CMS
MCID: CNG001
MIFTS: 66

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 52 25 58 36 29 6 15
Congenital Myasthenia 24 52 25 53
Congenital Myasthenic Syndromes 24 52 25
Cms 52 25 58
Myasthenic Syndromes, Congenital 43 71
Congenital Myasthenic Syndrome Ib 71
Syndrome, Myasthenic, Congenital 39
Myasthenic Syndromes Congenital 54
Myasthenia - Congenital 53

Characteristics:

Orphanet epidemiological data:

58
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:

Orphanet: 58  
Rare neurological diseases
Rare eye diseases
Developmental anomalies during embryogenesis


Summaries for Congenital Myasthenic Syndrome

NINDS : 53 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 postsynaptic congenital myasthenic syndromes and slow-channel congenital myasthenic syndrome, 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, testes and skeletal muscle, and related phenotypes are dysphagia and ptosis

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 : 52 Congenital myasthenic syndromes (CMS) are a group of genetic conditions that all include muscle weakness that gets worse with physical activity. There are many subtypes of CMS with different symptoms, severity, and treatments. Most people with CMS develop symptoms in infancy or by early childhood, but the age at which symptoms begin can vary. Symptoms range from mild to severe muscle weakness and may get worse over time or only occur periodically. The muscles of the face, neck, throat, eyes and limbs are most affected. There are at least 32 genes associated with CMS. Most are inherited in an autosomal recessive pattern. Genetic testing is necessary to tell the difference between subtypes. Treatment is based on managing the symptoms, and may differ depending on the subtype. The long-term outlook is not well understood and differs greatly from person to person.

KEGG : 36 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 : 74 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 839)
# Related Disease Score Top Affiliating Genes
1 postsynaptic congenital myasthenic syndromes 35.2 SCN4A RAPSN MUSK DOK7 CHRNE CHRND
2 slow-channel congenital myasthenic syndrome 35.1 CHRNE CHRND CHRNB1 CHRNA1
3 presynaptic congenital myasthenic syndromes 35.0 VAMP1 SLC5A7 SLC25A1 MYO9A CHAT AGRN
4 myasthenic syndrome, congenital, 4c, associated with acetylcholine receptor deficiency 35.0 VAMP1 RAPSN MUSK GFPT1 CHRNE
5 myasthenic syndrome, congenital, 13 34.9 RAPSN DPAGT1 DOK7 COLQ CHRNE CHRND
6 myasthenic syndrome, congenital, 5 34.9 RAPSN DOK7 COLQ ACHE
7 congenital myasthenic syndromes with glycosylation defect 34.9 GMPPB GFPT1 DPAGT1 ALG14
8 myasthenic syndrome, congenital, 21, presynaptic 34.8 RAPSN GFPT1 DPAGT1 DOK7 COLQ CHAT
9 congenital myasthenic syndrome with episodic apnea 34.8 SLC5A7 CHAT
10 myasthenic syndrome, congenital, 14 34.6 MYO9A CHRNB1 ALG14
11 myasthenic syndrome, congenital, 19 34.5 CHRNE CHRND CHRNB1
12 myasthenic syndrome, congenital, 1a, slow-channel 34.5 CHRND CHRNA1
13 muscular dystrophy-dystroglycanopathy , type c, 14 33.4 GMPPB ALG14
14 ptosis 32.8 SLC5A7 SCN4A RAPSN MUSK DOK7 COLQ
15 polyhydramnios 32.5 RAPSN MUSK DOK7
16 myasthenia gravis 32.3 RAPSN MUSK DOK7 CHRNE CHRNA1 AGRN
17 neuromuscular disease 32.0 SCN4A RAPSN MUSK GMPPB GFPT1 DPAGT1
18 peripheral nervous system disease 31.3 SCN4A RAPSN MUSK DOK7 COLQ CHRNE
19 muscular dystrophy, congenital, lmna-related 31.2 RAPSN GMPPB DOK7 COLQ CHRNE AGRN
20 neonatal myasthenia gravis 31.0 MUSK COLQ AGRN
21 myopathy, tubular aggregate, 1 31.0 GFPT1 DOK7 COLQ
22 cenani-lenz syndactyly syndrome 30.9 RAPSN MUSK DOK7 AGRN
23 sclerosteosis 2 30.6 RAPSN DOK7
24 myasthenic syndrome, congenital, 6, presynaptic 12.4
25 myasthenic syndrome, congenital, 10 12.3
26 myasthenic syndrome, congenital, 16 12.3
27 myasthenic syndrome, congenital, 1b, fast-channel 12.3
28 myasthenic syndrome, congenital, 4a, slow-channel 12.3
29 myasthenic syndrome, congenital, 8 12.3
30 myasthenic syndrome, congenital, 11, associated with acetylcholine receptor deficiency 12.3
31 myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency 12.2
32 myasthenic syndrome, congenital, 3b, fast-channel 12.2
33 myasthenic syndrome, congenital, 7, presynaptic 12.2
34 myasthenic syndrome, congenital, 2c, associated with acetylcholine receptor deficiency 12.2
35 myasthenic syndrome, congenital, 3a, slow-channel 12.2
36 capillary malformation-arteriovenous malformation 1 12.2
37 myasthenic syndrome, congenital, 12 12.2
38 congenital myasthenic syndrome associated with acetylcholine receptor deficiency 12.2
39 myasthenic syndrome, congenital, 4b, fast-channel 12.2
40 myasthenic syndrome, congenital, 3c, associated with acetylcholine receptor deficiency 12.2
41 myasthenic syndrome, congenital, 15 12.2
42 myasthenic syndrome, congenital, 20, presynaptic 12.2
43 myasthenic syndrome, congenital, 22 12.2
44 myasthenic syndrome, congenital, 17 12.1
45 myasthenic syndrome, congenital, 18 12.1
46 megalencephaly-capillary malformation-polymicrogyria syndrome 11.9
47 myasthenic syndrome, congenital, 2a, slow-channel 11.7
48 chronic mountain sickness 11.7
49 myasthenic syndrome, congenital, 25, presynaptic 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:

58 31 (show top 50) (show all 69)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 dysphagia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002015
2 ptosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0000508
3 poor suck 58 31 hallmark (90%) Very frequent (99-80%) HP:0002033
4 proximal muscle weakness 58 31 hallmark (90%) Very frequent (99-80%) HP:0003701
5 fatigable weakness 58 31 hallmark (90%) Very frequent (99-80%) HP:0003473
6 neck muscle weakness 58 31 hallmark (90%) Very frequent (99-80%) HP:0000467
7 sudden episodic apnea 58 31 hallmark (90%) Very frequent (99-80%) HP:0002882
8 intermittent episodes of respiratory insufficiency due to muscle weakness 58 31 hallmark (90%) Very frequent (99-80%) HP:0004889
9 frontalis muscle weakness 58 31 hallmark (90%) Very frequent (99-80%) HP:0004661
10 intellectual disability 58 31 frequent (33%) Frequent (79-30%) HP:0001249
11 recurrent respiratory infections 58 31 frequent (33%) Frequent (79-30%) HP:0002205
12 generalized muscle weakness 58 31 frequent (33%) Frequent (79-30%) HP:0003324
13 ataxia 58 31 frequent (33%) Frequent (79-30%) HP:0001251
14 easy fatigability 58 31 frequent (33%) Frequent (79-30%) HP:0003388
15 ophthalmoplegia 58 31 frequent (33%) Frequent (79-30%) HP:0000602
16 nasal speech 58 31 frequent (33%) Frequent (79-30%) HP:0001611
17 decreased fetal movement 58 31 frequent (33%) Frequent (79-30%) HP:0001558
18 arthrogryposis multiplex congenita 58 31 frequent (33%) Frequent (79-30%) HP:0002804
19 cyanosis 58 31 frequent (33%) Frequent (79-30%) HP:0000961
20 difficulty walking 58 31 frequent (33%) Frequent (79-30%) HP:0002355
21 choking episodes 58 31 frequent (33%) Frequent (79-30%) HP:0030842
22 central sleep apnea 58 31 frequent (33%) Frequent (79-30%) HP:0010536
23 bulbar palsy 58 31 frequent (33%) Frequent (79-30%) HP:0001283
24 muscle fiber atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0100295
25 emg: impaired neuromuscular transmission 58 31 frequent (33%) Frequent (79-30%) HP:0100285
26 spinal deformities 58 31 frequent (33%) Frequent (79-30%) HP:0008443
27 apneic episodes precipitated by illness, fatigue, stress 58 31 frequent (33%) Frequent (79-30%) HP:0002872
28 episodic respiratory distress 58 31 frequent (33%) Frequent (79-30%) HP:0004885
29 nasal regurgitation 58 31 frequent (33%) Frequent (79-30%) HP:0011469
30 high palate 58 31 occasional (7.5%) Occasional (29-5%) HP:0000218
31 waddling gait 58 31 occasional (7.5%) Occasional (29-5%) HP:0002515
32 spinal rigidity 58 31 occasional (7.5%) Occasional (29-5%) HP:0003306
33 emg: myopathic abnormalities 58 31 occasional (7.5%) Occasional (29-5%) HP:0003458
34 toe walking 58 31 occasional (7.5%) Occasional (29-5%) HP:0040083
35 motor delay 58 31 occasional (7.5%) Occasional (29-5%) HP:0001270
36 kyphoscoliosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002751
37 long face 58 31 occasional (7.5%) Occasional (29-5%) HP:0000276
38 areflexia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001284
39 dysphonia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001618
40 pes cavus 58 31 occasional (7.5%) Occasional (29-5%) HP:0001761
41 distal lower limb muscle weakness 58 31 occasional (7.5%) Occasional (29-5%) HP:0009053
42 distal amyotrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0003693
43 poor head control 58 31 occasional (7.5%) Occasional (29-5%) HP:0002421
44 weak cry 58 31 occasional (7.5%) Occasional (29-5%) HP:0001612
45 stridor 58 31 occasional (7.5%) Occasional (29-5%) HP:0010307
46 central hypotonia 58 31 occasional (7.5%) Occasional (29-5%) HP:0011398
47 limb-girdle muscle weakness 58 31 occasional (7.5%) Occasional (29-5%) HP:0003325
48 narrow jaw 58 31 occasional (7.5%) Occasional (29-5%) HP:0012801
49 seizure 31 occasional (7.5%) HP:0001250
50 pectus carinatum 58 31 very rare (1%) Very rare (<4-1%) HP:0000768

UMLS symptoms related to Congenital Myasthenic Syndrome:


facial paresis

MGI Mouse Phenotypes related to Congenital Myasthenic Syndrome:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.1 ACHE AGRN CHAT CHRNA1 CHRNE DOK7
2 mortality/aging MP:0010768 10.1 ACHE AGRN ALG14 CHAT CHRNA1 CHRNE
3 muscle MP:0005369 9.81 ACHE AGRN CHAT CHRNE DOK7 GFPT1
4 nervous system MP:0003631 9.73 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 16)
# 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 Adrenergic Agents Phase 1, Phase 2
5 Vasoconstrictor Agents Phase 1, Phase 2
6 Central Nervous System Stimulants Phase 1, Phase 2
7 Sympathomimetics Phase 1, Phase 2
8 Adrenergic beta-Agonists Phase 1
9 Respiratory System Agents Phase 1
10 Anti-Asthmatic Agents Phase 1
11 Albuterol Phase 1
12 Adrenergic Agonists Phase 1
13 Tocolytic Agents Phase 1
14 Bronchodilator Agents Phase 1
15
Amifampridine Approved, Investigational 54-96-6 5918
16 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) Completed 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 Congenital Muscle Disease Patient and Proxy Reported Outcome Study Unknown status NCT01403402
5 Retrospective Study :Describe the Changes of the Disease in Many Cases Likely to Aggravate. Completed NCT01474980
6 National Registry for Egyptian Pediatric Neuromuscular Diseases Recruiting NCT02124616
7 Open Label Trial Of 3,4-Diaminopyridine In Lambert-Eaton Myasthenic Syndrome (LEMS) and Congenital Myasthenic Syndromes (CMS) Active, not recruiting NCT00872950 3,4-DIAMINOPYRIDINE
8 Treatment Use of 3,4 Diaminopyridine in Congenital Myasthenia and Lambert-Eaton Syndrome Available NCT03062631 3,4-Diaminopyridine
9 An Open-Label, Expanded Access Protocol for Amifampridine Phosphate Treatment in Patients With Congenital Myasthenic Syndrome (CMS) No longer available NCT02189720 Amifampridine Phosphate
10 Treatment Use of 3,4-Diaminopyridine in Congenital Myasthenic Syndrome No longer available NCT01765140 3,4-diaminopyridine
11 3,4-Diaminopyridine for Lambert-Eaton Myasthenic Syndrome and Congenital Myasthenia No longer available NCT02012933 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:

40
Eye, Testes, Skeletal Muscle, Skin, Brain, Bone, Thymus

Publications for Congenital Myasthenic Syndrome

Articles related to Congenital Myasthenic Syndrome:

(show top 50) (show all 654)
# Title Authors PMID Year
1
Mutations in MUSK causing congenital myasthenic syndrome impair MuSK-Dok-7 interaction. 61 54 24 6
20371544 2010
2
CHRND mutation causes a congenital myasthenic syndrome by impairing co-clustering of the acetylcholine receptor with rapsyn. 6 24 61 54
16916845 2006
3
Congenital myasthenic syndromes. 24 6 54 61
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). 24 6 54 61
9758617 1998
5
Human endplate acetylcholinesterase deficiency caused by mutations in the collagen-like tail subunit (ColQ) of the asymmetric enzyme. 61 54 6 24
9689136 1998
6
Congenital Myasthenic Syndrome Type 19 Is Caused by Mutations in COL13A1, Encoding the Atypical Non-fibrillar Collagen Type XIII α1 Chain. 6 24 61
26626625 2015
7
LRP4 third β-propeller domain mutations cause novel congenital myasthenia by compromising agrin-mediated MuSK signaling in a position-specific manner. 6 61 24
24234652 2014
8
Clinical and pathological heterogeneity of a congenital disorder of glycosylation manifesting as a myasthenic/myopathic syndrome. 61 24 6
24461433 2014
9
Congenital myasthenic syndromes due to mutations in ALG2 and ALG14. 6 61 24
23404334 2013
10
LG2 agrin mutation causing severe congenital myasthenic syndrome mimics functional characteristics of non-neural (z-) agrin. 61 24 6
22205389 2012
11
Mutations in DPAGT1 cause a limb-girdle congenital myasthenic syndrome with tubular aggregates. 6 24 61
22742743 2012
12
Identification of an agrin mutation that causes congenital myasthenia and affects synapse function. 24 6 61
19631309 2009
13
Mutation analysis of CHRNA1, CHRNB1, CHRND, and RAPSN genes in multiple pterygium syndrome/fetal akinesia patients. 24 6 61
18179903 2008
14
MUSK, a new target for mutations causing congenital myasthenic syndrome. 61 6 24
15496425 2004
15
Mutation history of the roma/gypsies. 6 24 61
15322984 2004
16
The congenital myasthenic syndrome mutation RAPSN N88K derives from an ancient Indo-European founder. 61 6 24
15286164 2004
17
E-box mutations in the RAPSN promoter region in eight cases with congenital myasthenic syndrome. 6 61 24
12651869 2003
18
Choline acetyltransferase mutations cause myasthenic syndrome associated with episodic apnea in humans. 6 24 61
11172068 2001
19
Mutation causing congenital myasthenia reveals acetylcholine receptor beta/delta subunit interaction essential for assembly. 6 24 61
10562302 1999
20
A common mutation (epsilon1267delG) in congenital myasthenic patients of Gypsy ethnic origin. 61 24 6
10534268 1999
21
Mutation of the acetylcholine receptor epsilon-subunit promoter in congenital myasthenic syndrome. 6 61 24
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. 61 24 6
9158151 1997
23
Mutant SNAP25B causes myasthenia, cortical hyperexcitability, ataxia, and intellectual disability. 24 6
25381298 2014
24
Synaptotagmin 2 mutations cause an autosomal-dominant form of lambert-eaton myasthenic syndrome and nonprogressive motor neuropathy. 6 24
25192047 2014
25
Hexosamine biosynthetic pathway mutations cause neuromuscular transmission defect. 6 24
21310273 2011
26
Refinement of the clinical phenotype in musk-related congenital myasthenic syndromes. 6 24
19949040 2009
27
Congenital myasthenic syndrome caused by two non-N88K rapsyn mutations. 61 54 6
17594401 2007
28
Impaired receptor clustering in congenital myasthenic syndrome with novel RAPSN mutations. 6 61 54
16931511 2006
29
Dok-7 mutations underlie a neuromuscular junction synaptopathy. 6 24
16917026 2006
30
Regulation of the rapsyn promoter by kaiso and delta-catenin. 6 54 61
15282317 2004
31
Rapsyn mutations in hereditary myasthenia: distinct early- and late-onset phenotypes. 6 24
14504330 2003
32
Myasthenic syndrome caused by mutation of the SCN4A sodium channel. 6 24
12766226 2003
33
Congenital myasthenic syndrome with episodic apnea in patients homozygous for a CHAT missense mutation. 6 54 61
12756141 2003
34
Identification of pathogenic mutations in the human rapsyn gene. 54 61 6
12730725 2003
35
Recessive inheritance and variable penetrance of slow-channel congenital myasthenic syndromes. 6 24
12141316 2002
36
Rapsyn mutations in humans cause endplate acetylcholine-receptor deficiency and myasthenic syndrome. 24 6
11791205 2002
37
Acetylcholine receptor delta subunit mutations underlie a fast-channel myasthenic syndrome and arthrogryposis multiplex congenita. 6 24
11435464 2001
38
Immature end-plates and utrophin deficiency in congenital myasthenic syndrome caused by epsilon-AChR subunit truncating mutations. 54 61 6
11030414 2000
39
Biallelic c.1263dupC in DOK7 results in fetal akinesia deformation sequence. 6 61
31880392 2020
40
Leukoencephalopathy due to variants in GFPT1-associated congenital myasthenic syndrome. 61 6
30635494 2019
41
Defective fast inactivation recovery of Nav 1.4 in congenital myasthenic syndrome. 61 6
25707578 2015
42
Use of next-generation sequencing as a diagnostic tool for congenital myasthenic syndrome. 6 61
25194721 2014
43
Highly fatal fast-channel syndrome caused by AChR ε subunit mutation at the agonist binding site. 61 6
22592360 2012
44
Germline mutation in DOK7 associated with fetal akinesia deformation sequence. 6 61
19261599 2009
45
The CHRNE 1293insG founder mutation is a frequent cause of congenital myasthenia in North Africa. 61 6
19064877 2008
46
hnRNP H enhances skipping of a nonfunctional exon P3A in CHRNA1 and a mutation disrupting its binding causes congenital myasthenic syndrome. 6 61
18806275 2008
47
Congenital myasthenia-related AChR delta subunit mutation interferes with intersubunit communication essential for channel gating. 6 61
18398509 2008
48
Clinical features of the DOK7 neuromuscular junction synaptopathy. 24 61 54
17452375 2007
49
An intronic base alteration of the CHRNE gene leading to a congenital myasthenic syndrome. 6 61
16087917 2005
50
Congenital endplate acetylcholinesterase deficiency responsive to ephedrine. 54 61 24
16009904 2005

Variations for Congenital Myasthenic Syndrome

ClinVar genetic disease variations for Congenital Myasthenic Syndrome:

6 (show top 50) (show all 257) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 CHRNE NM_000080.4(CHRNE):c.1090dup (p.Arg364fs)duplication Pathogenic 434765 rs1156634884 17:4802621-4802622 17:4899326-4899327
2 GFPT1 NM_001244710.1(GFPT1):c.686-2A>GSNV Pathogenic 540353 rs1011196447 2:69581446-69581446 2:69354314-69354314
3 VAMP1 NM_014231.5(VAMP1):c.146G>C (p.Arg49Pro)SNV Pathogenic 549692 rs754046104 12:6575150-6575150 12:6465984-6465984
4 CHRNE NM_000080.4(CHRNE):c.442T>A (p.Cys148Ser)SNV Pathogenic 694659 17:4805285-4805285 17:4901990-4901990
5 DOK7 NM_173660.5(DOK7):c.1124_1127dup (p.Ala378fs)duplication Pathogenic 1273 rs606231128 4:3494833-3494834 4:3493106-3493107
6 SCN4A NM_000334.4(SCN4A):c.4325T>A (p.Val1442Glu)SNV Pathogenic 5914 rs121908553 17:62019317-62019317 17:63941957-63941957
7 COLQ NM_005677.4(COLQ):c.1082del (p.Pro361fs)deletion Pathogenic 6652 rs769982050 3:15497519-15497519 3:15456012-15456012
8 RAPSN NM_005055.4(RAPSN):c.-210A>GSNV Pathogenic 8051 rs786200905 11:47470726-47470726 11:47449174-47449174
9 CHAT NM_020549.4(CHAT):c.914T>C (p.Ile305Thr)SNV Pathogenic 17513 rs75466054 10:50833680-50833680 10:49625634-49625634
10 AGRN NM_198576.4(AGRN):c.5125G>C (p.Gly1709Arg)SNV Pathogenic 18241 rs199476396 1:985955-985955 1:1050575-1050575
11 AGRN NM_198576.4(AGRN):c.5179G>T (p.Val1727Phe)SNV Pathogenic 126555 rs587777298 1:986143-986143 1:1050763-1050763
12 AGRN NM_198576.4(AGRN):c.1057C>T (p.Gln353Ter)SNV Pathogenic 126556 rs587777299 1:976962-976962 1:1041582-1041582
13 AGRN NM_198576.4(AGRN):c.226G>A (p.Gly76Ser)SNV Pathogenic 243036 rs756623659 1:957605-957605 1:1022225-1022225
14 AGRN NM_198576.4(AGRN):c.314A>T (p.Asn105Ile)SNV Pathogenic 243037 rs879253787 1:957693-957693 1:1022313-1022313
15 AGRN NM_198576.4(AGRN):c.1362dup (p.Ser455fs)duplication Pathogenic 243038 rs879253788 1:977516-977517 1:1042136-1042137
16 AGRN NM_198576.4(AGRN):c.5023G>A (p.Gly1675Ser)SNV Pathogenic 243039 rs764160563 1:985853-985853 1:1050473-1050473
17 CHRNE NM_000080.4(CHRNE):c.1353dup (p.Asn452fs)duplication Pathogenic 243032 rs773526895 17:4802159-4802160 17:4898864-4898865
18 CHRNE NM_000080.4(CHRNE):c.1327delGdeletion Pathogenic 243031 rs763258280 17:4802186-4802186 17:4898891-4898891
19 CHRNE NM_000080.4(CHRNE):c.130dup (p.Glu44fs)duplication Pathogenic 243030 rs762368691 17:4805974-4805975 17:4902679-4902680
20 CHRNE NC_000017.11:g.4902680_4903969del1290insTCTGGATGCGindel Pathogenic 243033 17:4805975-4807264 17:4902680-4903969
21 AGRN 1p36.33 deletion (0.48 Mb)deletion Pathogenic 243041
22 RAPSN NM_005055.4(RAPSN):c.-199C>GSNV Pathogenic 264677 rs886037842 11:47470715-47470715 11:47449163-47449163
23 GMPPB NM_021971.4(GMPPB):c.1000G>A (p.Asp334Asn)SNV Pathogenic/Likely pathogenic 60540 rs397509422 3:49759268-49759268 3:49721835-49721835
24 CHRNE NM_000080.4(CHRNE):c.183_187dup (p.Leu63fs)duplication Pathogenic/Likely pathogenic 429303 rs776927709 17:4805917-4805918 17:4902622-4902623
25 COLQ NM_005677.4(COLQ):c.279C>A (p.Cys93Ter)SNV Likely pathogenic 636303 3:15529755-15529755 3:15488248-15488248
26 AGRN NM_198576.4(AGRN):c.569_573CGGGC[3] (p.Ser194fs)short repeat Likely pathogenic 666960 1:976097-976098 1:1040717-1040718
27 CHRNA1 NM_000079.4(CHRNA1):c.380_381del (p.Lys127fs)deletion Likely pathogenic 667020 2:175619106-175619107 2:174754378-174754379
28 CHRNE NM_000080.4(CHRNE):c.1252_1267dup (p.Cys423fs)duplication Likely pathogenic 694644 17:4802354-4802355 17:4899059-4899060
29 CHRNE NM_000080.4(CHRNE):c.488C>T (p.Ser163Leu)SNV Conflicting interpretations of pathogenicity 18360 rs121909516 17:4805239-4805239 17:4901944-4901944
30 SCN4A NM_000334.4(SCN4A):c.737C>T (p.Ser246Leu)SNV Conflicting interpretations of pathogenicity 21161 rs80338951 17:62045682-62045682 17:63968322-63968322
31 CHRNE NM_000080.4(CHRNE):c.710G>T (p.Arg237Leu)SNV Conflicting interpretations of pathogenicity 40228 rs201434993 17:4804377-4804377 17:4901082-4901082
32 RAPSN NM_005055.5(RAPSN):c.264C>A (p.Asn88Lys)SNV Conflicting interpretations of pathogenicity 8046 rs104894299 11:47469631-47469631 11:47448079-47448079
33 CHRND NM_000751.3(CHRND):c.*908A>GSNV Conflicting interpretations of pathogenicity 896197 2:233400930-233400930 2:232536220-232536220
34 CHAT NM_020549.4(CHAT):c.406G>A (p.Val136Met)SNV Conflicting interpretations of pathogenicity 279754 rs201479289 10:50827789-50827789 10:49619743-49619743
35 CHRND NM_000751.3(CHRND):c.919C>T (p.Pro307Ser)SNV Conflicting interpretations of pathogenicity 281423 rs142063328 2:233396160-233396160 2:232531450-232531450
36 CHRNE NM_000080.4(CHRNE):c.103T>C (p.Tyr35His)SNV Conflicting interpretations of pathogenicity 282036 rs144169073 17:4806002-4806002 17:4902707-4902707
37 CHRNE NM_000080.4(CHRNE):c.*5C>TSNV Conflicting interpretations of pathogenicity 254886 rs747566295 17:4802026-4802026 17:4898731-4898731
38 CHRNE NM_000080.4(CHRNE):c.1416C>T (p.Leu472=)SNV Conflicting interpretations of pathogenicity 254892 rs145456588 17:4802097-4802097 17:4898802-4898802
39 CHRND NM_000751.3(CHRND):c.1530C>T (p.Asn510=)SNV Conflicting interpretations of pathogenicity 288058 rs114463490 2:233399998-233399998 2:232535288-232535288
40 CHRNA1 NM_001039523.3(CHRNA1):c.1368C>T (p.Leu456=)SNV Conflicting interpretations of pathogenicity 332437 rs146899588 2:175612933-175612933 2:174748205-174748205
41 CHRNE NM_000080.4(CHRNE):c.465C>T (p.Phe155=)SNV Conflicting interpretations of pathogenicity 254898 rs139625105 17:4805262-4805262 17:4901967-4901967
42 CHRNE NM_000080.4(CHRNE):c.6A>G (p.Ala2=)SNV Conflicting interpretations of pathogenicity 254901 rs202198207 17:4806353-4806353 17:4903058-4903058
43 CHRNA1 NM_001039523.3(CHRNA1):c.*422G>TSNV Conflicting interpretations of pathogenicity 332429 rs184095877 2:175612430-175612430 2:174747702-174747702
44 CHRND NM_000751.3(CHRND):c.198+14C>TSNV Conflicting interpretations of pathogenicity 256780 rs199538903 2:233391398-233391398 2:232526688-232526688
45 CHRND NM_000751.3(CHRND):c.1400G>A (p.Arg467His)SNV Conflicting interpretations of pathogenicity 194006 rs148939701 2:233399868-233399868 2:232535158-232535158
46 CHRNA1 NM_001039523.3(CHRNA1):c.730C>T (p.Leu244=)SNV Conflicting interpretations of pathogenicity 198039 rs150638770 2:175618354-175618354 2:174753626-174753626
47 CHRND NM_000751.3(CHRND):c.862C>G (p.Gln288Glu)SNV Conflicting interpretations of pathogenicity 198749 rs41265127 2:233396103-233396103 2:232531393-232531393
48 CHRNE NM_000080.4(CHRNE):c.1220-2A>GSNV Conflicting interpretations of pathogenicity 631777 rs1309292778 17:4802404-4802404 17:4899109-4899109
49 CHRNE NM_000080.4(CHRNE):c.1104C>T (p.Pro368=)SNV Conflicting interpretations of pathogenicity 706191 17:4802608-4802608 17:4899313-4899313
50 CHRNE NM_000080.4(CHRNE):c.23T>C (p.Val8Ala)SNV Conflicting interpretations of pathogenicity 705677 17:4806336-4806336 17:4903041-4903041

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:

36
# 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
11.91 GMPPB GFPT1 DPAGT1 ALG14
3
Show member pathways
11.49 CHRNE CHRND CHRNA1
4 11.01 RAPSN MUSK CHRNA1 AGRN
5
Show member pathways
10.78 CHAT ACHE
6 10.41 SLC5A7 CHAT ACHE
7 10.21 CHAT ACHE
8 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 13)
# Name GO ID Score Top Affiliating Genes
1 membrane GO:0016020 10.38 VAMP1 SLC5A7 SLC25A1 SCN4A RAPSN MYO9A
2 integral component of membrane GO:0016021 10.28 VAMP1 SLC5A7 SLC25A1 SCN4A MYO9A MUSK
3 plasma membrane GO:0005886 10.27 VAMP1 SLC5A7 SCN4A RAPSN MUSK DOK7
4 integral component of plasma membrane GO:0005887 10.04 VAMP1 SCN4A MUSK CHRNE CHRND CHRNB1
5 cell junction GO:0030054 9.97 VAMP1 SLC5A7 RAPSN MYO9A MUSK DOK7
6 neuron projection GO:0043005 9.88 VAMP1 CHRNE CHRND CHRNB1 CHRNA1 CHAT
7 postsynaptic membrane GO:0045211 9.85 RAPSN MUSK CHRNE CHRND CHRNB1 CHRNA1
8 basement membrane GO:0005604 9.69 COLQ AGRN ACHE
9 neuromuscular junction GO:0031594 9.65 VAMP1 SLC5A7 RAPSN MUSK COLQ CHRNE
10 integral component of postsynaptic specialization membrane GO:0099060 9.62 CHRNE CHRND CHRNB1 CHRNA1
11 acetylcholine-gated channel complex GO:0005892 9.56 CHRNE CHRND CHRNB1 CHRNA1
12 synaptic cleft GO:0043083 9.52 COLQ ACHE
13 synapse GO:0045202 9.47 VAMP1 SLC5A7 RAPSN MYO9A MUSK DOK7

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

(show all 24)
# Name GO ID Score Top Affiliating Genes
1 ion transport GO:0006811 10.05 SLC5A7 SCN4A CHRNE CHRND CHRNB1 CHRNA1
2 ion transmembrane transport GO:0034220 9.92 CHRNE CHRND CHRNB1 CHRNA1
3 chemical synaptic transmission GO:0007268 9.91 RAPSN CHRNE CHRND CHRNB1 CHRNA1
4 regulation of membrane potential GO:0042391 9.84 CHRNE CHRND CHRNB1 CHRNA1
5 muscle contraction GO:0006936 9.83 SCN4A CHRNE CHRND CHRNB1
6 cation transport GO:0006812 9.78 CHRND CHRNB1 CHRNA1
7 excitatory postsynaptic potential GO:0060079 9.76 CHRNE CHRND CHRNB1 CHRNA1
8 regulation of postsynaptic membrane potential GO:0060078 9.71 CHRNE CHRND CHRNB1 CHRNA1
9 skeletal muscle contraction GO:0003009 9.67 CHRND CHRNB1 CHRNA1
10 nervous system process GO:0050877 9.67 CHRNE CHRND CHRNB1 CHRNA1
11 response to nicotine GO:0035094 9.62 CHRNE CHRND CHRNB1 CHRNA1
12 dolichol-linked oligosaccharide biosynthetic process GO:0006488 9.61 DPAGT1 ALG14
13 neurotransmitter biosynthetic process GO:0042136 9.61 SLC5A7 CHAT ACHE
14 neurotransmitter catabolic process GO:0042135 9.6 COLQ ACHE
15 skeletal muscle acetylcholine-gated channel clustering GO:0071340 9.59 MUSK COLQ
16 UDP-N-acetylglucosamine metabolic process GO:0006047 9.58 GFPT1 DPAGT1
17 musculoskeletal movement GO:0050881 9.57 CHRND CHRNA1
18 skeletal muscle tissue growth GO:0048630 9.56 CHRND CHRNA1
19 neuromuscular junction development GO:0007528 9.56 MUSK DOK7 CHRNA1 AGRN
20 acetylcholine biosynthetic process GO:0008292 9.55 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

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 9.77 SCN4A CHRNE CHRND CHRNB1 CHRNA1
2 transmembrane signaling receptor activity GO:0004888 9.73 CHRNE CHRND CHRNB1 CHRNA1
3 neurotransmitter receptor activity GO:0030594 9.71 CHRNE CHRND CHRNB1 CHRNA1
4 extracellular ligand-gated ion channel activity GO:0005230 9.62 CHRNE CHRND CHRNB1 CHRNA1
5 transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential GO:1904315 9.56 CHRNE CHRND CHRNB1 CHRNA1
6 laminin binding GO:0043236 9.46 AGRN ACHE
7 acetylcholine-gated cation-selective channel activity GO:0022848 9.46 CHRNE CHRND CHRNB1 CHRNA1
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 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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