Congenital Myasthenic Syndrome malady

Genetics Home Reference: 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.¹⁷

MalaCards: Congenital Myasthenic Syndrome, also known as congenital myasthenia, is related to lambert-eaton myasthenic syndrome and slow-channel congenital myasthenic syndrome. An important gene associated with Congenital Myasthenic Syndrome is CHRND (cholinergic receptor, nicotinic, delta (muscle)), and among its related pathways are Highly sodium permeable acetylcholine nicotinic receptors and Sympathetic Nerve Pathway (Pre- and Post- Ganglionic Junction). The compounds alpha-bungarotoxin and alpha-conotoxin ei have been mentioned in the context of this disorder. Affiliated tissues include skeletal muscle, and related mouse phenotypes are respiratory system and muscle.

NINDS: 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.³¹

Wikipedia: Congenital myasthenic syndrome (CMS) is an inherited neuromuscular disorder caused by defects of several...⁴⁴ more...

GeneReviews summary for cms

Aliases & Descriptions:

congenital myasthenic syndrome 6 17 8 congenital myasthenia 15 16 31 43 congenital myasthenic syndromes 15 16 lambert-eaton myasthenic syndrome 43 myasthenic syndromes, congenital 43

myasthenic syndromes congenital 32 myasthenia - congenital 31 myasthenias 43 cms 17

Diseases related to congenital myasthenic syndrome by text searches and GeneDecks gene sharing:

(show top 50)    (show all 190)

id	Related Disease	Score	Top Affiliating Genes
1	lambert-eaton myasthenic syndrome	37.8	RAPSN, MUSK, CACNA1A
2	slow-channel congenital myasthenic syndrome	33.7	CHRND, CHRNB1, CHRNE
3	congenital myasthenic syndrome associated with acetylcholine receptor deficiency	30.9	CHRNB1, MUSK, RAPSN, CHRNE
4	myasthenic syndrome, fast-channel congenital	30.1	CHRND, CHRNE
5	myasthenic syndrome	29.8	BLZF1, UTRN, RAPSN, VPS13C, CHRNE, CHRNB1
6	myasthenia, limb-girdle, familial	29.6	DOK7, AGRN
7	arthrogryposis	29.5	CHRNG, CHRND, RAPSN
8	respiratory failure	28.1	CHAT, MUSK, ACHE
9	ataxia	26.8	ACHE, LAMB2, BLZF1, PTBP1, CACNA1A, AGRN
10	neuromuscular disease	26.3	SCN4A, UTRN, MUSK
11	myasthenia gravis	26.2	CHRNG, CHRNE, AGRN, RAPSN, UTRN, CHRND
12	nystagmus	26.2	ACHE, CACNA1A, LAMB2
13	ptosis	25.6	CHRNB1, CHRNE, ACHE, LAMB2, CHRND, CHRNG
14	dementia	24.1	CACNA1A, PTBP1, COLQ, ACHE, CHAT
15	neuropathy	24.0	SCN4A, CHRNB1, CHAT, ACHE, DOK7, CACNA1A
16	myopathy	23.2	SCN4A, BLZF1, UTRN, CHAT, CHRNE, CACNA1A
17	multiple pterygium syndrome lethal type	13.4	CHRNG, CHRND
18	endplate acetylcholinesterase deficiency	13.2	ACHE, COLQ
19	lymphangioma	13.2	CHRND, CHRNG, CHRNB1
20	episodic ataxia	13.1	MUSK, ACHE
21	cystic lymphangioma	13.0	CHRND, CHRNB1, CHRNG, RAPSN
22	fetal akinesia deformation sequence	13.0	CHRND, DOK7, RAPSN, CHRNG
23	ophthalmoplegia	13.0	CHRND, LAMB2, CHRNB1, CHRNE
24	multiple pterygium syndrome escobar type	13.0	RAPSN, CHRNG, CHRNB1, CHRND
25	amnestic disorder	12.9	CHAT, ACHE
26	spinocerebellar ataxia type 6	12.9	BLZF1, CACNA1A
27	nicotine dependence	12.8	CHRNE, CHRNG, CHRND, CHRNB1, CHAT
28	hypotonia	12.8	CHRND, CHRNE, LAMB2, CHRNB1
29	vascular dementia	12.7	COLQ, ACHE, CHAT
30	spinal muscular atrophy	12.6	UTRN, BLZF1, CHAT
31	muscular dystrophy	12.5	UTRN, MUSK, LAMB2, AGRN
32	paralysis	12.4	MUSK, CACNA1A, ACHE, SCN4A
33	prion disease	12.3	BLZF1, CHAT, LAMB2, ACHE, AGRN
34	huntington's disease	12.3	ACHE, CACNA1A, CHAT
35	thymoma	9.7
36	neuronitis	9.6	CACNA1A, LAMB2, CHAT, CHRND, BLZF1, UTRN
37	carcinoma	9.3
38	lung cancer	9.3
39	congenital myasthenic syndrome with episodic apnea	8.9
40	agrn-related congenital myasthenic syndrome	8.4
41	cerebellar degeneration	8.4
42	lung carcinoma	8.4
43	myasthenia	8.4
44	myasthenic syndrome, congenital, associated with facial dysmorphism and acetylcholine receptor deficiency	8.4
45	paraneoplastic cerebellar degeneration	8.4
46	paraneoplastic neurologic disorders	8.4
47	paraneoplastic syndromes	8.4
48	small cell carcinoma	8.4
49	apnea	8.0
50	musk-related congenital myasthenic syndrome	8.0

Approved drugs:

Drug clinical trials:

Genetic tests related to congenital myasthenic syndrome:

id	Genetic test	Affiliating Genes
1	Congenital Myasthenic Syndrome clinical/research	RAPSN, SCN4A, CHRND, CHAT, CHRNA1, MUSK, DOK7, COLQ, AGRN, GFPT1 (show all 12) CHRNB1, CHRNE

MalaCards organs/tissues related to congenital myasthenic syndrome:

²²

MGI Mouse Phenotypes related to congenital myasthenic syndrome:

²⁵

id	Description	MGI Source Accession	Score	Top Affiliating Genes
1	respiratory system phenotype	MP:0005388	7.5	CHRNG, CHRNE, AGRN, ACHE, DOK7, CACNA1A
2	muscle phenotype	MP:0005369	7.4	RAPSN, CHRNG, CHRNE, AGRN, ACHE, CACNA1A
3	growth/size phenotype	MP:0005378	6.9	CHRNE, AGRN, ACHE, COLQ, CACNA1A, LAMB2
4	behavior/neurological phenotype	MP:0005386	6.7	COLQ, ACHE, AGRN, CHRNE, CHRNG, DOK7
5	nervous system phenotype	MP:0003631	6.6	ACHE, AGRN, CHRNB1, CHRNE, CHRNG, COLQ
6	mortality/aging	MP:0010768	6.2	COLQ, ACHE, AGRN, CHRNE, CHRNG, DOK7

Articles related to congenital myasthenic syndrome:

(show top 50)    (show all 68)

id	Title	Authors	Year	Affiliating Genes
1	Congenital myasthenic syndrome due to homozygous CHRN E mutations: report of patients in Arabia. (21150643)	Salih M.A.... Bosley T.M.	2011	CHRNE
2	Diagnosis of congenital myasthenic syndrome with muta tion of the RAPSN gene after general anaesthesia. (21372719)	Gentili A.... Baroncini S.	2011	RAPSN
3	Congenital stridor with feeding difficulty as a prese nting symptom of Dok7 congenital myasthenic syndrome. (20554332)	Jephson C.G.... Bailey C.M.	2010	DOK7
4	Intra-familial variation in clinical manifestations a nd response to ephedrine in siblings with congenital myasthenic syndrome caused by novel COLQ mutations. (20370815)	Yeung W.L.... Ng P.C.	2010	COLQ
5	Treatment approach to congenital myasthenic syndrome in a patient with acetylcholine receptor deficiency (19172815)	Ishigaki K.... Osawa M.	2009	RAPSN
6	Tannic acid facilitates expression of the polypyrimidine tract binding protein and alleviates deleterious inclusion of CHRNA1 exon P3A due to an hnRNP H-disrupting mutation in congenital myasthenic syndrome. (19147685)	Bian Y.... Ohno K.	2009	CHRNA1, PTBP1
7	Congenital myasthenic syndrome with episodic apnea. (19520274)	Mallory L.A.... Kang P.B.	2009	CHAT
8	Mutations in LAMB2 causing a severe form of synaptic congenital myasthenic syndrome. (19251977)	Maselli R.A.... Wollmann R.L.	2009	LAMB2
9	Refinement of the clinical phenotype in musk-related congenital myasthenic syndromes. (19949040)	Mihaylova V.... Guergueltcheva V.	2009	MUSK
10	Dok-7/MuSK signaling and a congenital myasthenic syndrome. (19108574)	Yamanashi Y.... Beeson D.	2008	MUSK, DOK7
11	Congenital myasthenic syndromes in childhood: diagnostic and management challenges. (18707767)	Kinali M.... Robb S.A.	2008	COLQ, DOK7
12	Clinical and molecular genetic findings in COLQ-mutant congenital myasthenic syndromes. (18180250)	Mihaylova V.... Lochmuller H.	2008	COLQ, DOK7
13	Further observations in congenital myasthenic syndromes. (18567859)	Engel A.G.... Sine S.M.	2008	ACHE, CHAT, MUSK
14	Novel COLQ mutation 950delC in synaptic congenital myasthenic syndrome and symptomatic heterozygous relatives. (17300939)	Schreiner F.... Woelfle J.	2007	ACHE, COLQ
15	Phenotypical spectrum of DOK7 mutations in congenital myasthenic syndromes. (17439981)	Muller J.S.... Lochmuller H.	2007	BLZF1, DOK7
16	A synonymous CHRNE mutation responsible for an aberrant splicing leading to congenital myasthenic syndrome. (17363247)	Richard P.... Eymard B.	2007	CHRNE
17	CHRND mutation causes a congenital myasthenic syndrome by impairing co-clustering of the acetylcholine receptor with rapsyn. (16916845)	Muller J.S.... Abicht A.	2006	CHRND, RAPSN
18	Impaired receptor clustering in congenital myasthenic syndrome with novel RAPSN mutations. (16931511)	Mueller J.S.... Lochmueller H.	2006	RAPSN
19	Towards the molecular elucidation of congenital myasthenic syndromes: identification of mutations in MuSK. (16550915)	Chevessier F.... Hantai D.	2005	MUSK
20	Pathophysiological characterization of congenital myasthenic syndromes: the example of mutations in the MUSK gene (16114265)	Chevessier F.... Hantai D.	2005	MUSK
21	Current understanding of congenital myasthenic syndromes. (15907919)	Engel A.G.... Sine S.M.	2005	CHAT, MUSK, RAPSN
22	An intronic base alteration of the CHRNE gene leading to a congenital myasthenic syndrome. (16087917)	Muller J.S.... Abicht A.	2005	CHRNE
23	MUSK, a new target for mutations causing congenital myasthenic syndrome. (15496425)	Chevessier F.... Hantai D.	2004	MUSK
24	Congenital myasthenic syndrome due to rapsyn deficiency: three cases with arthrogryposis and bulbar symptoms. (15328566)	Ioos C.... Estournet-Mathiaud B.	2004	RAPSN
25	Mutation in the AChR ion channel gate underlies a fast channel congenital myasthenic syndrome. (15079006)	Webster R.... Beeson D.	2004	CHRNA1
26	Electrophysiological and morphological characterization of a case of autosomal recessive congenital myasthenic syndrome with acetylcholine receptor deficiency due to a N88K rapsyn homozygous mutation. (14659409)	Yasaki E.... Hantai D.	2004	RAPSN
27	Novel truncating RAPSN mutations causing congenital myasthenic syndrome responsive to 3,4-diaminopyridine. (15036330)	Banwell B.L.... Engel A.G.	2004	RAPSN
28	Congenital myasthenic syndromes. (15367858)	Hantai D.... Eymard B.	2004	ACHE, CHAT, RAPSN
29	Congenital myasthenic syndromes due to mutations in the rapsyn gene (15269664)	Eymard B.... Hantai D.	2004	RAPSN
30	Congenital myasthenic syndrome: presentation, electrodiagnosis, and muscle biopsy. (15119478)	Gurnett C.A.... Connolly A.M.	2004	ACHE
31	Congenital myasthenic syndromes: phenotypic expression and pathophysiological characterisation (15034473)	Andreux F.... Eymard B.	2004	RAPSN
32	Congenital myasthenic syndromes: multiple molecular targets at the neuromuscular junction. (14592871)	Engel A.G.... Sine S.M.	2003	RAPSN
33	Congenital myasthenic syndrome due to a novel missense mutation in the gene encoding choline acetyltransferase. (12609506)	Schmidt C.... Lochmuller H.	2003	CHAT
34	Rapsyn N88K is a frequent cause of congenital myasthenic syndromes in European patients. (12796535)	Mueller J.S.... Abicht A.	2003	RAPSN
35	Possible founder effect of rapsyn N88K mutation and identification of novel rapsyn mutations in congenital myasthenic syndromes. (12807980)	Richard P.... Hantai D.	2003	RAPSN
36	Congenital myasthenic syndrome with episodic apnea in patients homozygous for a CHAT missense mutation. (12756141)	Kraner S.... Steinlein O.K.	2003	CHAT
37	Structural abnormalities of the AChR caused by mutations underlying congenital myasthenic syndromes. (14592868)	Beeson D.... Vincent A.	2003	CHRNE
38	Congenital myasthenic syndromes: A diverse array of molecular targets. (15034283)	Engel A.G.... Sine S.M.	2003	RAPSN
39	Congenital myasthenic syndromes: genetic defects of t he neuromuscular junction. (11898587)	Ohno K.... Engel A.G.	2002	CHAT
40	Congenital myasthenic syndrome caused by low-expressor fast-channel AChR delta subunit mutation. (12499478)	Shen X.-M.... Engel A.G.	2002	CHRND
41	Presynaptic congenital myasthenic syndrome due to qua ntal release deficiency. (11468313)	Maselli R.A.... Wollmann R.L.	2001	CACNA1A
42	Immature end-plates and utrophin deficiency in congenital myasthenic syndrome caused by epsilon-AChR subunit truncating mutations. (11030414)	Sieb J.P.... Steinlein O.K.	2000	UTRN, CHRNE
43	Fundamental gating mechanism of nicotinic receptor channel revealed by mutation causing a congenital myasthenic syndrome. (10962020)	Wang H.-L.... Sine S.M.	2000	CHRNE
44	Novel functional epsilon-subunit polypeptide generated by a single nucleotide deletion in acetylcholine receptor deficiency congenital myasthenic syndrome. (10514102)	Croxen R.... Beeson D.	1999	CHRNE
45	Congenital myasthenic syndromes in two kinships with end-plate acetylcholine receptor and utrophin deficiency. (9443457)	Sieb J.P.... Ries F.	1998	UTRN
46	Mutation in the human acetylcholinesterase-associated collagen gene, COLQ, is responsible for congenital myasthenic syndrome with end-plate acetylcholinesterase deficiency (Type Ic). (9758617)	Donger C.... Guicheney P.	1998	ACHE, COLQ
47	Mutations in different functional domains of the human muscle acetylcholine receptor alpha subunit in patients with the slow-channel congenital myasthenic syndrome. (9158151)	Croxen R.... Newsom-Davis J.	1997	CHRNA1
48	Congenital myasthenic syndrome caused by decreased agonist binding affinity due to a mutation in the acetylcholine receptor epsilon subunit. (8755487)	Ohno K.... Engel A.G.	1996	CHRNE
49	New mutations in acetylcholine receptor subunit genes reveal heterogeneity in the slow-channel congenital myasthenic syndrome. (8872460)	Engel A.G.... Sine S.M.	1996	CHRND, CHRNA1, CHRNB1
50	Congenital myasthenic syndrome caused by prolonged acetylcholine receptor channel openings due to a mutation in the M2 domain of the epsilon subunit. (7531341)	Ohno K.... Engel A.G.	1995	CHRNE

Genes related to congenital myasthenic syndrome according to GeneCards:

(show all 21)

id	Symbol	Description	Score	GeneCards Section Context
1	CHRND	cholinergic receptor, nicotinic, delta (muscle)	11.1	Summaries, Publications
2	CHRNE	cholinergic receptor, nicotinic, epsilon (muscle)	11.1	Summaries, Publications
3	RAPSN	receptor-associated protein of the synapse	11.1	Summaries, Publications, Orthologs
4	CHRNB1	cholinergic receptor, nicotinic, beta 1 (muscle)	11.1	Publications, Summaries
5	MUSK	muscle, skeletal, receptor tyrosine kinase	11.1	Summaries, Publications
6	CHAT	choline O-acetyltransferase	11.1	Summaries, Publications
7	DOK7	docking protein 7	11.1	Publications, Summaries
8	AGRN	agrin	11.1	Summaries
9	COLQ	collagen-like tail subunit (single strand of homotrimer) of asymmetric acetylcholinesterase	11.0	Publications
10	SCN4A	sodium channel, voltage-gated, type IV, alpha subunit	11.0
11	CHRNG	cholinergic receptor, nicotinic, gamma (muscle)	11.0
12	RPL14	ribosomal protein L14	11.0
13	LAMB2	laminin, beta 2 (laminin S)	11.0	Publications
14	GFPT1	glutamine--fructose-6-phosphate transaminase 1	11.0
15	BLZF1	basic leucine zipper nuclear factor 1	11.0	Publications
16	ACHE	acetylcholinesterase	11.0	Publications
17	PTBP1	polypyrimidine tract binding protein 1	11.0	Publications
18	UTRN	utrophin	11.0	Publications
19	CACNA1A	calcium channel, voltage-dependent, P/Q type, alpha 1A subunit	11.0	Publications
20	VPS13C	vacuolar protein sorting 13 homolog C (S. cerevisiae)	11.0
21	CHRNA1	cholinergic receptor, nicotinic, alpha 1 (muscle)	10.4	Publications

Pathways related to congenital myasthenic syndrome according to GeneDecks:

id	Pathway	Score	Top Affiliating Genes
1	Highly sodium permeable acetylcholine nicotinic receptors38	10.0	CHRNG, CHRNE, CHRND
2	Sympathetic Nerve Pathway (Pre- and Post- Ganglionic Junction)34	9.7	ACHE, CHAT
3	eNOS Signaling36	9.5	CHRND, MUSK, CHRNB1, CHRNE, CHRNG
4	Agrin Interactions at Neuromuscular Junction36	9.5	AGRN, MUSK, UTRN, RAPSN
5	Neuroactive ligand-receptor interaction20	9.3	CHRND, CHRNB1, CHRNE, CHRNG
6	Sympathetic Nerve Pathway (Neuroeffector Junction)34	9.3	ACHE, CACNA1A, CHAT
7	Cholinergic synapse20	9.2	CHAT, CACNA1A, ACHE
8	Calcium channels10	9.2	CHRND, CACNA1A, CHRNB1, CHRNE, CHRNG
9	Intracellular Calcium Signaling36	9.0	CHRND, MUSK, CACNA1A, CHRNE, CHRNG

Compounds related to congenital myasthenic syndrome according to GeneDecks:

(show all 24)

id	Compound	Score	Top Affiliating Genes
1	alpha-bungarotoxin32	10.3	CHAT, AGRN
2	alpha-conotoxin ei42	10.2	CHRND, CHRNB1, CHRNG
3	af 64a32	10.2	CHAT, ACHE
4	edrophonium32 9 9	12.1	MUSK, ACHE
5	mecamylamine hydrochloride42	10.1	CHRNG, CHRNE, CHRNB1
6	(+-)-anatoxin a fumarate42	10.1	CHRNG, CHRNE, CHRNB1
7	(+-)-epibatidine42	10.1	CHRNG, CHRNE, CHRNB1
8	muscarine32	10.1	ACHE, CHAT
9	huperzine a32	10.1	CHAT, ACHE
10	physostigmine32 9 9	12.1	CHAT, ACHE
11	chlorpyrifos32	10.0	ACHE, CHAT
12	carbamate32	10.0	CHAT, ACHE
13	succinylcholine32 9 9	11.9	SCN4A, ACHE
14	donepezil32 9 18 9	12.8	ACHE, CHAT
15	pirenzepine32 9 9	11.8	CHAT, ACHE
16	pyridostigmine32 9 9	11.7	CHAT, ACHE
17	nicotine32 34 9 9	12.6	AGRN, ACHE, MUSK, CHAT
18	phosphotyrosine32	9.3	MUSK, BLZF1, UTRN, RAPSN
19	acetazolamide32 9 9	11.3	SCN4A, CACNA1A
20	galantamine32 34 9 9	12.0	CHRNG, CHRNE, CHRNB1, ACHE, CHRNA1, CHRND
21	potassium32 9 18 9	11.9	CACNA1A, MUSK, CHAT, SCN4A, BLZF1, RAPSN
22	sodium32 18	9.9	AGRN, CACNA1A, CHAT, SCN4A, BLZF1, RAPSN
23	calcium32 9 18 9	10.6	AGRN, CACNA1A, LAMB2, MUSK, CHAT, SCN4A
24	acetylcholine32 9 18 9	10.5	RAPSN, AGRN, ACHE, CACNA1A, LAMB2, MUSK

Cellular components related to congenital myasthenic syndrome according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	synaptic cleft	GO:043083	9.5	ACHE, COLQ
2	acetylcholine-gated channel complex	GO:005892	9.4	CHRNE, CHRNB1, CHRNA1, CHRND
3	basal lamina	GO:005605	9.3	AGRN, ACHE, COLQ, LAMB2
4	neuromuscular junction	GO:031594	9.2	RAPSN, CHRNA1, MUSK, DOK7
5	postsynaptic membrane	GO:045211	8.3	CHRNG, CHRNE, CHRNB1, MUSK, CHRNA1, CHRND
6	cell junction	GO:030054	7.4	RAPSN, CHRNG, CHRNE, CHRNB1, ACHE, COLQ
7	plasma membrane	GO:005886	7.1	CHRNE, AGRN, ACHE, DOK7, CACNA1A, CHRNA1

Biological processes related to congenital myasthenic syndrome according to GeneDecks:

(show all 8)

id	Name	GO ID	Score	Top Affiliating Genes
1	synaptic transmission, cholinergic	GO:007271	10.0	CHRNE, CHRNB1, RAPSN
2	regulation of membrane potential	GO:042391	9.9	CHRND, CHRNB1, CHRNE
3	neuromuscular junction development	GO:007528	9.6	DOK7, LAMB2, MUSK
4	acetylcholine catabolic process in synaptic cleft	GO:001507	9.5	COLQ, ACHE
5	neuromuscular synaptic transmission	GO:007274	9.5	CHAT, CACNA1A, CHRNB1
6	receptor clustering	GO:043113	9.4	CACNA1A, DOK7, AGRN
7	muscle contraction	GO:006936	9.0	UTRN, SCN4A, CHRND, CHRNB1, CHRNE, CHRNG
8	synaptic transmission	GO:007268	8.5	CHRNG, CHRNE, ACHE, CACNA1A, CHAT, CHRND

Molecular functions related to congenital myasthenic syndrome according to GeneDecks:

id	Name	GO ID	Score	Top Affiliating Genes
1	laminin binding	GO:043236	9.8	ACHE, AGRN
2	acetylcholine receptor activity	GO:015464	9.7	CHRNG, CHRNE, CHRNB1
3	channel activity	GO:015267	9.7	CHRNB1, CHRNG
4	acetylcholine-activated cation-selective channel activity	GO:004889	9.7	CHRND, CHRNB1, CHRNE, CHRNG
5	acetylcholine binding	GO:042166	9.7	CHRNB1, ACHE, CHRND