrome caused by mutation of the SCN4A sodium channel. 4 71
12766226 2003
33
Congenital myasthenic syndrome with episodic apnea in patients homozygous for a CHAT missense mutation. 9 38 71
12756141 2003
34
Identification of pathogenic mutations in the human rapsyn gene. 9 38 71
12730725 2003
35
Recessive inheritance and variable penetrance of slow-channel congenital myasthenic syndromes. 4 71
12141316 2002
36
Rapsyn mutations in humans cause endplate acetylcholine-receptor deficiency and myasthenic syndrome. 4 71
11791205 2002
37
Acetylcholine receptor delta subunit mutations underlie a fast-channel myasthenic syndrome and arthrogryposis multiplex congenita. 4 71
11435464 2001
38
Immature end-plates and utrophin deficiency in congenital myasthenic syndrome caused by epsilon-AChR subunit truncating mutations. 9 38 71
11030414 2000
39
Leukoencephalopathy due to variants in GFPT1-associated congenital myasthenic syndrome. 38 71
30635494 2019
40
Defective fast inactivation recovery of Nav 1.4 in congenital myasthenic syndrome. 38 71
25707578 2015
41
Use of next-generation sequencing as a diagnostic tool for congenital myasthenic syndrome. 38 71
25194721 2014
42
Highly fatal fast-channel syndrome caused by AChR ε subunit mutation at the agonist binding site. 38 71
22592360 2012
43
Germline mutation in DOK7 associated with fetal akinesia deformation sequence. 38 71
19261599 2009
44
The CHRNE 1293insG founder mutation is a frequent cause of congenital myasthenia in North Africa. 38 71
19064877 2008
45
hnRNP H enhances skipping of a nonfunctional exon P3A in CHRNA1 and a mutation disrupting its binding causes congenital myasthenic syndrome. 38 71
18806275 2008
46
Congenital myasthenia-related AChR delta subunit mutation interferes with intersubunit communication essential for channel gating. 38 71
18398509 2008
47
Clinical features of the DOK7 neuromuscular junction synaptopathy. 9 38 4
17452375 2007
48
An intronic base alteration of the CHRNE gene leading to a congenital myasthenic syndrome. 38 71
16087917 2005
49
Congenital endplate acetylcholinesterase deficiency responsive to ephedrine. 9 38 4
16009904 2005
50
A newly identified chromosomal microdeletion of the rapsyn gene causes a congenital myasthenic syndrome. 9 38 4
15482960 2004

Variations for Congenital Myasthenic Syndrome

ClinVar genetic disease variations for Congenital Myasthenic Syndrome:

6 (show all 35)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 AGRN NM_198576.4(AGRN): c.5179G> T (p.Val1727Phe) single nucleotide variant Pathogenic rs587777298 1:986143-986143 1:1050763-1050763
2 AGRN NM_198576.4(AGRN): c.1057C> T (p.Gln353Ter) single nucleotide variant Pathogenic rs587777299 1:976962-976962 1:1041582-1041582
3 AGRN NM_198576.4(AGRN): c.226G> A (p.Gly76Ser) single nucleotide variant Pathogenic rs756623659 1:957605-957605 1:1022225-1022225
4 AGRN NM_198576.4(AGRN): c.314A> T (p.Asn105Ile) single nucleotide variant Pathogenic rs879253787 1:957693-957693 1:1022313-1022313
5 AGRN NM_198576.4(AGRN): c.1362dup (p.Ser455fs) duplication Pathogenic rs879253788 1:977520-977520 1:1042140-1042140
6 AGRN NM_198576.4(AGRN): c.5023G> A (p.Gly1675Ser) single nucleotide variant Pathogenic rs764160563 1:985853-985853 1:1050473-1050473
7 AGRN NM_198576.4(AGRN): c.5611G> A (p.Gly1871Arg) single nucleotide variant Pathogenic rs763818876 1:987155-987155 1:1051775-1051775
8 CHRNE NM_000080.4(CHRNE): c.1353dup (p.Asn452fs) duplication Pathogenic rs773526895 17:4802160-4802160 17:4898865-4898865
9 CHRNE NM_000080.3(CHRNE): c.1327delG (p.Glu443LysfsTer64) deletion Pathogenic rs763258280 17:4802186-4802186 17:4898891-4898891
10 CHRNE NM_000080.4(CHRNE): c.130dup (p.Glu44fs) duplication Pathogenic rs762368691 17:4805975-4805975 17:4902680-4902680
11 SCN4A NM_000334.4(SCN4A): c.4360C> T (p.Arg1454Trp) single nucleotide variant Pathogenic rs879253789 17:62019282-62019282 17:63941922-63941922
12 CHRNE NC_000017.11: g.4902680_4903969del1290insTCTGGATGCG indel Pathogenic 17:4805975-4807264 17:4902680-4903969
13 AGRN 1p36.33 deletion (0.48 Mb) deletion Pathogenic
14 RAPSN NM_005055.4(RAPSN): c.-199C> G single nucleotide variant Pathogenic rs886037842 11:47470715-47470715 11:47449163-47449163
15 CHRNE NM_000080.4(CHRNE): c.1090dup (p.Arg364fs) duplication Pathogenic rs1156634884 17:4802622-4802622 17:4899327-4899327
16 GFPT1 NM_001244710.1(GFPT1): c.686-2A> G single nucleotide variant Pathogenic rs1011196447 2:69581446-69581446 2:69354314-69354314
17 VAMP1 NM_014231.5(VAMP1): c.146G> C (p.Arg49Pro) single nucleotide variant Pathogenic rs754046104 12:6575150-6575150 12:6465984-6465984
18 DOK7 NM_173660.5(DOK7): c.1124_1127dup (p.Ala378fs) duplication Pathogenic rs606231128 4:3494837-3494840 4:3493110-3493113
19 SCN4A NM_000334.4(SCN4A): c.4325T> A (p.Val1442Glu) single nucleotide variant Pathogenic rs121908553 17:62019317-62019317 17:63941957-63941957
20 RAPSN NM_005055.4(RAPSN): c.-210A> G single nucleotide variant Pathogenic rs786200905 11:47470726-47470726 11:47449174-47449174
21 CHAT NM_020549.4(CHAT): c.914T> C (p.Ile305Thr) single nucleotide variant Pathogenic rs75466054 10:50833680-50833680 10:49625634-49625634
22 AGRN NM_198576.4(AGRN): c.5125G> C (p.Gly1709Arg) single nucleotide variant Pathogenic rs199476396 1:985955-985955 1:1050575-1050575
23 CHRNE NM_000080.4(CHRNE): c.183_187dup (p.Leu63fs) duplication Pathogenic/Likely pathogenic rs776927709 17:4805918-4805922 17:4902623-4902627
24 GMPPB NM_021971.2(GMPPB): c.1000G> A (p.Asp334Asn) single nucleotide variant Pathogenic/Likely pathogenic rs397509422 3:49759268-49759268 3:49721835-49721835
25 COLQ NM_005677.4(COLQ): c.279C> A (p.Cys93Ter) single nucleotide variant Likely pathogenic 3:15529755-15529755 3:15488248-15488248
26 CHRNE NM_000080.4(CHRNE): c.1220-2A> G single nucleotide variant Conflicting interpretations of pathogenicity 17:4802404-4802404 17:4899109-4899109
27 CHRNE NM_000080.4(CHRNE): c.488C> T (p.Ser163Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs121909516 17:4805239-4805239 17:4901944-4901944
28 SCN4A NM_000334.4(SCN4A): c.737C> T (p.Ser246Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs80338951 17:62045682-62045682 17:63968322-63968322
29 RAPSN NM_005055.5(RAPSN): c.264C> A (p.Asn88Lys) single nucleotide variant Conflicting interpretations of pathogenicity rs104894299 11:47469631-47469631 11:47448079-47448079
30 CHRNE NM_000080.4(CHRNE): c.905C> G (p.Pro302Arg) single nucleotide variant Conflicting interpretations of pathogenicity rs370019023 17:4804100-4804100 17:4900805-4900805
31 RYR1 NM_000540.2(RYR1): c.4115C> T (p.Ala1372Val) single nucleotide variant Uncertain significance rs370966353 19:38964366-38964366 19:38473726-38473726
32 RYR1 NM_000540.2(RYR1): c.4236C> G (p.His1412Gln) single nucleotide variant Uncertain significance rs146206507 19:38966033-38966033 19:38475393-38475393
33 CHRND NM_000751.3(CHRND): c.1181A> C (p.Lys394Thr) single nucleotide variant Uncertain significance rs1553575390 2:233398774-233398774 2:232534064-232534064
34 CHRNE NM_000080.4(CHRNE): c.1480T> C (p.Ter494Gln) single nucleotide variant Uncertain significance 17:4802033-4802033 17:4898738-4898738
35 CHRNE NM_000080.4(CHRNE): c.385_388del (p.Leu129fs) deletion Uncertain significance 17:4805338-4805342 17:4902045-4902048

Expression for Congenital Myasthenic Syndrome

Search GEO for disease gene expression data for Congenital Myasthenic Syndrome.

Pathways for Congenital Myasthenic Syndrome

Pathways related to Congenital Myasthenic Syndrome according to KEGG:

37
# Name Kegg Source Accession
1 Neuroactive ligand-receptor interaction hsa04080
2 Glycerophospholipid metabolism hsa00564
3 Cholinergic synapse hsa04725
4 ECM-receptor interaction hsa04512
5 Amino sugar and nucleotide sugar metabolism hsa00520

Pathways related to Congenital Myasthenic Syndrome according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.59 SLC5A7 CHRNE CHRND CHRNA1 CHAT ACHE
2
Show member pathways
11.96 GMPPB GFPT1 DPAGT1 ALG14
3
Show member pathways
11.49 CHRNE CHRND CHRNA1
4 11.01 RAPSN MUSK CHRNA1 AGRN
5 10.9 CHAT ACHE
6
Show member pathways
10.78 CHAT ACHE
7 10.41 SLC5A7 CHAT ACHE
8 10.17 CHAT ACHE
9 10 CHRNE CHRND CHRNB1 CHRNA1

GO Terms for Congenital Myasthenic Syndrome

Cellular components related to Congenital Myasthenic Syndrome according to GeneCards Suite gene sharing:

(show all 14)
# Name GO ID Score Top Affiliating Genes
1 cell junction GO:0030054 9.93 VAMP1 SLC5A7 RAPSN MUSK DOK7 COLQ
2 neuron projection GO:0043005 9.85 VAMP1 CHRNE CHRND CHRNB1 CHRNA1 CHAT
3 postsynaptic membrane GO:0045211 9.8 RAPSN MUSK CHRNE CHRND CHRNB1 CHRNA1
4 synapse GO:0045202 9.73 VAMP1 SLC5A7 RAPSN MUSK DOK7 COLQ
5 presynapse GO:0098793 9.71 VAMP1 SLC5A7 CHAT
6 basement membrane GO:0005604 9.67 COLQ AGRN ACHE
7 integral component of postsynaptic specialization membrane GO:0099060 9.58 CHRND CHRNB1 CHRNA1
8 acetylcholine-gated channel complex GO:0005892 9.56 CHRNE CHRND CHRNB1 CHRNA1
9 synaptic cleft GO:0043083 9.51 COLQ ACHE
10 neuromuscular junction GO:0031594 9.32 VAMP1 SLC5A7 RAPSN MUSK COLQ CHRNE
11 membrane GO:0016020 10.34 VAMP1 SLC5A7 SLC25A1 SCN4A RAPSN MYO9A
12 plasma membrane GO:0005886 10.3 SLC5A7 SCN4A RAPSN MUSK DOK7 COLQ
13 integral component of membrane GO:0016021 10.27 VAMP1 SLC5A7 SLC25A1 SCN4A MYO9A MUSK
14 integral component of plasma membrane GO:0005887 10.02 VAMP1 SCN4A MUSK CHRNE CHRND CHRNB1

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

(show all 25)
# Name GO ID Score Top Affiliating Genes
1 ion transmembrane transport GO:0034220 9.91 CHRNE CHRND CHRNB1 CHRNA1
2 chemical synaptic transmission GO:0007268 9.89 RAPSN CHRNE CHRND CHRNB1 CHRNA1
3 regulation of membrane potential GO:0042391 9.83 CHRNE CHRND CHRNB1 CHRNA1
4 muscle contraction GO:0006936 9.81 SCN4A CHRNE CHRND CHRNB1
5 cation transport GO:0006812 9.77 CHRND CHRNB1 CHRNA1
6 excitatory postsynaptic potential GO:0060079 9.73 CHRNE CHRND CHRNB1 CHRNA1
7 nervous system process GO:0050877 9.67 CHRNE CHRND CHRNB1 CHRNA1
8 skeletal muscle contraction GO:0003009 9.63 CHRND CHRNB1 CHRNA1
9 neuronal action potential GO:0019228 9.62 SCN4A CHRNA1
10 neuromuscular process GO:0050905 9.62 CHRND CHRNA1
11 regulation of postsynaptic membrane potential GO:0060078 9.62 CHRNE CHRND CHRNB1 CHRNA1
12 dolichol-linked oligosaccharide biosynthetic process GO:0006488 9.61 DPAGT1 ALG14
13 neurotransmitter catabolic process GO:0042135 9.59 COLQ ACHE
14 skeletal muscle acetylcholine-gated channel clustering GO:0071340 9.58 MUSK COLQ
15 UDP-N-acetylglucosamine metabolic process GO:0006047 9.58 GFPT1 DPAGT1
16 neurotransmitter biosynthetic process GO:0042136 9.58 SLC5A7 CHAT ACHE
17 musculoskeletal movement GO:0050881 9.56 CHRND CHRNA1
18 response to nicotine GO:0035094 9.56 CHRNE CHRND CHRNB1 CHRNA1
19 skeletal muscle tissue growth GO:0048630 9.55 CHRND CHRNA1
20 acetylcholine biosynthetic process GO:0008292 9.54 SLC5A7 CHAT
21 acetylcholine catabolic process in synaptic cleft GO:0001507 9.48 COLQ ACHE
22 neuromuscular synaptic transmission GO:0007274 9.43 SLC5A7 CHRNE CHRND CHRNB1 CHRNA1 CHAT
23 regulation of synaptic growth at neuromuscular junction GO:0008582 9.33 MUSK COLQ AGRN
24 synaptic transmission, cholinergic GO:0007271 9.1 SLC5A7 RAPSN CHRNE CHRND CHRNB1 CHRNA1
25 ion transport GO:0006811 10.04 SLC5A7 SCN4A CHRNE CHRND CHRNB1 CHRNA1

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

# Name GO ID Score Top Affiliating Genes
1 ion channel activity GO:0005216 9.8 SCN4A CHRNE CHRND CHRNB1 CHRNA1
2 extracellular ligand-gated ion channel activity GO:0005230 9.67 CHRNE CHRND CHRNB1 CHRNA1
3 transmembrane signaling receptor activity GO:0004888 9.61 CHRND CHRNB1 CHRNA1
4 transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential GO:1904315 9.56 CHRNE CHRND CHRNB1 CHRNA1
5 laminin binding GO:0043236 9.46 AGRN ACHE
6 acetylcholine-gated cation-selective channel activity GO:0022848 9.46 CHRNE CHRND CHRNB1 CHRNA1
7 ligand-gated ion channel activity GO:0015276 9.32 CHRND CHRNB1
8 acetylcholine receptor activity GO:0015464 9.26 CHRNE CHRND CHRNB1 CHRNA1
9 acetylcholine binding GO:0042166 9.02 CHRNE CHRND CHRNB1 CHRNA1 ACHE

Sources for Congenital Myasthenic Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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