congenital myasthenic syndromes

Summary

Summary: A heterogeneous group of disorders characterized by a congenital defect in neuromuscular transmission at the NEUROMUSCULAR JUNCTION. This includes presynaptic, synaptic, and postsynaptic disorders (that are not of autoimmune origin). The majority of these diseases are caused by mutations of various subunits of the nicotinic acetylcholine receptor (RECEPTORS, NICOTINIC) on the postsynaptic surface of the junction. (From Arch Neurol 1999 Feb;56(2):163-7)

Top Publications

  1. Palace J, Lashley D, Newsom Davis J, Cossins J, Maxwell S, Kennett R, et al. Clinical features of the DOK7 neuromuscular junction synaptopathy. Brain. 2007;130:1507-15 pubmed
    ..CMS due to DOK7 mutations are common within our UK cohort and is likely to be under-diagnosed; recognition of the phenotype will help clinical diagnosis, targeted genetic screening and appropriate management...
  2. Denning L, Anderson J, Davis R, Gregg J, Kuzdenyi J, Maselli R. High throughput genetic analysis of congenital myasthenic syndromes using resequencing microarrays. PLoS ONE. 2007;2:e918 pubmed
    ..We describe the performance of a custom resequencing microarray for mutational analysis of Congenital Myasthenic Syndromes (CMSs), a group of disorders in which the normal process of neuromuscular transmission is impaired.
  3. Ohno K, Engel A. Splicing abnormalities in congenital myasthenic syndromes. Acta Myol. 2005;24:50-4 pubmed
    A total of 173 mutations has been reported to date in eight genes in congenital myasthenic syndromes. Sixteen intronic and five exonic mutations in three genes affect pre-mRNA splicing...
  4. Müller J, Stucka R, Neudecker S, Zierz S, Schmidt C, Huebner A, et al. An intronic base alteration of the CHRNE gene leading to a congenital myasthenic syndrome. Neurology. 2005;65:463-5 pubmed
    ..In conclusion, RNA analysis may be necessary to reveal unexpected splicing aberrations due to intronic mutations that are not part of the consensus splice site...
  5. Wang H, Ohno K, Milone M, Brengman J, Evoli A, Batocchi A, et al. Fundamental gating mechanism of nicotinic receptor channel revealed by mutation causing a congenital myasthenic syndrome. J Gen Physiol. 2000;116:449-62 pubmed
    ..The findings further suggest that the fundamental gating mechanism of the AChR channel can be explained by a corrugated energy landscape superimposed on a steeply sloped energy well...
  6. Engel A. The therapy of congenital myasthenic syndromes. Neurotherapeutics. 2007;4:252-7 pubmed
    b>Congenital myasthenic syndromes (CMSs) are heterogeneous disorders in which the safety margin of neuromuscular transmission is compromised by one or more mechanisms...
  7. Ohno K, Engel A. Congenital myasthenic syndromes: gene mutations. Neuromuscul Disord. 2004;14:117-22 pubmed
  8. Maselli R, Dunne V, Pascual Pascual S, Bowe C, Agius M, Frank R, et al. Rapsyn mutations in myasthenic syndrome due to impaired receptor clustering. Muscle Nerve. 2003;28:293-301 pubmed
    ..Surprisingly, two N88K homozygous patients had one asymptomatic relative each who carried the same genotype, suggesting that additional genetic factors to RAPSN mutations are required for disease expression...
  9. Engel A, Ohno K, Sine S. The spectrum of congenital myasthenic syndromes. Mol Neurobiol. 2002;26:347-67 pubmed
    The past decade saw remarkable advances in defining the molecular and genetic basis of the congenital myasthenic syndromes. These advances would not have been possible without antecedent clinical observations, electrophysiologic analysis,..

More Information

Publications76

  1. Ealing J, Webster R, Brownlow S, Abdelgany A, Oosterhuis H, Muntoni F, et al. Mutations in congenital myasthenic syndromes reveal an epsilon subunit C-terminal cysteine, C470, crucial for maturation and surface expression of adult AChR. Hum Mol Genet. 2002;11:3087-96 pubmed
    Many congenital myasthenic syndromes (CMS) are associated with mutations in the genes encoding the acetylcholine receptor (AChR), an oligomeric protein with the structure alpha(2)betadelta epsilon...
  2. Anderson J, Ng J, Bowe C, McDonald C, Richman D, Wollmann R, et al. Variable phenotypes associated with mutations in DOK7. Muscle Nerve. 2008;37:448-56 pubmed
    ..Overall, our study corroborates the findings of others and provides an additional demonstration of the considerable phenotypic variability associated with CMS due to DOK7 mutations...
  3. Abicht A, Stucka R, Karcagi V, Herczegfalvi A, Horvath R, Mortier W, et al. A common mutation (epsilon1267delG) in congenital myasthenic patients of Gypsy ethnic origin. Neurology. 1999;53:1564-9 pubmed
    Mutation analysis of the acetylcholine receptor (AChR) epsilon subunit gene in patients with sporadic or autosomal recessive congenital myasthenic syndromes (CMS).
  4. Groshong J, Spencer M, Bhattacharyya B, Kudryashova E, Vohra B, Zayas R, et al. Calpain activation impairs neuromuscular transmission in a mouse model of the slow-channel myasthenic syndrome. J Clin Invest. 2007;117:2903-12 pubmed
  5. Ohno K, Tsujino A, Brengman J, Harper C, Bajzer Z, Udd B, et al. Choline acetyltransferase mutations cause myasthenic syndrome associated with episodic apnea in humans. Proc Natl Acad Sci U S A. 2001;98:2017-22 pubmed
  6. Hoffmann K, Muller J, Stricker S, Megarbane A, Rajab A, Lindner T, et al. Escobar syndrome is a prenatal myasthenia caused by disruption of the acetylcholine receptor fetal gamma subunit. Am J Hum Genet. 2006;79:303-12 pubmed
  7. Engel A, Sine S. Current understanding of congenital myasthenic syndromes. Curr Opin Pharmacol. 2005;5:308-21 pubmed
    Investigation of congenital myasthenic syndromes (CMSs) disclosed a diverse array of molecular targets at the motor endplate...
  8. Muller J, Abicht A, Christen H, Stucka R, Schara U, Mortier W, et al. A newly identified chromosomal microdeletion of the rapsyn gene causes a congenital myasthenic syndrome. Neuromuscul Disord. 2004;14:744-9 pubmed
    ..Interestingly, an Alu-mediated unequal homologous recombination may have caused the deletion. We hypothesize that numerous interspersed Alu elements may predispose the RAPSN locus for genetic rearrangements...
  9. Engel A, Ohno K, Shen X, Sine S. Congenital myasthenic syndromes: multiple molecular targets at the neuromuscular junction. Ann N Y Acad Sci. 2003;998:138-60 pubmed
    b>Congenital myasthenic syndromes (CMS) stem from defects in presynaptic, synaptic, and postsynaptic proteins. The presynaptic CMS are associated with defects that curtail the evoked release of acetylcholine (ACh) quanta or ACh resynthesis...
  10. Beeson D, Webster R, Cossins J, Lashley D, Spearman H, Maxwell S, et al. Congenital myasthenic syndromes and the formation of the neuromuscular junction. Ann N Y Acad Sci. 2008;1132:99-103 pubmed publisher
    The congenital myasthenic syndromes (CMS) are a heterogeneous group of disorders affecting neuromuscular transmission. Underlying mutations have been identified in at least 11 different genes...
  11. Huze C, Bauché S, Richard P, Chevessier F, Goillot E, Gaudon K, et al. Identification of an agrin mutation that causes congenital myasthenia and affects synapse function. Am J Hum Genet. 2009;85:155-67 pubmed publisher
    ..These results indicate that the mutation does not interfere with the ability of agrin to induce postsynaptic structures but that it dramatically perturbs the maintenance of the neuromuscular junction...
  12. Palace J, Beeson D. The congenital myasthenic syndromes. J Neuroimmunol. 2008;201-202:2-5 pubmed publisher
    The congenital myasthenic syndromes (CMS) are rare inherited disorders of neuromuscular transmission characterised by fatigable muscle weakness...
  13. Engel A, Ohno K, Sine S. Congenital myasthenic syndromes: A diverse array of molecular targets. J Neurocytol. 2003;32:1017-37 pubmed
    ..More recently, analysis of congenital myasthenic syndromes (CMS) revealed a diverse array of molecular targets and delineated their contributions to synaptic ..
  14. Tsujino A, Maertens C, Ohno K, Shen X, Fukuda T, Harper C, et al. Myasthenic syndrome caused by mutation of the SCN4A sodium channel. Proc Natl Acad Sci U S A. 2003;100:7377-82 pubmed
    ..The V1442E mutation in SCN4A defines a novel disease mechanism and a novel phenotype with myasthenic features...
  15. Nogajski J, Kiernan M, Ouvrier R, Andrews P. Congenital myasthenic syndromes. J Clin Neurosci. 2009;16:1-11 pubmed publisher
    b>Congenital myasthenic syndromes (CMS) are a heterogeneous group of uncommon, inherited disorders affecting the neuromuscular junction...
  16. Harper C. Congenital myasthenic syndromes. Semin Neurol. 2004;24:111-23 pubmed
    b>Congenital myasthenic syndromes are genetic disorders of neuromuscular transmission that should be considered in the differential diagnosis of seronegative myasthenia gravis and other neuromuscular disorders...
  17. Mihaylova V, Muller J, Vilchez J, Salih M, Kabiraj M, D Amico A, et al. Clinical and molecular genetic findings in COLQ-mutant congenital myasthenic syndromes. Brain. 2008;131:747-59 pubmed publisher
    b>Congenital myasthenic syndromes (CMS) are clinically and genetically heterogeneous inherited disorders characterized by impaired neuromuscular transmission...
  18. Engel A, Ohno K, Sine S. Congenital myasthenic syndromes: progress over the past decade. Muscle Nerve. 2003;27:4-25 pubmed
    b>Congenital myasthenic syndromes (CMS) stem from defects in presynaptic, synaptic basal lamina, and postsynaptic proteins...
  19. Kinali M, Beeson D, Pitt M, Jungbluth H, Simonds A, Aloysius A, et al. Congenital myasthenic syndromes in childhood: diagnostic and management challenges. J Neuroimmunol. 2008;201-202:6-12 pubmed publisher
    The Congenital Myasthenic Syndromes (CMS), a group of heterogeneous genetic disorders of neuromuscular transmission, are often misdiagnosed as congenital muscular dystrophy (CMD) or myopathies and present particular management problems...
  20. Beeson D, Hantai D, Lochmuller H, Engel A. 126th International Workshop: congenital myasthenic syndromes, 24-26 September 2004, Naarden, the Netherlands. Neuromuscul Disord. 2005;15:498-512 pubmed
  21. Engel A, Ohno K, Sine S. Sleuthing molecular targets for neurological diseases at the neuromuscular junction. Nat Rev Neurosci. 2003;4:339-52 pubmed
  22. Muller J, Herczegfalvi A, Vilchez J, Colomer J, Bachinski L, Mihaylova V, et al. Phenotypical spectrum of DOK7 mutations in congenital myasthenic syndromes. Brain. 2007;130:1497-506 pubmed
    ..Subsequently, we and others identified mutations in DOK7 as a cause of congenital myasthenic syndromes (CMS), providing evidence for a crucial role of Dok-7 in maintaining synaptic structure...
  23. Chevessier F, Girard E, Molgo J, Bartling S, Koenig J, Hantai D, et al. A mouse model for congenital myasthenic syndrome due to MuSK mutations reveals defects in structure and function of neuromuscular junctions. Hum Mol Genet. 2008;17:3577-95 pubmed publisher
    ..These mutant mice represent valuable models for elucidating the roles of MuSK for synapse formation, maturation and maintenance as well as for studying the pathophysiology of a CMS due to MuSK mutations...
  24. Muller J, Mihaylova V, Abicht A, Lochmuller H. Congenital myasthenic syndromes: spotlight on genetic defects of neuromuscular transmission. Expert Rev Mol Med. 2007;9:1-20 pubmed
    ..b>Congenital myasthenic syndromes (CMSs) are a genetically and phenotypically heterogeneous group of rare hereditary disorders ..
  25. Webster R, Brydson M, Croxen R, Newsom Davis J, Vincent A, Beeson D. Mutation in the AChR ion channel gate underlies a fast channel congenital myasthenic syndrome. Neurology. 2004;62:1090-6 pubmed
    Most congenital myasthenic syndromes (CMS) have postsynaptic defects from mutations within the muscle acetylcholine receptor (AChR)...
  26. Hatton C, Shelley C, Brydson M, Beeson D, Colquhoun D. Properties of the human muscle nicotinic receptor, and of the slow-channel myasthenic syndrome mutant epsilonL221F, inferred from maximum likelihood fits. J Physiol. 2003;547:729-60 pubmed
  27. Richard P, Gaudon K, Haddad H, Ammar A, Genin E, Bauche S, et al. The CHRNE 1293insG founder mutation is a frequent cause of congenital myasthenia in North Africa. Neurology. 2008;71:1967-72 pubmed publisher
    ..A single truncating mutation (epsilon1293insG) in the acetylcholine receptor epsilon subunit gene (CHRNE) was most often identified in CMS families originating from North Africa and was possibly a founder mutation...
  28. Ohno K, Engel A, Shen X, Selcen D, Brengman J, Harper C, et al. Rapsyn mutations in humans cause endplate acetylcholine-receptor deficiency and myasthenic syndrome. Am J Hum Genet. 2002;70:875-85 pubmed
    b>Congenital myasthenic syndromes (CMSs) stem from genetic defects in endplate (EP)-specific presynaptic, synaptic, and postsynaptic proteins...
  29. Ohno K, Engel A. Congenital myasthenic syndromes: genetic defects of the neuromuscular junction. Curr Neurol Neurosci Rep. 2002;2:78-88 pubmed
    b>Congenital myasthenic syndromes (CMS) stem from defects in presynaptic, synaptic, and postsynaptic proteins...
  30. Müller J, Mildner G, Müller Felber W, Schara U, Krampfl K, Petersen B, et al. Rapsyn N88K is a frequent cause of congenital myasthenic syndromes in European patients. Neurology. 2003;60:1805-10 pubmed
    Mutations in various genes of the neuromuscular junction may cause congenital myasthenic syndromes (CMS)...
  31. Engel A, Shen X, Selcen D, Sine S. Further observations in congenital myasthenic syndromes. Ann N Y Acad Sci. 2008;1132:104-13 pubmed publisher
    During the past five years many patients suffering from congenital myasthenic syndromes (CMS) have been identified worldwide and novel causative genes and mutations have been discovered...
  32. Beeson D, Higuchi O, Palace J, Cossins J, Spearman H, Maxwell S, et al. Dok-7 mutations underlie a neuromuscular junction synaptopathy. Science. 2006;313:1975-8 pubmed
    b>Congenital myasthenic syndromes (CMSs) are a group of inherited disorders of neuromuscular transmission characterized by fatigable muscle weakness...
  33. Selcen D, Milone M, Shen X, Harper C, Stans A, Wieben E, et al. Dok-7 myasthenia: phenotypic and molecular genetic studies in 16 patients. Ann Neurol. 2008;64:71-87 pubmed publisher
    ..Detailed analysis of phenotypic and molecular genetic aspects of Dok-7 myasthenia in 16 patients...
  34. Croxen R, Young C, Slater C, Haslam S, Brydson M, Vincent A, et al. End-plate gamma- and epsilon-subunit mRNA levels in AChR deficiency syndrome due to epsilon-subunit null mutations. Brain. 2001;124:1362-72 pubmed
    Acetylcholine receptor (AChR) deficiency is the most common of the congenital myasthenic syndromes (CMS)...
  35. Chevessier F, Faraut B, Ravel Chapuis A, Richard P, Gaudon K, Bauché S, et al. MUSK, a new target for mutations causing congenital myasthenic syndrome. Hum Mol Genet. 2004;13:3229-40 pubmed
    ..These results strongly suggest that the missense mutation, in the presence of a null mutation on the other allele, is responsible for the dramatic synaptic changes observed in the patient...
  36. Hantai D, Richard P, Koenig J, Eymard B. Congenital myasthenic syndromes. Curr Opin Neurol. 2004;17:539-51 pubmed
    b>Congenital myasthenic syndromes are a heterogeneous group of diseases caused by genetic defects affecting neuromuscular transmission...
  37. Engel A, Shen X, Selcen D, Sine S. What have we learned from the congenital myasthenic syndromes. J Mol Neurosci. 2010;40:143-53 pubmed publisher
    The congenital myasthenic syndromes have now been traced to an array of molecular targets at the neuromuscular junction encoded by no fewer than 11 disease genes...
  38. Yeung W, Lam C, Fung L, Hon K, Ng P. Severe congenital myasthenia gravis of the presynaptic type with choline acetyltransferase mutation in a Chinese infant with respiratory failure. Neonatology. 2009;95:183-6 pubmed publisher
    ..A high index of suspicion coupled with extended electrodiagnostic tests in clinically suspected patients will ensure the selection of appropriate genetic molecular study for confirming the diagnosis. ..
  39. Muller J, Baumeister S, Schara U, Cossins J, Krause S, von der Hagen M, et al. CHRND mutation causes a congenital myasthenic syndrome by impairing co-clustering of the acetylcholine receptor with rapsyn. Brain. 2006;129:2784-93 pubmed
    ..Introduction of the same mutation in the epsilon subunit had no effect on AChR clustering indicating a special role of the delta subunit in AChR-rapsyn interactions. ..
  40. Thompson P, Van der Werf J, Heesterbeek J, van Arendonk J. The CHRNE 470del20 mutation causing congenital myasthenic syndrome in South African Brahman cattle: prevalence, origin, and association with performance traits. J Anim Sci. 2007;85:604-9 pubmed
    ..We conclude that CMS carriers have a BW advantage at 600 d and possibly also at birth, 200 d, and 400 d. This may confer a selective advantage and tend to increase the frequency of the mutation. ..
  41. Verschuuren J, Palace J, Gilhus N. Clinical aspects of myasthenia explained. Autoimmunity. 2010;43:344-52 pubmed publisher
    ..Myasthenic phenotypes can be classified according to the basic aetiological mechanisms or divided depending on the clinical phenotype. ..
  42. Schara U, Lochmuller H. Therapeutic strategies in congenital myasthenic syndromes. Neurotherapeutics. 2008;5:542-7 pubmed publisher
    b>Congenital myasthenic syndromes (CMS) are classified in terms of the located defect: presynaptic, postsynaptic, and synaptic...
  43. Shelton G. Myasthenia gravis and congenital myasthenic syndromes in dogs and cats: A history and mini-review. Neuromuscul Disord. 2016;26:331-4 pubmed publisher
    ..b>Congenital myasthenic syndromes (CMSs) are hereditary disorders of neuromuscular transmission resulting in structural or functional ..
  44. Zhang Y, Dai Y, Han J, Chen Z, Ling L, Pu C, et al. A Novel AGRN Mutation Leads to Congenital Myasthenic Syndrome Only Affecting Limb-girdle Muscle. Chin Med J (Engl). 2017;130:2279-2282 pubmed publisher
    b>Congenital myasthenic syndromes (CMSs) are a group of clinically and genetically heterogeneous disorders caused by impaired neuromuscular transmission...
  45. Zayas R, Groshong J, Gomez C. Inositol-1,4,5-triphosphate receptors mediate activity-induced synaptic Ca2+ signals in muscle fibers and Ca2+ overload in slow-channel syndrome. Cell Calcium. 2007;41:343-52 pubmed
    ..These results suggest that a signaling system mediated by the activation of AChR, Ca2+, and IP3R is responsible for localized Ca2+ signals observed in muscle fibers and the Ca2+ overload observed in SCS. ..
  46. Maselli R, Wan J, Dunne V, Graves M, Baloh R, Wollmann R, et al. Presynaptic failure of neuromuscular transmission and synaptic remodeling in EA2. Neurology. 2003;61:1743-8 pubmed
    ..The contribution of non-P-type calcium channels to the process of neurotransmitter release in these patients likely represents a compensatory mechanism, which is insufficient to restore normal neuromuscular transmission. ..
  47. Chang T, Cossins J, Beeson D. A rare c.183_187dupCTCAC mutation of the acetylcholine receptor CHRNE gene in a South Asian female with congenital myasthenic syndrome: a case report. BMC Neurol. 2016;16:195 pubmed
    b>Congenital myasthenic syndromes (CMSs) occur as a result of genetic mutations that cause aberrations in structure and/or function of proteins involved in neuromuscular transmission...
  48. Dunne V, Maselli R. Identification of pathogenic mutations in the human rapsyn gene. J Hum Genet. 2003;48:204-7 pubmed
    ..N88K occurs within the putative leucine zipper motif potentially important for AChR clustering. These findings may explain the severe clinical involvement of compound heterozygous patients. ..
  49. Tsao C. Effective Treatment With Albuterol in DOK7 Congenital Myasthenic Syndrome in Children. Pediatr Neurol. 2016;54:85-7 pubmed publisher
    b>Congenital myasthenic syndromes consist of rare disorders resulting from mutations in genes encoding for presynaptic, synaptic, and postsynaptic proteins that are involved in the signal transmission of the neuromuscular junction...
  50. Burke G, Cossins J, Maxwell S, Robb S, Nicolle M, Vincent A, et al. Distinct phenotypes of congenital acetylcholine receptor deficiency. Neuromuscul Disord. 2004;14:356-64 pubmed
  51. Engel A, Ohno K. Congenital myasthenic syndromes. Adv Neurol. 2002;88:203-15 pubmed
  52. Cossins J, Burke G, Maxwell S, Spearman H, Man S, Kuks J, et al. Diverse molecular mechanisms involved in AChR deficiency due to rapsyn mutations. Brain. 2006;129:2773-83 pubmed
    b>Congenital myasthenic syndromes are inherited disorders of neuromuscular transmission characterized by fatigable muscle weakness...
  53. Shen X, Deymeer F, Sine S, Engel A. Slow-channel mutation in acetylcholine receptor alphaM4 domain and its efficient knockdown. Ann Neurol. 2006;60:128-36 pubmed
    ..To identify the genetic basis of a slow-channel myasthenic syndrome, characterize functional properties of the mutant receptor, and selectively silence the mutant allele...
  54. Zafeiriou D, Pitt M, de Sousa C. Clinical and neurophysiological characteristics of congenital myasthenic syndromes presenting in early infancy. Brain Dev. 2004;26:47-52 pubmed
    The congenital myasthenic syndromes (CMS) constitute a group of genetic disorders, which affect neuromuscular transmission, presenting usually within the first years of life and with a clinical spectrum ranging from mild muscle weakness ..
  55. Koenigsberger M, Pascual J. [Neonatal myasthenic syndromes]. Rev Neurol. 2002;34:47-51 pubmed
    ..The deficit in function of the NMJ is presynaptic in 3 instances, at the junctional gap in 1, and postsynaptic in at least 3 other syndromes...
  56. Srour M, Bolduc V, Guergueltcheva V, Lochmuller H, Gendron D, Shevell M, et al. DOK7 mutations presenting as a proximal myopathy in French Canadians. Neuromuscul Disord. 2010;20:453-7 pubmed publisher
    ..DOK7 mutations should be considered in patients with early-onset myopathy, even in the absence of symptoms suggesting a possible myasthenia...
  57. Harper C, Fukodome T, Engel A. Treatment of slow-channel congenital myasthenic syndrome with fluoxetine. Neurology. 2003;60:1710-3 pubmed
    ..Both patients showed marked subjective and objective improvement by quantitative muscle strength testing and electromyography...
  58. Marouf W, Sieb J. [Myasthenia gravis and myasthenic syndromes]. Z Rheumatol. 2009;68:465-70 pubmed publisher
    ..The abnormality in LEMS is a presynaptic failure to acetylcholine release caused by antibodies to voltage-gated calcium channels. More than half of LEMS patients have small-cell lung cancer...
  59. Maselli R, Ng J, Anderson J, Cagney O, Arredondo J, Williams C, et al. Mutations in LAMB2 causing a severe form of synaptic congenital myasthenic syndrome. J Med Genet. 2009;46:203-8 pubmed publisher
    ..We describe a severe form of congenital myasthenic syndrome (CMS) associated with congenital nephrosis and ocular malformations caused by two truncating mutations in the gene encoding the laminin beta2 subunit (LAMB2)...
  60. Andreux F, Hantai D, Eymard B. [Congenital myasthenic syndromes: phenotypic expression and pathophysiological characterisation]. Rev Neurol (Paris). 2004;160:163-76 pubmed
    b>Congenital Myasthenic Syndromes (CMS) are a heterogeneous group of diseases caused by genetic defects affecting neuromuscular transmission...
  61. Eymard B, Ioos C, Barois A, Estournet B, Mayer M, Fournier E, et al. [Congenital myasthenic syndromes due to mutations in the rapsyn gene]. Rev Neurol (Paris). 2004;160:S78-84 pubmed
    b>Congenital myasthenic syndromes (CMS) are genetic diseases characterized by dysfunctional neuromuscular transmission and usually start during the neonatal period...
  62. Ohno K, Tsujino A, Shen X, Milone M, Engel A. Spectrum of splicing errors caused by CHRNE mutations affecting introns and intron/exon boundaries. J Med Genet. 2005;42:e53 pubmed
    ..in CHRNE, the gene encoding the muscle nicotinic acetylcholine receptor epsilon subunit, cause congenital myasthenic syndromes. Only three of the eight intronic splice site mutations of CHRNE reported to date have had their ..
  63. Ben Youssef Turki I, Kraoua I, Gargouri A, Akopova Larbi R, Gouider R, Gouider Khouja N. [Slow channel syndrome: clinical and neurophysiological aspects]. Tunis Med. 2008;86:202-4 pubmed
  64. Mallory L, Shaw J, Burgess S, Estrella E, Nurko S, Burpee T, et al. Congenital myasthenic syndrome with episodic apnea. Pediatr Neurol. 2009;41:42-5 pubmed publisher
    ..Pyridostigmine is the primary therapy for choline acetyltransferase deficiency, but the efficacy of midazolam during this patient's episodes of apnea is interesting, and warrants further study...
  65. Müller J, Petrova S, Kiefer R, Stucka R, Konig C, Baumeister S, et al. Synaptic congenital myasthenic syndrome in three patients due to a novel missense mutation (T441A) of the COLQ gene. Neuropediatrics. 2004;35:183-9 pubmed
    b>Congenital myasthenic syndromes (CMS) with deficiency of endplate acetylcholinesterase (AChE) are caused by mutations in the synapse specific collagenic tail subunit gene (COLQ) of AChE...
  66. Fidzianska A, Ryniewicz B, Shen X, Engel A. IBM-type inclusions in a patient with slow-channel syndrome caused by a mutation in the AChR epsilon subunit. Neuromuscul Disord. 2005;15:753-9 pubmed
    ..Molecular genetic studies revealed a novel valine to phenylalanine mutation (epsilonV259F) in the M2 domain of the acetylcholine receptor. Coexistence of the slow-channel syndrome with a feature of IBM has not been observed before...
  67. Sieb J, Kraner S, Rauch M, Steinlein O. Immature end-plates and utrophin deficiency in congenital myasthenic syndrome caused by epsilon-AChR subunit truncating mutations. Hum Genet. 2000;107:160-4 pubmed
    b>Congenital myasthenic syndromes (CMS) are inborn disorders due to presynaptic, synaptic, or postsynaptic defects of neuromuscular transmission...