myotonia

Summary

Summary: Prolonged failure of muscle relaxation after contraction. This may occur after voluntary contractions, muscle percussion, or electrical stimulation of the muscle. Myotonia is a characteristic feature of MYOTONIC DISORDERS.

Top Publications

  1. Gurnett C, Kahl S, Anderson R, Campbell K. Absence of the skeletal muscle sarcolemma chloride channel ClC-1 in myotonic mice. J Biol Chem. 1995;270:9035-8 pubmed
    ..Mutations in the ClC-1 gene are responsible for both human autosomal recessive generalized myotonia and autosomal dominant myotonia congenita...
  2. Bissay V, Keymolen K, Lissens W, Laureys G, Schmedding E, de Keyser J. Late onset painful cold-aggravated myotonia: three families with SCN4A L1436P mutation. Neuromuscul Disord. 2011;21:590-3 pubmed publisher
    We describe three Belgian families with a L1436P mutation in the SCN4A gene, causing a sodium channel myotonia with an atypical clinical presentation, characterized by late onset painful cold-aggravated myotonia...
  3. Yoshinaga H, Sakoda S, Good J, Takahashi M, Kubota T, Arikawa Hirasawa E, et al. A novel mutation in SCN4A causes severe myotonia and school-age-onset paralytic episodes. J Neurol Sci. 2012;315:15-9 pubmed publisher
    ..channel (SCN4A) are responsible for hyperkalemic periodic paralysis, paramyotonia congenita and sodium channel myotonia. These disorders are classified based on their cardinal symptoms, myotonia and/or paralysis...
  4. Wu F, Gordon E, Hoffman E, Cannon S. A C-terminal skeletal muscle sodium channel mutation associated with myotonia disrupts fast inactivation. J Physiol. 2005;565:371-80 pubmed
    ..A patient with cold-aggravated myotonia did not harbour any of the common SCN4A mutations...
  5. Macias M, Teijido O, Zifarelli G, Martin P, Ramirez Espain X, Zorzano A, et al. Myotonia-related mutations in the distal C-terminus of ClC-1 and ClC-0 chloride channels affect the structure of a poly-proline helix. Biochem J. 2007;403:79-87 pubmed
    b>Myotonia is a state of hyperexcitability of skeletal-muscle fibres. Mutations in the ClC-1 Cl- channel cause recessive and dominant forms of this disease...
  6. Kwiecinski H, Ryniewicz B, Ostrzycki A. Treatment of myotonia with antiarrhythmic drugs. Acta Neurol Scand. 1992;86:371-5 pubmed
    ..The severity of myotonia was assessed by clinical and electromyographic criteria at the end of each treatment phase lasting four weeks...
  7. Kurihara T, Kishi M, Saito N, Komoto M, Hidaka T, Kinoshita M. Electrical myotonia and cataract in X-linked muscular dystrophy (mdx) mouse. J Neurol Sci. 1990;99:83-92 pubmed
    ..recordings from the mdx mouse hemidiaphragm preparations revealed low resting membrane potentials and electrical myotonia which occurred at the time of microelectrode insertion and withdrawal...
  8. van Lunteren E, Spiegler S, Moyer M. Fatigue-inducing stimulation resolves myotonia in a drug-induced model. BMC Physiol. 2011;11:5 pubmed publisher
    Slowed muscle relaxation is the contractile hallmark of myotonia congenita, a disease caused by genetic CLC-1 chloride channel deficiency, which improves with antecedent brief contractions ("warm-up phenomenon")...
  9. Stunnenberg B, Ginjaar H, Trip J, Faber C, van Engelen B, Drost G. Isolated eyelid closure myotonia in two families with sodium channel myotonia. Neurogenetics. 2010;11:257-60 pubmed publisher
    ..myotonic syndromes (NDMs), reflect a heterogeneous group of clinical phenotypes accompanied by a generalized myotonia. Because of recent availability of diagnostic genetic testing in NDM, there is a need for identification of clear ..

More Information

Publications62

  1. Fournier E, Viala K, Gervais H, Sternberg D, Arzel Hézode M, Laforet P, et al. Cold extends electromyography distinction between ion channel mutations causing myotonia. Ann Neurol. 2006;60:356-65 pubmed
    ..Nondystrophic forms are caused by mutations in genes coding for the muscle chloride or sodium channel. Myotonia is either relieved or worsened by repeated exercise and can merge into flaccid weakness during exposure to cold, ..
  2. Kanadia R, Shin J, Yuan Y, Beattie S, Wheeler T, Thornton C, et al. Reversal of RNA missplicing and myotonia after muscleblind overexpression in a mouse poly(CUG) model for myotonic dystrophy. Proc Natl Acad Sci U S A. 2006;103:11748-53 pubmed
    ..muscle with a recombinant adeno-associated viral vector rescues disease-associated muscle hyperexcitability, or myotonia, in the HSA(LR) poly(CUG) mouse model for DM...
  3. van Lunteren E, Moyer M, Pollarine J. Genetic CLC-1 chloride channel deficiency modifies diaphragm muscle isometric contractile properties. Respir Physiol Neurobiol. 2007;155:220-6 pubmed
    Genetic deficiency of the muscle chloride channel CLC-1 leads to myotonia congenita in humans as well as myotonia in mice and goats...
  4. Vite C. Myotonia and disorders of altered muscle cell membrane excitability. Vet Clin North Am Small Anim Pract. 2002;32:169-87, vii pubmed
    ..Hyperexcitability of the sarcolemma results in myotonia, and hypoexcitability results in paresis or paralysis...
  5. Desaphy J, De Luca A, Didonna M, George A, Camerino Conte D, Luca A. Different flecainide sensitivity of hNav1.4 channels and myotonic mutants explained by state-dependent block. J Physiol. 2004;554:321-34 pubmed
    Flecainide, a class IC antiarrhythmic, was shown to improve myotonia caused by sodium channel mutations in situations where the class IB antiarrhythmic drug mexiletine was less efficient...
  6. Beck C, Fahlke C, George A. Molecular basis for decreased muscle chloride conductance in the myotonic goat. Proc Natl Acad Sci U S A. 1996;93:11248-52 pubmed
    Certain forms of myotonia, a condition characterized by delayed relaxation of muscle secondary to sarcolemmal hyperexcitability, are caused by diminished chloride conductance in the muscle cell membrane...
  7. Meyer Kleine C, Steinmeyer K, Ricker K, Jentsch T, Koch M. Spectrum of mutations in the major human skeletal muscle chloride channel gene (CLCN1) leading to myotonia. Am J Hum Genet. 1995;57:1325-34 pubmed
    Autosomal dominant myotonia congenita and autosomal recessive generalized myotonia (GM) are genetic disorders characterized by the symptom of myotonia, which is based on an electrical instability of the muscle fiber membrane...
  8. Koch M, Ricker K, Otto M, Wolf F, Zoll B, Lorenz C, et al. Evidence for genetic homogeneity in autosomal recessive generalised myotonia (Becker). J Med Genet. 1993;30:914-7 pubmed
    Generalised myotonia Becker (GM) is an autosomal recessively inherited muscle disorder. Affected subjects exhibit myotonic muscle stiffness in all skeletal muscles with marked hypertrophy in the legs...
  9. Burgunder J, Huifang S, Beguin P, Baur R, Eng C, Seet R, et al. Novel chloride channel mutations leading to mild myotonia among Chinese. Neuromuscul Disord. 2008;18:633-40 pubmed publisher
    We describe two Chinese families with a mild form of the myotonia congenita due to novel chloride channel (ClCN1) mutations. In one case, heterozygous I553F and H555N mutations were found...
  10. Lehmann Horn F, Mailänder V, Heine R, George A. Myotonia levior is a chloride channel disorder. Hum Mol Genet. 1995;4:1397-402 pubmed
    ..Dominant myotonia congenita (Thomsen's disease) is linked to CLCN1, the gene encoding the major muscle chloride channel, localized ..
  11. Lehmann Horn F, Jurkat Rott K, Rudel R. Diagnostics and therapy of muscle channelopathies--Guidelines of the Ulm Muscle Centre. Acta Myol. 2008;27:98-113 pubmed
    ..state-of-the-art diagnostics and therapies for the two types of myotonic dystrophies, for recessive and dominant myotonia congenita, for the sodium channel myotonias, for the primary dyskalemic periodic paralyses, for central core ..
  12. Füchtbauer E, Reininghaus J, Jockusch H. Developmental control of the excitability of muscle: transplantation experiments on a myotonic mouse mutant. Proc Natl Acad Sci U S A. 1988;85:3880-4 pubmed
    Developmental aspects of an animal model of myotonia, the mouse mutant called "arrested development of righting response" (ADR phenotype), were studied...
  13. Rossignol E, Mathieu J, Thiffault I, Tetreault M, Dicaire M, Chrestian N, et al. A novel founder SCN4A mutation causes painful cold-induced myotonia in French-Canadians. Neurology. 2007;69:1937-41 pubmed
    b>Myotonia is observed in classic congenital myotonia caused by CLCN1 mutations and in sodium-channel myotonia (SCM) due to SCN4A mutations.
  14. Hayward L, Kim J, Lee M, Zhou H, Kim J, Misra K, et al. Targeted mutation of mouse skeletal muscle sodium channel produces myotonia and potassium-sensitive weakness. J Clin Invest. 2008;118:1437-49 pubmed publisher
    Hyperkalemic periodic paralysis (HyperKPP) produces myotonia and attacks of muscle weakness triggered by rest after exercise or by K+ ingestion...
  15. Dupre N, Chrestian N, Bouchard J, Rossignol E, Brunet D, Sternberg D, et al. Clinical, electrophysiologic, and genetic study of non-dystrophic myotonia in French-Canadians. Neuromuscul Disord. 2009;19:330-4 pubmed publisher
    Thirty-three French-Canadian families with non-dystrophic myotonia were identified. Fifty subjects were recruited and submitted to a complete clinical, electrophysiologic and genetic evaluation...
  16. Petitprez S, Tiab L, Chen L, Kappeler L, Rösler K, Schorderet D, et al. A novel dominant mutation of the Nav1.4 alpha-subunit domain I leading to sodium channel myotonia. Neurology. 2008;71:1669-75 pubmed publisher
    Mutations in SCN4A may lead to myotonia.
  17. Groome J, Fujimoto E, Ruben P. K-aggravated myotonia mutations at residue G1306 differentially alter deactivation gating of human skeletal muscle sodium channels. Cell Mol Neurobiol. 2005;25:1075-92 pubmed
    ..4) and potassium-aggravated myotonia (PAM) mutations G1306A, G1306E, and G1306V...
  18. Steinmeyer K, Klocke R, Ortland C, Gronemeier M, Jockusch H, Grunder S, et al. Inactivation of muscle chloride channel by transposon insertion in myotonic mice. Nature. 1991;354:304-8 pubmed
    b>MYOTONIA (stiffness and impaired relaxation of skeletal muscle) is a symptom of several diseases caused by repetitive firing of action potentials in muscle membranes...
  19. Wischmeyer E, Nolte E, Klocke R, Jockusch H, Brinkmeier H. Development of electrical myotonia in the ADR mouse: role of chloride conductance in myotubes and neonatal animals. Neuromuscul Disord. 1993;3:267-74 pubmed
    ..of the autosomal mutation adr, "arrested development of righting response", leads to the symptoms of myotonia. The adr mutation is caused by an insertion of a retroposon into a gene for a chloride channel (adr = Clc-1) that ..
  20. Statland J, Bundy B, Wang Y, Rayan D, Trivedi J, Sansone V, et al. Mexiletine for symptoms and signs of myotonia in nondystrophic myotonia: a randomized controlled trial. JAMA. 2012;308:1357-65 pubmed publisher
    ..Mexiletine-induced sodium channel blockade reduced myotonia in small studies; however, as is common in rare diseases, larger studies of safety and efficacy have not ..
  21. Montagna P, Liguori R, Monari L, Strong P, Riva R, Di Stasi V, et al. Equine muscular dystrophy with myotonia. Clin Neurophysiol. 2001;112:294-9 pubmed
    To describe a case of equine muscular dystrophy with myotonia.
  22. Kokunai Y, Goto K, Kubota T, Fukuoka T, Sakoda S, Ibi T, et al. A sodium channel myotonia due to a novel SCN4A mutation accompanied by acquired autoimmune myasthenia gravis. Neurosci Lett. 2012;519:67-72 pubmed publisher
    Mutations of the voltage gated sodium channel gene (SCN4A) are responsible for non-dystrophic myotonia including hyperkalemic periodic paralysis, paramyotonia congenita, and sodium channel myotonia, as well as congenital myasthenic ..
  23. Heimann P, Augustin M, Wieneke S, Heising S, Jockusch H. Mutual interference of myotonia and muscular dystrophy in the mouse: a study on ADR-MDX double mutants. Neuromuscul Disord. 1998;8:551-60 pubmed
    For Duchenne muscular dystrophy (DMD, dystrophin deficiency) and Thomsen/Becker myotonia (muscular chloride channel deficiency) genetically homologous mouse models are available, the dystrophin-deficient MDX mouse and the myotonic ADR ..
  24. Reininghaus J, Füchtbauer E, Bertram K, Jockusch H. The myotonic mouse mutant ADR: physiological and histochemical properties of muscle. Muscle Nerve. 1988;11:433-9 pubmed
    ..These physiological data suggest that ADR is a myotonia. With a few exceptions, limb and trunk muscles of ADR animals showed a uniform oxidative phenotype with a lack of ..
  25. Mazón M, Barros F, de la Pena P, Quesada J, Escudero A, Cobo A, et al. Screening for mutations in Spanish families with myotonia. Functional analysis of novel mutations in CLCN1 gene. Neuromuscul Disord. 2012;22:231-43 pubmed publisher
    b>Myotonia congenita is an inherited muscle disorder caused by mutations in the CLCN1 gene, a voltage-gated chloride channel of skeletal muscle...
  26. Finnigan D, Hanna W, Poma R, Bendall A. A novel mutation of the CLCN1 gene associated with myotonia hereditaria in an Australian cattle dog. J Vet Intern Med. 2007;21:458-63 pubmed
    Heritable myotonia is a genetic muscle disorder characterized by slow relaxation of skeletal muscles. The main clinical signs are skeletal muscle stiffness, especially after vigorous contraction, and muscle hypertrophy...
  27. Bryant S, Morales Aguilera A. Chloride conductance in normal and myotonic muscle fibres and the action of monocarboxylic aromatic acids. J Physiol. 1971;219:367-83 pubmed
    ..It is concluded that these compounds block chloride conductance.4. The carboxylic acids produced myotonia in normal fibres similar to that in untreated myotonic fibres.5...
  28. Orrell R, Jurkat Rott K, Lehmann Horn F, Lane R. Familial cramp due to potassium-aggravated myotonia. J Neurol Neurosurg Psychiatry. 1998;65:569-72 pubmed
    ..the skeletal muscle sodium channel gene in both patients, consistent with the diagnosis of potassium-aggravated myotonia. The phenotype in this family is much milder than that previously described in another family with a mutation at ..
  29. Matthews E, Fialho D, Tan S, Venance S, Cannon S, Sternberg D, et al. The non-dystrophic myotonias: molecular pathogenesis, diagnosis and treatment. Brain. 2010;133:9-22 pubmed publisher
    ..Many distinct clinical phenotypes are now recognized and range in severity from severe neonatal myotonia with respiratory compromise through to milder late-onset myotonic muscle stiffness...
  30. Mehrke G, Brinkmeier H, Jockusch H. The myotonic mouse mutant ADR: electrophysiology of the muscle fiber. Muscle Nerve. 1988;11:440-6 pubmed
    ..4 times longer. This finding indicated a drastic reduction of chloride conductance of the ADR muscle membrane. We conclude that ADR is a myotonia, related in its etiology to hereditary myotonias of man.
  31. Wu F, Takahashi M, Pegoraro E, Angelini C, Colleselli P, Cannon S, et al. A new mutation in a family with cold-aggravated myotonia disrupts Na(+) channel inactivation. Neurology. 2001;56:878-84 pubmed
    To identify the molecular and physiologic abnormality in familial myotonia with cold sensitivity, hypertrophy, and no weakness.
  32. Ryan A, Rüdel R, Kuchenbecker M, Fahlke C. A novel alteration of muscle chloride channel gating in myotonia levior. J Physiol. 2002;545:345-54 pubmed
    Mutations in the voltage-dependent skeletal muscle chloride channel, ClC-1, result in dominant or recessive myotonia congenita. The Q552R mutation causes a variant of dominant myotonia with a milder phenotype, myotonia levior...
  33. Statland J, Wang Y, Richesson R, Bundy B, Herbelin L, Gomes J, et al. An interactive voice response diary for patients with non-dystrophic myotonia. Muscle Nerve. 2011;44:30-5 pubmed publisher
    Non-dystrophic myotonia (NDM) is caused by mutations in muscle chloride and sodium channels. Currently, there is no standardized instrument for documenting symptom frequency and severity in NDM.
  34. Trivedi J, Bundy B, Statland J, Salajegheh M, Rayan D, Venance S, et al. Non-dystrophic myotonia: prospective study of objective and patient reported outcomes. Brain. 2013;136:2189-200 pubmed publisher
    ..Few prospective studies have evaluated the sensitivity of symptoms and signs of myotonia in a large cohort of patients...
  35. Kubota T, Roca X, Kimura T, Kokunai Y, Nishino I, Sakoda S, et al. A mutation in a rare type of intron in a sodium-channel gene results in aberrant splicing and causes myotonia. Hum Mutat. 2011;32:773-82 pubmed publisher
    Many mutations in the skeletal-muscle sodium-channel gene SCN4A have been associated with myotonia and/or periodic paralysis, but so far all of these mutations are located in exons...
  36. Heine R, Pika U, Lehmann Horn F. A novel SCN4A mutation causing myotonia aggravated by cold and potassium. Hum Mol Genet. 1993;2:1349-53 pubmed
    The single strand conformation polymorphism (SSCP) technique was used to screen genomic DNA of a family with myotonia aggravated by cold, potassium loading and suxamethonium, but without muscle weakness...
  37. Desaphy J, Costanza T, Carbonara R, Conte Camerino D. In vivo evaluation of antimyotonic efficacy of ?-adrenergic drugs in a rat model of myotonia. Neuropharmacology. 2013;65:21-7 pubmed publisher
    ..We now developed a pharmacological rat model of myotonia congenita to perform in vivo preclinical test of antimyotonic drugs. Myotonia was induced by i.p...
  38. Aoike F, Takahashi M, Sakoda S. Class Ic antiarrhythmics block human skeletal muscle Na channel during myotonia-like stimulation. Eur J Pharmacol. 2006;532:24-31 pubmed
    Flecainide, a class Ic antiarrhythmic drug, has been anecdotally reported to improve myotonia, but little is known about its kinetics on human skeletal muscle sodium channels applicable in vivo...
  39. Pusch M. Myotonia caused by mutations in the muscle chloride channel gene CLCN1. Hum Mutat. 2002;19:423-34 pubmed
    Pure non-syndromic, non-dystrophic myotonia in humans is caused by mutations in the genes coding for the skeletal muscle sodium channel (SCN5A) or the skeletal muscle chloride channel (CLCN1) with similar phenotypes...
  40. Lerche H, Heine R, Pika U, George A, Mitrovic N, Browatzki M, et al. Human sodium channel myotonia: slowed channel inactivation due to substitutions for a glycine within the III-IV linker. J Physiol. 1993;470:13-22 pubmed
    1. Three families with a form of myotonia (muscle stiffness due to membrane hyperexcitability) clinically distinct from previously classified myotonias were examined. The severity of the disease greatly differed among the families. 2...
  41. Grunnet M, Jespersen T, Colding Jørgensen E, Schwartz M, Klaerke D, Vissing J, et al. Characterization of two new dominant ClC-1 channel mutations associated with myotonia. Muscle Nerve. 2003;28:722-32 pubmed
    ..More than 60 CLCN1 mutations have been associated with myotonia congenita...
  42. Zimon M, Baets J, Almeida Souza L, De Vriendt E, Nikodinovic J, Parman Y, et al. Loss-of-function mutations in HINT1 cause axonal neuropathy with neuromyotonia. Nat Genet. 2012;44:1080-3 pubmed publisher
    ..Our study provides evidence that loss of functional HINT1 protein results in a distinct phenotype of autosomal recessive axonal neuropathy with neuromyotonia...
  43. Vindas Smith R, Fiore M, Vásquez M, Cuenca P, Del Valle G, Lagostena L, et al. Identification and Functional Characterization of CLCN1 Mutations Found in Nondystrophic Myotonia Patients. Hum Mutat. 2016;37:74-83 pubmed publisher
    Mutations in the gene coding for the skeletal muscle Cl(-) channel (CLCN1) lead to dominant or recessive myotonia. Here, we identified and characterized CLCN1 mutations in Costa Rican patients, who had been clinically diagnosed with ..
  44. Dabby R, Sadeh M, Herman O, Leibou L, Kremer E, Mordechai S, et al. Clinical, electrophysiologic and pathologic findings in 10 patients with myotonic dystrophy 2. Isr Med Assoc J. 2011;13:745-7 pubmed
    ..Myotonic dystrophy type 2 (DM2) is an autosomal dominant, multisystem disorder caused by a CCTG tetranucleotide repeat expansion located in intron 1 of the zinc finger protein 9 gene (ZNF9 gene) on chromosome 3q 21.3...
  45. Torbergsen T, Hødnebø A, Brautaset N, Løseth S, Stalberg E. A rare form of painful nondystrophic myotonia. Clin Neurophysiol. 2003;114:2347-54 pubmed
    In this paper we report a painful nondystrophic myotonia which has not been previously described. Pain is a rare symptom in myotonia. We report a myotonic disorder in a 34-year-old woman and her 14-year-old daughter...
  46. Lewin J, Bishop Leone J, Forman A, Diaz E. Further experience with Botox injection for tracheoesophageal speech failure. Head Neck. 2001;23:456-60 pubmed
    ..Botox injection relieves hypertonicity, but there are little objective data regarding outcomes, duration of effect, and reinjection rates...
  47. Cannon S. Spectrum of sodium channel disturbances in the nondystrophic myotonias and periodic paralyses. Kidney Int. 2000;57:772-9 pubmed
    Several heritable forms of myotonia and periodic paralysis are caused by missense mutations in the voltage-gated sodium channel of skeletal muscle...
  48. Moran O, Nizzari M, Conti F. Inactivation defects produced by a myopathic II-S6 mutation of the muscle sodium channel. Biochem Biophys Res Commun. 1998;246:792-6 pubmed
    ..The changes on the inactivation properties of the mutant channel may be related with the muscle fibre hyperexcitability observed patients affected by PAM...
  49. Mrabet H, Masmoudi S, Mrabet A. [Myotonia and hypothyroidism]. Rev Neurol (Paris). 2007;163:837-9 pubmed
    Hypothyroidism is frequently associated with different neuromuscular disorders. However myotonia is rarely a revealing feature.
  50. Nagado T, Arimura K, Sonoda Y, Kurono A, Horikiri Y, Kameyama A, et al. Potassium current suppression in patients with peripheral nerve hyperexcitability. Brain. 1999;122 ( Pt 11):2057-66 pubmed
  51. Toyka K, Zielasek J, Ricker K, Adlkofer K, Suter U. Hereditary neuromyotonia: a mouse model associated with deficiency or increased gene dosage of the PMP22 gene. J Neurol Neurosurg Psychiatry. 1997;63:812-3 pubmed
  52. Goblet C, Whalen R. Modifications of gene expression in myotonic murine skeletal muscle are associated with abnormal expression of myogenic regulatory factors. Dev Biol. 1995;170:262-73 pubmed
    ..These observations suggest that specific myogenic factors may be linked to the expression of individual MyHC genes and that abnormal expression of some of the factors may be associated with myotonic muscle pathology...
  53. Lehmann Horn F, Iaizzo P, Franke C, Hatt H, Spaans F. Schwartz-Jampel syndrome: II. Na+ channel defect causes myotonia. Muscle Nerve. 1990;13:528-35 pubmed
    ..These abnormal openings occurred even after the surface membrane repolarized. We hypothesize that these altered membrane conductances are responsible for the hyperexcitability and the associated slowed relaxation...