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CMS
MCID: CNG001
MIFTS: 68

Congenital Myasthenic Syndrome (CMS)

Categories: Eye diseases, Fetal diseases, Genetic diseases, Muscle diseases, Neuronal diseases, Rare diseases, Respiratory diseases
Genes Variations Tissues Related diseases Publications Pathways Symptoms & Phenotypes Drugs
Sources

Aliases & Classifications for Congenital Myasthenic Syndrome

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MalaCards integrated aliases for Congenital Myasthenic Syndrome:

Name: Congenital Myasthenic Syndrome 12 20 43 58 36 29 6 15
Congenital Myasthenia 25 20 43 53
Congenital Myasthenic Syndromes 25 20 43
Cms 20 43 58
Myasthenic Syndromes, Congenital 44 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:

25
Penetrance In general, reported cms pathogenic variants have complete penetrance....

Classifications:

MalaCards categories:
Global: Rare diseases Fetal diseases Genetic diseases
Anatomical: Neuronal diseases Eye diseases Respiratory diseases Muscle diseases
See all MalaCards categories (disease lists)
ICD10: 33
Orphanet: 58  
Rare neurological diseases
Rare eye diseases
Developmental anomalies during embryogenesis


Sources

Summaries for Congenital Myasthenic Syndrome

About this section
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 myasthenic syndrome, congenital, 13 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).

MedlinePlus Genetics : 43 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).

GARD : 20 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
Sources

Related Diseases for Congenital Myasthenic Syndrome

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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 257)
# Related Disease Score Top Affiliating Genes
1 myasthenic syndrome, congenital, 13 33.9 RAPSN DPAGT1 DOK7 COLQ CHRNE CHRND
2 myasthenic syndrome, congenital, 4c, associated with acetylcholine receptor deficiency 33.9 RAPSN MUSK GFPT1 CHRNE CHAT
3 myasthenic syndrome, congenital, 1a, slow-channel 33.7 CHRND CHRNB1 CHRNA1
4 myasthenic syndrome, congenital, 21, presynaptic 33.7 RAPSN GFPT1 DPAGT1 DOK7 COLQ CHAT
5 myasthenic syndrome, congenital, 5 33.7 RAPSN DOK7 COLQ
6 myasthenic syndrome, congenital, 19 33.6 SNAP25 RAPSN MUSK DOK7 COL13A1 CHAT
7 myasthenic syndrome, congenital, 1b, fast-channel 33.5 CHRNE CHRND CHRNA1
8 myasthenic syndrome, congenital, 14 33.5 CHRND CHRNB1 ALG2 ALG14
9 myasthenic syndrome, congenital, 16 33.4 SCN4A GH-LCR
10 slow-channel congenital myasthenic syndrome 33.2 CHRNE CHRND CHRNB1 CHRNA1
11 congenital myasthenic syndrome associated with acetylcholine receptor deficiency 32.9 RAPSN MUSK CHRNE CHAT
12 presynaptic congenital myasthenic syndromes 32.9 SNAP25 COL13A1 CHAT AGRN
13 ptosis 32.6 SNAP25 SCN4A RAPSN MUSK LRP4 DOK7
14 muscular dystrophy-dystroglycanopathy , type c, 14 32.5 GMPPB ALG14
15 myasthenia gravis 31.8 RAPSN MUSK LRP4 CHRNE CHRNA1 AGRN
16 neuromuscular disease 31.5 SCN4A RAPSN MUSK LRP4 GMPPB GFPT1
17 postsynaptic congenital myasthenic syndromes 31.5 SCN4A RAPSN MUSK LRP4 DOK7 COL13A1
18 congenital myasthenic syndromes with glycosylation defect 31.3 GMPPB GFPT1 DPAGT1 ALG2 ALG14
19 peripheral nervous system disease 31.1 SCN4A RAPSN MUSK DOK7 COLQ CHRNE
20 neonatal myasthenia gravis 31.0 MUSK LRP4 COLQ AGRN
21 paramyotonia congenita of von eulenburg 31.0 SCN4A GH-LCR CHRNE CHRND CHRNB1
22 muscular dystrophy, congenital, lmna-related 30.9 GMPPB DOK7 COLQ AGRN
23 congenital disorder of glycosylation, type in 30.9 DPAGT1 ALG2 ALG14
24 fetal akinesia deformation sequence 1 30.9 SCN4A RAPSN MUSK DOK7 CHRND CHRNB1
25 hyperkalemic periodic paralysis 30.8 SCN4A RAPSN GH-LCR
26 cenani-lenz syndactyly syndrome 30.8 RAPSN MUSK LRP4 DOK7 AGRN
27 sclerosteosis 2 30.6 RAPSN LRP4 DOK7
28 myotonia 30.6 SCN4A GH-LCR
29 myasthenic syndrome, congenital, 6, presynaptic 11.7
30 myasthenic syndrome, congenital, 10 11.7
31 myasthenic syndrome, congenital, 4a, slow-channel 11.7
32 myasthenic syndrome, congenital, 11, associated with acetylcholine receptor deficiency 11.7
33 myasthenic syndrome, congenital, 12 11.7
34 myasthenic syndrome, congenital, 3b, fast-channel 11.7
35 myasthenic syndrome, congenital, 8 11.6
36 myasthenic syndrome, congenital, 9, associated with acetylcholine receptor deficiency 11.6
37 myasthenic syndrome, congenital, 20, presynaptic 11.6
38 myasthenic syndrome, congenital, 15 11.6
39 myasthenic syndrome, congenital, 3a, slow-channel 11.6
40 myasthenic syndrome, congenital, 4b, fast-channel 11.6
41 myasthenic syndrome, congenital, 3c, associated with acetylcholine receptor deficiency 11.6
42 myasthenic syndrome, congenital, 7, presynaptic 11.6
43 myasthenic syndrome, congenital, 2c, associated with acetylcholine receptor deficiency 11.6
44 myasthenic syndrome, congenital, 18 11.6
45 myasthenic syndrome, congenital, 22 11.5
46 myasthenic syndrome, congenital, 17 11.5
47 congenital myasthenic syndrome with episodic apnea 11.5
48 chronic mountain sickness 11.3
49 myasthenic syndrome, congenital, 25, presynaptic 11.2
50 myasthenic syndrome, congenital, 2a, slow-channel 11.2

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



Diseases related to Congenital Myasthenic Syndrome
Sources

Symptoms & Phenotypes for Congenital Myasthenic Syndrome

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Human phenotypes related to Congenital Myasthenic Syndrome:

58 31 (show top 50) (show all 70)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ptosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0000508
2 dysphagia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002015
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 ataxia 58 31 frequent (33%) Frequent (79-30%) HP:0001251
12 recurrent respiratory infections 58 31 frequent (33%) Frequent (79-30%) HP:0002205
13 easy fatigability 58 31 frequent (33%) Frequent (79-30%) HP:0003388
14 ophthalmoplegia 58 31 frequent (33%) Frequent (79-30%) HP:0000602
15 nasal speech 58 31 frequent (33%) Frequent (79-30%) HP:0001611
16 decreased fetal movement 58 31 frequent (33%) Frequent (79-30%) HP:0001558
17 arthrogryposis multiplex congenita 58 31 frequent (33%) Frequent (79-30%) HP:0002804
18 generalized muscle weakness 58 31 frequent (33%) Frequent (79-30%) HP:0003324
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 muscle fiber atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0100295
23 central sleep apnea 58 31 frequent (33%) Frequent (79-30%) HP:0010536
24 bulbar palsy 58 31 frequent (33%) Frequent (79-30%) HP:0001283
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 dysphonia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001618
31 high palate 58 31 occasional (7.5%) Occasional (29-5%) HP:0000218
32 waddling gait 58 31 occasional (7.5%) Occasional (29-5%) HP:0002515
33 spinal rigidity 58 31 occasional (7.5%) Occasional (29-5%) HP:0003306
34 emg: myopathic abnormalities 58 31 occasional (7.5%) Occasional (29-5%) HP:0003458
35 toe walking 58 31 occasional (7.5%) Occasional (29-5%) HP:0040083
36 motor delay 58 31 occasional (7.5%) Occasional (29-5%) HP:0001270
37 kyphoscoliosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002751
38 long face 58 31 occasional (7.5%) Occasional (29-5%) HP:0000276
39 areflexia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001284
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 poor head control 58 31 occasional (7.5%) Occasional (29-5%) HP:0002421
43 weak cry 58 31 occasional (7.5%) Occasional (29-5%) HP:0001612
44 stridor 58 31 occasional (7.5%) Occasional (29-5%) HP:0010307
45 distal amyotrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0003693
46 limb-girdle muscle weakness 58 31 occasional (7.5%) Occasional (29-5%) HP:0003325
47 narrow jaw 58 31 occasional (7.5%) Occasional (29-5%) HP:0012801
48 seizure 31 occasional (7.5%) HP:0001250
49 hypotonia 31 occasional (7.5%) HP:0001252
50 nystagmus 58 31 very rare (1%) Very rare (<4-1%) HP:0000639

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 behavior/neurological MP:0005386 10.15 AGRN ALG2 CHAT CHRNA1 CHRNE COL13A1
2 growth/size/body region MP:0005378 10.1 AGRN ALG14 ALG2 CHAT CHRNE COL13A1
3 mortality/aging MP:0010768 10.1 AGRN ALG14 ALG2 CHAT CHRNA1 CHRNE
4 muscle MP:0005369 9.9 AGRN CHAT CHRNE COL13A1 DOK7 GFPT1
5 nervous system MP:0003631 9.77 AGRN ALG2 CHAT CHRNA1 CHRNB1 CHRNE
6 respiratory system MP:0005388 9.28 AGRN CHAT CHRNE DOK7 LRP4 MUSK
Sources

Drugs & Therapeutics for Congenital Myasthenic Syndrome

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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 Central Nervous System Stimulants Phase 1, Phase 2
4 Sympathomimetics Phase 1, Phase 2
5 Vasoconstrictor Agents Phase 1, Phase 2
6 Neurotransmitter Agents Phase 1
7 Adrenergic Agents Phase 1
8 Respiratory System Agents Phase 1
9 Anti-Asthmatic Agents Phase 1
10 Adrenergic beta-Agonists Phase 1
11 Albuterol Phase 1
12 Tocolytic Agents Phase 1
13 Bronchodilator Agents Phase 1
14 Adrenergic Agonists Phase 1
15
Amifampridine Approved, Investigational 54-96-6 5918
16 Potassium Channel Blockers

Interventional clinical trials:

(show all 11)
# 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 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
7 Treatment Use of 3,4 Diaminopyridine in Congenital Myasthenia and Lambert-Eaton Syndrome Available NCT03062631 3,4-Diaminopyridine
8 Treatment Use of 3,4-Diaminopyridine in Congenital Myasthenic Syndrome No longer available NCT01765140 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 3,4-Diaminopyridine for Lambert-Eaton Myasthenic Syndrome and Congenital Myasthenia No longer available NCT02012933 3,4-diaminopyridine
11 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

Sources

Genetic Tests for Congenital Myasthenic Syndrome

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Genetic tests related to Congenital Myasthenic Syndrome:

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

Anatomical Context for Congenital Myasthenic Syndrome

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MalaCards organs/tissues related to Congenital Myasthenic Syndrome:

40
Eye, Skeletal Muscle, Skin, Thymus, Thyroid, Uterus
Sources

Publications for Congenital Myasthenic Syndrome

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Articles related to Congenital Myasthenic Syndrome:

(show top 50) (show all 689)
# Title Authors PMID Year
1
Mutations in MUSK causing congenital myasthenic syndrome impair MuSK-Dok-7 interaction. 6 61 54 25
20371544 2010
2
CHRND mutation causes a congenital myasthenic syndrome by impairing co-clustering of the acetylcholine receptor with rapsyn. 54 25 6 61
16916845 2006
3
Congenital myasthenic syndromes. 25 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). 6 61 25 54
9758617 1998
5
Human endplate acetylcholinesterase deficiency caused by mutations in the collagen-like tail subunit (ColQ) of the asymmetric enzyme. 61 25 54 6
9689136 1998
6
Congenital Myasthenic Syndrome Type 19 Is Caused by Mutations in COL13A1, Encoding the Atypical Non-fibrillar Collagen Type XIII α1 Chain. 61 6 25
26626625 2015
7
Clinical and pathological heterogeneity of a congenital disorder of glycosylation manifesting as a myasthenic/myopathic syndrome. 25 61 6
24461433 2014
8
LRP4 third β-propeller domain mutations cause novel congenital myasthenia by compromising agrin-mediated MuSK signaling in a position-specific manner. 6 25 61
24234652 2014
9
Congenital myasthenic syndromes due to mutations in ALG2 and ALG14. 25 6 61
23404334 2013
10
Mutations in DPAGT1 cause a limb-girdle congenital myasthenic syndrome with tubular aggregates. 6 25 61
22742743 2012
11
LG2 agrin mutation causing severe congenital myasthenic syndrome mimics functional characteristics of non-neural (z-) agrin. 6 25 61
22205389 2012
12
Identification of an agrin mutation that causes congenital myasthenia and affects synapse function. 6 61 25
19631309 2009
13
Mutation analysis of CHRNA1, CHRNB1, CHRND, and RAPSN genes in multiple pterygium syndrome/fetal akinesia patients. 6 25 61
18179903 2008
14
MUSK, a new target for mutations causing congenital myasthenic syndrome. 6 61 25
15496425 2004
15
Mutation history of the roma/gypsies. 61 6 25
15322984 2004
16
The congenital myasthenic syndrome mutation RAPSN N88K derives from an ancient Indo-European founder. 61 6 25
15286164 2004
17
E-box mutations in the RAPSN promoter region in eight cases with congenital myasthenic syndrome. 6 25 61
12651869 2003
18
Choline acetyltransferase mutations cause myasthenic syndrome associated with episodic apnea in humans. 61 6 25
11172068 2001
19
Mutation causing congenital myasthenia reveals acetylcholine receptor beta/delta subunit interaction essential for assembly. 25 6 61
10562302 1999
20
A common mutation (epsilon1267delG) in congenital myasthenic patients of Gypsy ethnic origin. 61 6 25
10534268 1999
21
Mutation of the acetylcholine receptor epsilon-subunit promoter in congenital myasthenic syndrome. 61 6 25
10211467 1999
22
Mutant SNAP25B causes myasthenia, cortical hyperexcitability, ataxia, and intellectual disability. 25 6
25381298 2014
23
Synaptotagmin 2 mutations cause an autosomal-dominant form of lambert-eaton myasthenic syndrome and nonprogressive motor neuropathy. 25 6
25192047 2014
24
Hexosamine biosynthetic pathway mutations cause neuromuscular transmission defect. 25 6
21310273 2011
25
Refinement of the clinical phenotype in musk-related congenital myasthenic syndromes. 6 25
19949040 2009
26
Congenital myasthenic syndrome caused by two non-N88K rapsyn mutations. 6 61 54
17594401 2007
27
Impaired receptor clustering in congenital myasthenic syndrome with novel RAPSN mutations. 54 6 61
16931511 2006
28
Dok-7 mutations underlie a neuromuscular junction synaptopathy. 6 25
16917026 2006
29
Regulation of the rapsyn promoter by kaiso and delta-catenin. 6 54 61
15282317 2004
30
Rapsyn mutations in hereditary myasthenia: distinct early- and late-onset phenotypes. 6 25
14504330 2003
31
Myasthenic syndrome caused by mutation of the SCN4A sodium channel. 6 25
12766226 2003
32
Congenital myasthenic syndrome with episodic apnea in patients homozygous for a CHAT missense mutation. 61 54 6
12756141 2003
33
Identification of pathogenic mutations in the human rapsyn gene. 61 54 6
12730725 2003
34
Recessive inheritance and variable penetrance of slow-channel congenital myasthenic syndromes. 6 25
12141316 2002
35
Rapsyn mutations in humans cause endplate acetylcholine-receptor deficiency and myasthenic syndrome. 25 6
11791205 2002
36
Acetylcholine receptor delta subunit mutations underlie a fast-channel myasthenic syndrome and arthrogryposis multiplex congenita. 25 6
11435464 2001
37
Immature end-plates and utrophin deficiency in congenital myasthenic syndrome caused by epsilon-AChR subunit truncating mutations. 6 61 54
11030414 2000
38
Biallelic c.1263dupC in DOK7 results in fetal akinesia deformation sequence. 61 6
31880392 2020
39
Pathogenic effects of agrin V1727F mutation are isoform specific and decrease its expression and affinity for HSPGs and LRP4. 6 61
30994901 2019
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. 6 61
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. 61 6
18398509 2008
48
Clinical features of the DOK7 neuromuscular junction synaptopathy. 61 25 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 25 61
16009904 2005
Sources

Variations for Congenital Myasthenic Syndrome

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ClinVar genetic disease variations for Congenital Myasthenic Syndrome:

6 (show top 50) (show all 3308)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 RAPSN NM_005055.5(RAPSN):c.41T>C (p.Leu14Pro) SNV Pathogenic 8047 rs104894300 11:47470476-47470476 11:47448924-47448924
2 RAPSN RAPSN, 1-BP INS, 46C Insertion Pathogenic 8049
3 RAPSN NM_005055.5(RAPSN):c.807C>A (p.Tyr269Ter) SNV Pathogenic 8050 rs104894301 11:47463268-47463268 11:47441716-47441716
4 RAPSN NM_005055.5(RAPSN):c.193-15C>A SNV Pathogenic 8053 rs45547231 11:47469717-47469717 11:47448165-47448165
5 CHRNE NM_000080.4(CHRNE):c.721C>T (p.Leu241Phe) SNV Pathogenic 18352 rs28999110 17:4804366-4804366 17:4901071-4901071
6 CHRNB1 CHRNB1, 9-BP DEL, NT1276 Deletion Pathogenic 18374
7 CHRNB1 CHRNB1, EX8DEL Deletion Pathogenic 18375
8 CHRNA1 NM_001039523.3(CHRNA1):c.988G>A (p.Val330Ile) SNV Pathogenic 18382 rs137852804 2:175614763-175614763 2:174750035-174750035
9 CHRNA1 NM_001039523.3(CHRNA1):c.832T>G (p.Phe278Val) SNV Pathogenic 18383 rs137852805 2:175618252-175618252 2:174753524-174753524
10 CHRNA1 NM_001039523.3(CHRNA1):c.901T>C (p.Phe301Leu) SNV Pathogenic 18384 rs137852806 2:175614850-175614850 2:174750122-174750122
11 CHRNA1 NM_001039523.3(CHRNA1):c.529G>C (p.Val177Leu) SNV Pathogenic 18385 rs137852807 2:175619033-175619033 2:174754305-174754305
12 CHRNA1 CHRNA1, 1-BP DEL, 381C Deletion Pathogenic 18386
13 CHRNA1 CHRNA1, IVS3AS, G-A, -8 SNV Pathogenic 29581
14 MUSK NM_005592.4(MUSK):c.1031C>G (p.Pro344Arg) SNV Pathogenic 30175 rs387906803 9:113530210-113530210 9:110767930-110767930
15 CHRNE NM_000080.4(CHRNE):c.892_894del (p.Ser298del) Deletion Pathogenic 40227 rs398122830 17:4804111-4804113 17:4900816-4900818
16 MUSK NM_005592.4(MUSK):c.1815G>A (p.Met605Ile) SNV Pathogenic 60521 rs766640370 9:113550006-113550006 9:110787726-110787726
17 MUSK NM_005592.4(MUSK):c.2180C>T (p.Ala727Val) SNV Pathogenic 60522 rs397515450 9:113562838-113562838 9:110800558-110800558
18 SYT2 NM_177402.5(SYT2):c.920A>C (p.Asp307Ala) SNV Pathogenic 156368 rs587777781 1:202568479-202568479 1:202599351-202599351
19 CHRND NM_000751.3(CHRND):c.1204G>A (p.Glu402Lys) SNV Pathogenic 189817 rs145955590 2:233398797-233398797 2:232534087-232534087
20 CHRND CHRND, 2.2-KB DEL Deletion Pathogenic 189818
21 LRP4 NM_002334.4(LRP4):c.3697G>A (p.Glu1233Lys) SNV Pathogenic 189820 rs786205153 11:46897357-46897357 11:46875806-46875806
22 CHRNE NM_000080.4(CHRNE):c.764C>T (p.Ser255Leu) SNV Pathogenic 465864 rs1555546765 17:4804323-4804323 17:4901028-4901028
23 CHRNE NM_000080.4(CHRNE):c.1072_1091del (p.Pro358fs) Deletion Pathogenic 534252 rs932032926 17:4802621-4802640 17:4899326-4899345
24 CHRNE NM_000080.4(CHRNE):c.794del (p.Pro265fs) Deletion Pathogenic 567393 rs756675414 17:4804293-4804293 17:4900998-4900998
25 COL13A1 NM_001130103.2(COL13A1):c.1173del (p.Leu392fs) Deletion Pathogenic 218905 rs864309662 10:71682524-71682524 10:69922768-69922768
26 CHRNE NM_000080.4(CHRNE):c.794C>T (p.Pro265Leu) SNV Pathogenic 381628 rs759226183 17:4804293-4804293 17:4900998-4900998
27 CHRNE NC_000017.11:g.(?_4898726)_(4948404_?)del Deletion Pathogenic 833374 17:4802021-4851699
28 CHRNE NM_000080.4(CHRNE):c.1231C>T (p.Gln411Ter) SNV Pathogenic 835190 17:4802391-4802391 17:4899096-4899096
29 CHRNE NM_000080.4(CHRNE):c.835G>T (p.Val279Phe) SNV Pathogenic 841740 17:4804170-4804170 17:4900875-4900875
30 CHRNE NC_000017.11:g.(?_4901641)_(4903159_?)del Deletion Pathogenic 832659 17:4804936-4806454
31 CHRNE NM_000080.4(CHRNE):c.803-2A>G SNV Pathogenic 863073 17:4804204-4804204 17:4900909-4900909
32 CHRNE NM_000080.4(CHRNE):c.606_619del (p.Gly203fs) Deletion Pathogenic 863458 17:4804468-4804481 17:4901173-4901186
33 CHAT CHAT, 2-BP INS, 523CC Insertion Pathogenic 17505
34 CHAT NM_020549.4(CHAT):c.629T>C (p.Leu210Pro) SNV Pathogenic 17511 rs121912820 10:50828590-50828590 10:49620544-49620544
35 CHAT NM_020549.4(CHAT):c.1493C>T (p.Ser498Leu) SNV Pathogenic 17512 rs121912821 10:50857664-50857664 10:49649618-49649618
36 CHAT NM_020549.4(CHAT):c.1258C>T (p.Arg420Cys) SNV Pathogenic 17514 rs121912822 10:50854697-50854697 10:49646651-49646651
37 CHAT NM_020549.4(CHAT):c.669del (p.Gln223fs) Deletion Pathogenic 461462 rs1554802808 10:50828630-50828630 10:49620584-49620584
38 CHAT NM_020549.4(CHAT):c.1516G>T (p.Val506Leu) SNV Pathogenic 17508 rs121912817 10:50859934-50859934 10:49651888-49651888
39 CHAT NM_020549.4(CHAT):c.1642C>T (p.Arg548Ter) SNV Pathogenic 461449 rs369251527 10:50863148-50863148 10:49655102-49655102
40 CHRNE NM_000080.4(CHRNE):c.1371del (p.Cys458fs) Deletion Pathogenic 644142 rs1597612665 17:4802142-4802142 17:4898847-4898847
41 AGRN NM_198576.4(AGRN):c.1275C>G (p.Tyr425Ter) SNV Pathogenic 644955 rs1239736447 1:977433-977433 1:1042053-1042053
42 AGRN NM_198576.4(AGRN):c.902_912del (p.Arg301fs) Deletion Pathogenic 654128 rs1570193864 1:976719-976729 1:1041339-1041349
43 CHRNE NM_000080.4(CHRNE):c.361G>T (p.Gly121Ter) SNV Pathogenic 661902 rs1187421976 17:4805366-4805366 17:4902071-4902071
44 CHRNE NM_000080.4(CHRNE):c.684_687del (p.Asp229fs) Deletion Pathogenic 651789 rs1597619440 17:4804400-4804403 17:4901105-4901108
45 CHRNE NM_000080.4(CHRNE):c.854T>C (p.Val285Ala) SNV Pathogenic 803298 rs1597618787 17:4804151-4804151 17:4900856-4900856
46 CHRNE NM_000080.4(CHRNE):c.850A>C (p.Thr284Pro) SNV Pathogenic 18343 rs121909510 17:4804155-4804155 17:4900860-4900860
47 CHRNE NM_000080.4(CHRNE):c.1181_1187dup (p.Glu396delinsAspValTer) Duplication Pathogenic 465857 rs1423995073 17:4802524-4802525 17:4899229-4899230
48 CHRNE NM_000080.4(CHRNE):c.250del (p.Arg84fs) Deletion Pathogenic 465861 rs1555547003 17:4805606-4805606 17:4902311-4902311
49 CHRNE NM_000080.4(CHRNE):c.1380G>A (p.Trp460Ter) SNV Pathogenic 534250 rs1555546096 17:4802133-4802133 17:4898838-4898838
50 CHRNE NM_000080.4(CHRNE):c.918-1G>A SNV Pathogenic 582326 rs1407243713 17:4802878-4802878 17:4899583-4899583
Sources

Expression for Congenital Myasthenic Syndrome

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

Pathways for Congenital Myasthenic Syndrome

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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
Transmission across Chemical Synapses 65
Show member pathways
 12.68 SNAP25 CHRNE CHRND CHRNA1 CHAT
2
Synthesis of substrates in N-glycan biosythesis 65
Show member pathways
 11.84 GMPPB GFPT1 DPAGT1 ALG2 ALG14
3
N-Glycan biosynthesis 36
Show member pathways
 11.58 DPAGT1 ALG2 ALG14
4
Postsynaptic nicotinic acetylcholine receptors 65
Show member pathways
 11.45 CHRNE CHRND CHRNA1
5
ECM proteoglycans 65
11.19 MUSK LRP4 AGRN
6
Agrin Interactions at Neuromuscular Junction 63
11.01 RAPSN MUSK CHRNA1 AGRN
7
Effects of Botulinum toxin 1
10.28 SNAP25 CHRNA1
8
Succinylcholine Pathway, Pharmacokinetics/Pharmacodynamics 60
10 CHRNE CHRND CHRNB1 CHRNA1
Sources

GO Terms for Congenital Myasthenic Syndrome

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

# Name GO ID Score Top Affiliating Genes
1 membrane GO:0016020 10.33 SNAP25 SCN4A RAPSN MUSK LRP4 DPAGT1
2 integral component of membrane GO:0016021 10.26 SCN4A MUSK LRP4 DPAGT1 COL13A1 CHRNE
3 plasma membrane GO:0005886 10.25 SNAP25 SCN4A RAPSN MUSK LRP4 DOK7
4 cell junction GO:0030054 9.9 SNAP25 RAPSN MUSK DOK7 COLQ COL13A1
5 neuron projection GO:0043005 9.85 SNAP25 CHRNE CHRND CHRNB1 CHRNA1 CHAT
6 postsynaptic membrane GO:0045211 9.8 RAPSN MUSK COL13A1 CHRNE CHRND CHRNB1
7 synapse GO:0045202 9.73 SNAP25 RAPSN MUSK DOK7 COLQ COL13A1
8 acetylcholine-gated channel complex GO:0005892 9.62 CHRNE CHRND CHRNB1 CHRNA1
9 integral component of postsynaptic specialization membrane GO:0099060 9.58 CHRND CHRNB1 CHRNA1
10 neuromuscular junction GO:0031594 9.23 RAPSN MUSK LRP4 COLQ CHRNE CHRND

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

(show all 22)
# Name GO ID Score Top Affiliating Genes
1 ion transport GO:0006811 9.98 SCN4A CHRNE CHRND CHRNB1 CHRNA1
2 ion transmembrane transport GO:0034220 9.88 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 chemical synaptic transmission GO:0007268 9.8 SNAP25 RAPSN CHRNE CHRND CHRNB1 CHRNA1
6 cation transport GO:0006812 9.74 CHRND CHRNB1 CHRNA1
7 excitatory postsynaptic potential GO:0060079 9.73 CHRNE CHRND CHRNB1 CHRNA1
8 nervous system process GO:0050877 9.71 CHRNE CHRND CHRNB1 CHRNA1
9 skeletal muscle contraction GO:0003009 9.67 CHRND CHRNB1 CHRNA1
10 regulation of postsynaptic membrane potential GO:0060078 9.67 CHRNE CHRND CHRNB1 CHRNA1
11 neuromuscular synaptic transmission GO:0007274 9.65 CHRNB1 CHRNA1 CHAT
12 dolichol-linked oligosaccharide biosynthetic process GO:0006488 9.63 DPAGT1 ALG2 ALG14
13 neuronal action potential GO:0019228 9.61 SCN4A CHRNA1
14 receptor clustering GO:0043113 9.6 LRP4 AGRN
15 neuromuscular process GO:0050905 9.59 CHRND CHRNA1
16 UDP-N-acetylglucosamine metabolic process GO:0006047 9.56 GFPT1 DPAGT1
17 musculoskeletal movement GO:0050881 9.55 CHRND CHRNA1
18 skeletal muscle tissue growth GO:0048630 9.54 CHRND CHRNA1
19 neuromuscular junction development GO:0007528 9.46 MUSK DOK7 CHRNA1 AGRN
20 skeletal muscle acetylcholine-gated channel clustering GO:0071340 9.43 MUSK LRP4 COLQ
21 regulation of synaptic growth at neuromuscular junction GO:0008582 9.13 MUSK COLQ AGRN
22 synaptic transmission, cholinergic GO:0007271 8.92 RAPSN CHRNE 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 matrix structural constituent GO:0005201 9.63 COLQ COL13A1 AGRN
5 acetylcholine receptor activity GO:0015464 9.5 CHRNE CHRNB1 CHRNA1
6 extracellular ligand-gated ion channel activity GO:0005230 9.46 CHRNE CHRND CHRNB1 CHRNA1
7 acetylcholine binding GO:0042166 9.43 CHRND CHRNB1 CHRNA1
8 transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential GO:1904315 9.26 CHRNE CHRND CHRNB1 CHRNA1
9 acetylcholine-gated cation-selective channel activity GO:0022848 8.92 CHRNE CHRND CHRNB1 CHRNA1
Sources

Sources for Congenital Myasthenic Syndrome

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3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
The MalaCards human disease database index: 1-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
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