KEGG DISEASE: Congenital myasthenic syndrome

DISEASE: Congenital myasthenic syndrome

Entry

H00770                      Disease

Name

Congenital myasthenic syndrome

Description

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.

Category

Nervous system disease

Brite

Human diseases in ICD-11 classification [BR:br08403]
08 Diseases of the nervous system
  Diseases of neuromuscular junction or muscle
   Myasthenia gravis or certain specified neuromuscular junction disorders
    8C61  Congenital myasthenic syndromes
     H00770  Congenital myasthenic syndrome
Pathway-based classification of diseases [BR:br08402]
Cellular process
  nt06539  Cytoskeleton in muscle cells
   H00770  Congenital myasthenic syndrome
  nt06544  Neuroactive ligand signaling
   H00770  Congenital myasthenic syndrome

Pathway

hsa04820

Cytoskeleton in muscle cells

hsa04725

Cholinergic synapse

hsa04082

Neuroactive ligand signaling

hsa04080

Neuroactive ligand-receptor interaction

hsa00510

N-Glycan biosynthesis

hsa04721

Synaptic vesicle cycle

hsa00513

Various types of N-glycan biosynthesis

Network

nt06539 Cytoskeleton in muscle cells
nt06544 Neuroactive ligand signaling

Gene

(CMS1A/1B) CHRNA1 [HSA:1134] [KO:K04803]
(CMS2A/2C) CHRNB1 [HSA:1140] [KO:K04812]
(CMS3A/3B/3C) CHRND [HSA:1144] [KO:K04816]
(CMS4A/4B/4C) CHRNE [HSA:1145] [KO:K04817]
(CMS5) COLQ [HSA:8292] [KO:K26586]
(CMS6) CHAT [HSA:1103] [KO:K00623]
(CMS7A/7B) SYT2 [HSA:127833] [KO:K19902]
(CMS8) AGRN [HSA:375790] [KO:K06254]
(CMS9) MUSK [HSA:4593] [KO:K05129]
(CMS10) DOK7 [HSA:285489] [KO:K24038]
(CMS11) RAPSN [HSA:5913] [KO:K24924]
(CMS12) GFPT1 [HSA:2673] [KO:K00820]
(CMS13) DPAGT1 [HSA:1798] [KO:K01001]
(CMS14) ALG2 [HSA:85365] [KO:K03843]
(CMS15) ALG14 [HSA:199857] [KO:K07441]
(CMS16) SCN4A [HSA:6329] [KO:K04837]
(CMS17) LRP4 [HSA:4038] [KO:K20051]
(CMS19) COL13A1 [HSA:1305] [KO:K16617]
(CMS20) SLC5A7 [HSA:60482] [KO:K14387]
(CMS21) SLC18A3 [HSA:6572] [KO:K14636]
(CMS22) PREPL [HSA:9581] [KO:K22582]
(CMS23) SLC25A1 [HSA:6576] [KO:K15100]
(CMS24) MYO9A [HSA:4649] [KO:K10360]
(CMS25) VAMP1 [HSA:6843] [KO:K08510]

Other DBs

ICD-11:

8C61

MeSH:

D020294

Reference

PMID:19593127

Authors

Argov Z

Title

Management of myasthenic conditions: nonimmune issues.

Journal

Curr Opin Neurol 22:493-7 (2009)
DOI:10.1097/WCO.0b013e32832f15fa

Reference

PMID:20547629

Authors

Spillane J, Beeson DJ, Kullmann DM

Title

Myasthenia and related disorders of the neuromuscular junction.

Journal

J Neurol Neurosurg Psychiatry 81:850-7 (2010)
DOI:10.1136/jnnp.2008.169367

Reference

PMID:8872460 (CMS1A CMS2A CMS4A)

Authors

Engel AG, Ohno K, Milone M, Wang HL, Nakano S, Bouzat C, Pruitt JN 2nd, Hutchinson DO, Brengman JM, Bren N, Sieb JP, Sine SM

Title

New mutations in acetylcholine receptor subunit genes reveal heterogeneity in the slow-channel congenital myasthenic syndrome.

Journal

Hum Mol Genet 5:1217-27 (1996)
DOI:10.1093/hmg/5.9.1217

Reference

PMID:10195214 (CMS1B)

Authors

Wang HL, Milone M, Ohno K, Shen XM, Tsujino A, Batocchi AP, Tonali P, Brengman J, Engel AG, Sine SM

Title

Acetylcholine receptor M3 domain: stereochemical and volume contributions to channel gating.

Journal

Nat Neurosci 2:226-33 (1999)
DOI:10.1038/6326

Reference

PMID:10562302 (CMS2C)

Authors

Quiram PA, Ohno K, Milone M, Patterson MC, Pruitt NJ, Brengman JM, Sine SM, Engel AG

Title

Mutation causing congenital myasthenia reveals acetylcholine receptor beta/delta subunit interaction essential for assembly.

Journal

J Clin Invest 104:1403-10 (1999)
DOI:10.1172/JCI8179

Reference

PMID:11782989 (CMS3A)

Authors

Gomez CM, Maselli RA, Vohra BP, Navedo M, Stiles JR, Charnet P, Schott K, Rojas L, Keesey J, Verity A, Wollmann RW, Lasalde-Dominicci J

Title

Novel delta subunit mutation in slow-channel syndrome causes severe weakness by novel mechanisms.

Journal

Ann Neurol 51:102-12 (2002)
DOI:10.1002/ana.10077

Reference

PMID:11435464 (CMS3B)

Authors

Brownlow S, Webster R, Croxen R, Brydson M, Neville B, Lin JP, Vincent A, Newsom-Davis J, Beeson D

Title

Acetylcholine receptor delta subunit mutations underlie a fast-channel myasthenic syndrome and arthrogryposis multiplex congenita.

Journal

J Clin Invest 108:125-30 (2001)
DOI:10.1172/JCI12935

Reference

PMID:16916845 (CMS3C)

Authors

Muller JS, Baumeister SK, Schara U, Cossins J, Krause S, von der Hagen M, Huebner A, Webster R, Beeson D, Lochmuller H, Abicht A

Title

CHRND mutation causes a congenital myasthenic syndrome by impairing co-clustering of the acetylcholine receptor with rapsyn.

Journal

Brain 129:2784-93 (2006)
DOI:10.1093/brain/awl188

Reference

PMID:8755487 (CMS4B)

Authors

Ohno K, Wang HL, Milone M, Bren N, Brengman JM, Nakano S, Quiram P, Pruitt JN, Sine SM, Engel AG

Title

Congenital myasthenic syndrome caused by decreased agonist binding affinity due to a mutation in the acetylcholine receptor epsilon subunit.

Journal

Neuron 17:157-70 (1996)
DOI:10.1016/s0896-6273(00)80289-5

Reference

PMID:8957026 (CMS4C)

Authors

Engel AG, Ohno K, Bouzat C, Sine SM, Griggs RC

Title

End-plate acetylcholine receptor deficiency due to nonsense mutations in the epsilon subunit.

Journal

Ann Neurol 40:810-7 (1996)
DOI:10.1002/ana.410400521

Reference

PMID:9689136 (CMS5)

Authors

Ohno K, Brengman J, Tsujino A, Engel AG

Title

Human endplate acetylcholinesterase deficiency caused by mutations in the collagen-like tail subunit (ColQ) of the asymmetric enzyme.

Journal

Proc Natl Acad Sci U S A 95:9654-9 (1998)
DOI:10.1073/pnas.95.16.9654

Reference

PMID:11172068 (CMS6)

Authors

Ohno K, Tsujino A, Brengman JM, Harper CM, Bajzer Z, Udd B, Beyring R, Robb S, Kirkham FJ, Engel AG

Title

Choline acetyltransferase mutations cause myasthenic syndrome associated with episodic apnea in humans.

Journal

Proc Natl Acad Sci U S A 98:2017-22 (2001)
DOI:10.1073/pnas.98.4.2017

Reference

PMID:25192047 (CMS7A)

Authors

Herrmann DN, Horvath R, Sowden JE, Gonzalez M, Sanchez-Mejias A, Guan Z, Whittaker RG, Almodovar JL, Lane M, Bansagi B, Pyle A, Boczonadi V, Lochmuller H, Griffin H, Chinnery PF, Lloyd TE, Littleton JT, Zuchner S

Title

Synaptotagmin 2 mutations cause an autosomal-dominant form of lambert-eaton myasthenic syndrome and nonprogressive motor neuropathy.

Journal

Am J Hum Genet 95:332-9 (2014)
DOI:10.1016/j.ajhg.2014.08.007

Reference

PMID:32250532 (CMS7B)

Authors

Maselli RA, van der Linden H Jr, Ferns M

Title

Recessive congenital myasthenic syndrome caused by a homozygous mutation in SYT2 altering a highly conserved C-terminal amino acid sequence.

Journal

Am J Med Genet A 182:1744-1749 (2020)
DOI:10.1002/ajmg.a.61579

Reference

PMID:19631309 (CMS8)

Authors

Huze C, Bauche S, Richard P, Chevessier F, Goillot E, Gaudon K, Ben Ammar A, Chaboud A, Grosjean I, Lecuyer HA, Bernard V, Rouche A, Alexandri N, Kuntzer T, Fardeau M, Fournier E, Brancaccio A, Ruegg MA, Koenig J, Eymard B, Schaeffer L, Hantai D

Title

Identification of an agrin mutation that causes congenital myasthenia and affects synapse function.

Journal

Am J Hum Genet 85:155-67 (2009)
DOI:10.1016/j.ajhg.2009.06.015

Reference

PMID:15496425 (CMS9)

Authors

Chevessier F, Faraut B, Ravel-Chapuis A, Richard P, Gaudon K, Bauche S, Prioleau C, Herbst R, Goillot E, Ioos C, Azulay JP, Attarian S, Leroy JP, Fournier E, Legay C, Schaeffer L, Koenig J, Fardeau M, Eymard B, Pouget J, Hantai D

Title

MUSK, a new target for mutations causing congenital myasthenic syndrome.

Journal

Hum Mol Genet 13:3229-40 (2004)
DOI:10.1093/hmg/ddh333

Reference

PMID:16917026 (CMS10)

Authors

Beeson D, Higuchi O, Palace J, Cossins J, Spearman H, Maxwell S, Newsom-Davis J, Burke G, Fawcett P, Motomura M, Muller JS, Lochmuller H, Slater C, Vincent A, Yamanashi Y

Title

Dok-7 mutations underlie a neuromuscular junction synaptopathy.

Journal

Science 313:1975-8 (2006)
DOI:10.1126/science.1130837

Reference

PMID:11791205 (CMS11)

Authors

Ohno K, Engel AG, Shen XM, Selcen D, Brengman J, Harper CM, Tsujino A, Milone M

Title

Rapsyn mutations in humans cause endplate acetylcholine-receptor deficiency and myasthenic syndrome.

Journal

Am J Hum Genet 70:875-85 (2002)
DOI:10.1086/339465

Reference

PMID:21310273 (CMS12)

Authors

Senderek J, Muller JS, Dusl M, Strom TM, Guergueltcheva V, Diepolder I, Laval SH, Maxwell S, Cossins J, Krause S, Muelas N, Vilchez JJ, Colomer J, Mallebrera CJ, Nascimento A, Nafissi S, Kariminejad A, Nilipour Y, Bozorgmehr B, Najmabadi H, Rodolico C, Sieb JP, Steinlein OK, Schlotter B, Schoser B, Kirschner J, Herrmann R, Voit T, Oldfors A, Lindbergh C, Urtizberea A, von der Hagen M, Hubner A, Palace J, Bushby K, Straub V, Beeson D, Abicht A, Lochmuller H

Title

Hexosamine biosynthetic pathway mutations cause neuromuscular transmission defect.

Journal

Am J Hum Genet 88:162-72 (2011)
DOI:10.1016/j.ajhg.2011.01.008

Reference

PMID:22742743 (CMS13)

Authors

Belaya K, Finlayson S, Slater CR, Cossins J, Liu WW, Maxwell S, McGowan SJ, Maslau S, Twigg SR, Walls TJ, Pascual Pascual SI, Palace J, Beeson D

Title

Mutations in DPAGT1 cause a limb-girdle congenital myasthenic syndrome with tubular aggregates.

Journal

Am J Hum Genet 91:193-201 (2012)
DOI:10.1016/j.ajhg.2012.05.022

Reference

PMID:23404334 (CMS14 CMS15)

Authors

Cossins J, Belaya K, Hicks D, Salih MA, Finlayson S, Carboni N, Liu WW, Maxwell S, Zoltowska K, Farsani GT, Laval S, Seidhamed MZ, Donnelly P, Bentley D, McGowan SJ, Muller J, Palace J, Lochmuller H, Beeson D

Title

Congenital myasthenic syndromes due to mutations in ALG2 and ALG14.

Journal

Brain 136:944-56 (2013)
DOI:10.1093/brain/awt010

Reference

PMID:12766226 (CMS16)

Authors

Tsujino A, Maertens C, Ohno K, Shen XM, Fukuda T, Harper CM, Cannon SC, Engel AG

Title

Myasthenic syndrome caused by mutation of the SCN4A sodium channel.

Journal

Proc Natl Acad Sci U S A 100:7377-82 (2003)
DOI:10.1073/pnas.1230273100

Reference

PMID:24234652 (CMS17)

Authors

Ohkawara B, Cabrera-Serrano M, Nakata T, Milone M, Asai N, Ito K, Ito M, Masuda A, Ito Y, Engel AG, Ohno K

Title

LRP4 third beta-propeller domain mutations cause novel congenital myasthenia by compromising agrin-mediated MuSK signaling in a position-specific manner.

Journal

Hum Mol Genet 23:1856-68 (2014)
DOI:10.1093/hmg/ddt578

Reference

PMID:25381298 (CMS18)

Authors

Shen XM, Selcen D, Brengman J, Engel AG

Title

Mutant SNAP25B causes myasthenia, cortical hyperexcitability, ataxia, and intellectual disability.

Journal

Neurology 83:2247-55 (2014)
DOI:10.1212/WNL.0000000000001079

Reference

PMID:26626625 (CMS19)

Authors

Logan CV, Cossins J, Rodriguez Cruz PM, Parry DA, Maxwell S, Martinez-Martinez P, Riepsaame J, Abdelhamed ZA, Lake AV, Moran M, Robb S, Chow G, Sewry C, Hopkins PM, Sheridan E, Jayawant S, Palace J, Johnson CA, Beeson D

Title

Congenital Myasthenic Syndrome Type 19 Is Caused by Mutations in COL13A1, Encoding the Atypical Non-fibrillar Collagen Type XIII alpha1 Chain.

Journal

Am J Hum Genet 97:878-85 (2015)
DOI:10.1016/j.ajhg.2015.10.017

Reference

PMID:27569547 (CMS20)

Authors

Bauche S, O'Regan S, Azuma Y, Laffargue F, McMacken G, Sternberg D, Brochier G, Buon C, Bouzidi N, Topf A, Lacene E, Remerand G, Beaufrere AM, Pebrel-Richard C, Thevenon J, El Chehadeh-Djebbar S, Faivre L, Duffourd Y, Ricci F, Mongini T, Fiorillo C, Astrea G, Burloiu CM, Butoianu N, Sandu C, Servais L, Bonne G, Nelson I, Desguerre I, Nougues MC, Boeuf B, Romero N, Laporte J, Boland A, Lechner D, Deleuze JF, Fontaine B, Strochlic L, Lochmuller H, Eymard B, Mayer M, Nicole S

Title

Impaired Presynaptic High-Affinity Choline Transporter Causes a Congenital Myasthenic Syndrome with Episodic Apnea.

Journal

Am J Hum Genet 99:753-761 (2016)
DOI:10.1016/j.ajhg.2016.06.033

Reference

PMID:27590285 (CMS21)

Authors

O'Grady GL, Verschuuren C, Yuen M, Webster R, Menezes M, Fock JM, Pride N, Best HA, Benavides Damm T, Turner C, Lek M, Engel AG, North KN, Clarke NF, MacArthur DG, Kamsteeg EJ, Cooper ST

Title

Variants in SLC18A3, vesicular acetylcholine transporter, cause congenital myasthenic syndrome.

Journal

Neurology 87:1442-1448 (2016)
DOI:10.1212/WNL.0000000000003179

Reference

PMID:24610330 (CMS22)

Authors

Regal L, Shen XM, Selcen D, Verhille C, Meulemans S, Creemers JW, Engel AG

Title

PREPL deficiency with or without cystinuria causes a novel myasthenic syndrome.

Journal

Neurology 82:1254-60 (2014)
DOI:10.1212/WNL.0000000000000295

Reference

PMID:26870663 (CMS23)

Authors

Chaouch A, Porcelli V, Cox D, Edvardson S, Scarcia P, De Grassi A, Pierri CL, Cossins J, Laval SH, Griffin H, Muller JS, Evangelista T, Topf A, Abicht A, Huebner A, von der Hagen M, Bushby K, Straub V, Horvath R, Elpeleg O, Palace J, Senderek J, Beeson D, Palmieri L, Lochmuller H

Title

Mutations in the Mitochondrial Citrate Carrier SLC25A1 are Associated with Impaired Neuromuscular Transmission.

Journal

J Neuromuscul Dis 1:75-90 (2014)
DOI:10.3233/JND-140021

Reference

PMID:27259756 (CMS24)

Authors

O'Connor E, Topf A, Muller JS, Cox D, Evangelista T, Colomer J, Abicht A, Senderek J, Hasselmann O, Yaramis A, Laval SH, Lochmuller H

Title

Identification of mutations in the MYO9A gene in patients with congenital myasthenic syndrome.

Journal

Brain 139:2143-53 (2016)
DOI:10.1093/brain/aww130

Reference

PMID:28253535 (CMS25)

Authors

Salpietro V, Lin W, Delle Vedove A, Storbeck M, Liu Y, Efthymiou S, Manole A, Wiethoff S, Ye Q, Saggar A, McElreavey K, Krishnakumar SS, Pitt M, Bello OD, Rothman JE, Basel-Vanagaite L, Hubshman MW, Aharoni S, Manzur AY, Wirth B, Houlden H

Title

Homozygous mutations in VAMP1 cause a presynaptic congenital myasthenic syndrome.

Journal

Ann Neurol 81:597-603 (2017)
DOI:10.1002/ana.24905

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