-
Advances in Genetics 2008Myotonia is a symptom of many different acquired and genetic muscular conditions that impair the relaxation phase of muscular contraction. Myotonia congenita is a... (Review)
Review
Myotonia is a symptom of many different acquired and genetic muscular conditions that impair the relaxation phase of muscular contraction. Myotonia congenita is a specific inherited disorder of muscle membrane hyperexcitability caused by reduced sarcolemmal chloride conductance due to mutations in CLCN1, the gene coding for the main skeletal muscle chloride channel ClC-1. The disorder may be transmitted as either an autosomal-dominant or recessive trait with close to 130 currently known mutations. Although this is a rare disorder, elucidation of the pathophysiology underlying myotonia congenita established the importance of sarcolemmal chloride conductance in the control of muscle excitability and demonstrated the first example of human disease associated with the ClC family of chloride transporting proteins.
Topics: Animals; Chloride Channels; Disease Models, Animal; Humans; Mutation; Myotonia Congenita
PubMed: 19185184
DOI: 10.1016/S0065-2660(08)01002-X -
Seminars in Neurology Sep 1991There are two types of MC, autosomal dominant and autosomal recessive (also called recessive generalized myotonia), both with the predominant clinical feature of diffuse... (Review)
Review
There are two types of MC, autosomal dominant and autosomal recessive (also called recessive generalized myotonia), both with the predominant clinical feature of diffuse myotonia. Recessive MC patients have more weakness than patients with dominant MC. MC patients of both types have a normal life span. Ongoing genetic studies have not as yet identified any chromosomal linkage. Electrophysiologically and pathophysiologically, there is no difference between these two types. The major pathophysiologic abnormality is decreased membrane chloride conductance. Treatment of myotonia is not always necessary, but when it is, the most effective medications are those that stabilize the muscle membrane. Phenytoin is frequently the first choice because it has more benign side effect profile than other drugs and a reasonable response rate.
Topics: Diagnosis, Differential; Electrophysiology; Humans; Muscular Dystrophies; Myotonia Congenita
PubMed: 1947487
DOI: 10.1055/s-2008-1041228 -
Channels (Austin, Tex.) Dec 2022Myotonia congenita (MC) is a rare genetic disease caused by mutations in the skeletal muscle chloride channel gene (), encoding the voltage-gated chloride channel ClC-1... (Review)
Review
Myotonia congenita (MC) is a rare genetic disease caused by mutations in the skeletal muscle chloride channel gene (), encoding the voltage-gated chloride channel ClC-1 in skeletal muscle. Our study reported the clinical and molecular characteristics of six patients with MC and systematically review the literature on Chinese people. We retrospectively analyzed demographics, clinical features, family history, creatine kinase (CK), electromyography (EMG), treatment, and genotype data of our patients and reviewed the clinical data and mutations in literature. The median ages at examination and onset were 26.5 years (range 11-50 years) and 6.5 years (range 1.5-11 years), respectively, in our patients, and 21 years (range 3.5-65 years, n = 45) and 9 years (range 0.5-26 years, n = 50), respectively, in literature. Similar to previous reports, myotonia involved limb, lids, masticatory, and trunk muscles to varying degrees. Warm-up phenomenon (5/6), percussion myotonia (3/5), and grip myotonia (6/6) were common. Menstruation triggered myotonia in females, not observed in Chinese patients before. The proportion of abnormal CK levels (4/5) was higher than data from literature. Electromyography performed in six patients revealed myotonic changes (100%). Five novel mutations, including a splicing mutation (c.853 + 4A>G), a deletion mutation (c.2010_2014del), and three missense mutations (c.2527C>T, c.1727C>T, c.2017 G > C), were identified. The c.892 G > A (p.A298T) mutation was the most frequent mutation in the Chinese population. Our study expanded the clinical and genetic spectrum of patients with MC in the China. The MC phenotype in Chinese people is not different from that found in the West, while the genotype is different.
Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Chloride Channels; Female; Humans; Infant; Middle Aged; Mutation; Myotonia; Myotonia Congenita; Retrospective Studies; Young Adult
PubMed: 35170402
DOI: 10.1080/19336950.2022.2041292 -
The American Journal of the Medical... Jun 2022
Topics: Humans; Mutation; Myotonia Congenita
PubMed: 33531161
DOI: 10.1016/j.amjms.2020.11.010 -
Muscle & Nerve Jul 2005Myotonia congenita is a hereditary chloride channel disorder characterized by delayed relaxation of skeletal muscle (myotonia). It is caused by mutations in the skeletal... (Review)
Review
Myotonia congenita is a hereditary chloride channel disorder characterized by delayed relaxation of skeletal muscle (myotonia). It is caused by mutations in the skeletal muscle chloride channel gene CLCN1 on chromosome 7. The phenotypic spectrum of myotonia congenita ranges from mild myotonia disclosed only by clinical examination to severe and disabling myotonia with transient weakness and myopathy. The most severe phenotypes are seen in patients with two mutated alleles. Heterozygotes are often asymptomatic but for some mutations heterozygosity is sufficient to cause pronounced myotonia, although without weakness and myopathy. Thus, the phenotype depends on the mutation type to some extent, but this does not explain the fact that severity varies greatly between heterozygous family members and may even vary with time in the individual patient. In this review, existing knowledge about phenotypic variability is summarized, and the possible contributing factors are discussed.
Topics: Chloride Channels; Genetic Variation; Humans; Myotonia Congenita; Pedigree; Phenotype
PubMed: 15786415
DOI: 10.1002/mus.20295 -
No To Shinkei = Brain and Nerve Dec 1997
Review
Topics: Animals; Chloride Channels; Electromyography; Humans; Muscle Proteins; Muscle, Skeletal; Myotonia Congenita
PubMed: 9453038
DOI: No ID Found -
Journal of Genetics Sep 2019Myotonia congenita (MC) is a Mendelian inherited genetic disease caused by the mutations in the gene, encoding the main skeletal muscle ion chloride channel (ClC-1)....
Myotonia congenita (MC) is a Mendelian inherited genetic disease caused by the mutations in the gene, encoding the main skeletal muscle ion chloride channel (ClC-1). The clinical diagnosis of MC should be suspected in patients presenting myotonia, warm-up phenomenon, a characteristic electromyographic pattern, and/or family history. Here, we describe the largest cohort of MC Spanish patients including their relatives (up to 102 individuals). Genetic testing was performed by sequencing and multiplex ligation-dependent probe amplification (MLPA). Analysis of selected exons of the gene, causing paramyotonia congenita, was also performed. Mutation spectrum and analysis of a likely founder effect of c.180+3A>T was achieved by haplotype analysis and association tests. Twenty-eight different pathogenic variants were found in the gene, of which 21 were known mutations and seven not described. Gross deletions/duplications were not detected. Four probands had a pathogenic variant in SCN4A. Two main haplotypes were detected in c.180+3A>T carriers and no statistically significant differences were detected between case and control groups regarding the type of haplotype and its frequencies. A diagnostic yield of 51% was achieved; of which 88% had pathogenic variants in and 12% in . The existence of a c.180+3A>T founder effect remains unsolved.
Topics: Chloride Channels; Cohort Studies; Exons; Female; Founder Effect; Haplotypes; Humans; Male; Muscle, Skeletal; Mutation; Myotonia Congenita; NAV1.4 Voltage-Gated Sodium Channel; Polymorphism, Single Nucleotide; Spain
PubMed: 31544778
DOI: No ID Found -
Experimental Neurology Mar 2023It has long been accepted that myotonia (muscle stiffness) in patients with muscle channelopathies is due to myotonic discharges (involuntary firing of action...
It has long been accepted that myotonia (muscle stiffness) in patients with muscle channelopathies is due to myotonic discharges (involuntary firing of action potentials). In a previous study, we identified a novel phenomenon in myotonic muscle: development of plateau potentials, transient depolarizations to near -35 mV lasting for seconds to minutes. In the current study we examined whether plateau potentials contribute to myotonia. A recessive genetic model (ClC mice) with complete loss of muscle chloride channel (ClC-1) function was used to model severe myotonia congenita with complete loss of ClC-1 function and a pharmacologic model using anthracene-9-carboxylic acid (9 AC) was used to model milder myotonia congenita with incomplete loss of ClC-1 function. Simultaneous measurements of action potentials and myoplasmic Ca from individual muscle fibers were compared to recordings of whole muscle force generation. In ClC muscle both myotonia and plateau potentials lasted 10s of seconds to minutes. During plateau potentials lasting 1-2 min, there was a gradual transition from high to low intracellular Ca, suggesting a transition in individual fibers from myotonia to flaccid paralysis in severe myotonia congenita. In 9 AC-treated muscles, both myotonia and plateau potentials lasted only a few seconds and Ca remained elevated during the plateau potentials, suggesting plateau potentials contribute to myotonia without causing weakness. We propose, that in myotonic muscle, there is a novel state in which there is contraction in the absence of action potentials. This discovery provides a mechanism to explain reports of patients with myotonia who suffer from electrically silent muscle contraction lasting minutes.
Topics: Mice; Animals; Myotonia; Myotonia Congenita; Muscle Contraction; Action Potentials; Muscle Fibers, Skeletal; Chloride Channels; Disease Models, Animal
PubMed: 36563835
DOI: 10.1016/j.expneurol.2022.114303 -
Neuromuscular Disorders : NMD Dec 2020In 1876, two articles appeared in Germany in different medical journals under almost the same title "Tonische Krämpfe in willkürlich beweglichen Muskeln in Folge von...
In 1876, two articles appeared in Germany in different medical journals under almost the same title "Tonische Krämpfe in willkürlich beweglichen Muskeln in Folge von ererbter psychischer Disposition (Ataxia muscularis?)" by Julius Thomsen and "Tonische Krämpfe in willkürlich beweglichen Muskeln (Muskelhypertrophie?)" by Adolph Seeligmüller). The first article was by Julius Thomsen (1815-1896) from Kappeln, the second by Adolph Seeligmüller (1837-1912) from Halle (Saale). Both articles dealt with a disease that has later been referred to as myotonia congenita by Adolf Strümpell (1853-1925) in 1881. Carl Westphal (1833-1890), however, ignored the contribution of Seeligmüller and proposed to name the disease Thomsen'sche Krankheit (Thomsen disease). Despite, the temporal priority of Thomsen, the pathogenesis of the disease was more accurately described by Seeligmüller. He recognized the origin of the myotonia in voluntary muscle whereas Thomsen postulated the myotonia as a result of inherited psychological disposition. Thus, Seeligmüller's contribution to myotonia congenita has to be recognized and honored.
Topics: Germany; History, 19th Century; Myotonia Congenita
PubMed: 33221127
DOI: 10.1016/j.nmd.2020.10.004 -
Neurology India 2019
Topics: Adolescent; Humans; Male; Myotonia; Myotonia Congenita; Osteochondrodysplasias; Pedigree
PubMed: 31512670
DOI: 10.4103/0028-3886.266261