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Iranian Journal of Neurology Jan 2016The myotonic disorders are a heterogeneous group of genetically determined diseases that are unified by the presence of myotonia, which is defined as failure of muscle... (Review)
Review
The myotonic disorders are a heterogeneous group of genetically determined diseases that are unified by the presence of myotonia, which is defined as failure of muscle relaxation after activation. The presentation of these disorders can range from asymptomatic electrical myotonia, as seen in some forms of myotonia congenita (MC), to severe disability with muscle weakness, cardiac conduction defects, and other systemic features as in myotonic dystrophy type I (DM1). In this review, we describe the clinical features and pathophysiology of the different myotonic disorders, their laboratory and electrophysiologic findings and briefly review the currently available treatments.
PubMed: 27141276
DOI: No ID Found -
BMJ Case Reports May 2021
Topics: Hand Strength; Humans; Myotonia; Myotonia Congenita; Myotonic Dystrophy
PubMed: 33958356
DOI: 10.1136/bcr-2020-240779 -
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 -
Journal of Neuromuscular Diseases 2023Myotonia congenita is the most common form of nondystrophic myotonia and is caused by Mendelian inherited mutations in the CLCN1 gene encoding the voltage-gated chloride...
BACKGROUND
Myotonia congenita is the most common form of nondystrophic myotonia and is caused by Mendelian inherited mutations in the CLCN1 gene encoding the voltage-gated chloride channel of skeletal muscle.
OBJECTIVE
The study aimed to describe the clinical and genetic spectrum of Myotonia congenita in a large pediatric cohort.
METHODS
Demographic, genetic, and clinical data of the patients aged under 18 years at time of first clinical attendance from 11 centers in different geographical regions of Türkiye were retrospectively investigated.
RESULTS
Fifty-four patients (mean age:15.2 years (±5.5), 76% males, with 85% Becker, 15% Thomsen form) from 40 families were included. Consanguineous marriage rate was 67%. 70.5% of patients had a family member with Myotonia congenita. The mean age of disease onset was 5.7 (±4.9) years. Overall 23 different mutations (2/23 were novel) were detected in 52 patients, and large exon deletions were identified in two siblings. Thomsen and Becker forms were observed concomitantly in one family. Carbamazepine (46.3%), mexiletine (27.8%), phenytoin (9.3%) were preferred for treatment.
CONCLUSIONS
The clinical and genetic heterogeneity, as well as the limited response to current treatment options, constitutes an ongoing challenge. In our cohort, recessive Myotonia congenita was more frequent and novel mutations will contribute to the literature.
Topics: Male; Humans; Child; Adolescent; Aged; Infant; Child, Preschool; Female; Myotonia Congenita; Retrospective Studies; Chloride Channels; Mutation; Muscle, Skeletal
PubMed: 37355912
DOI: 10.3233/JND-230046 -
Frontiers in Pediatrics 2021-related myotonia congenita (MC) is one of the most common forms of non-dystrophic myotonia, in which muscle relaxation is delayed after voluntary or evoked...
-related myotonia congenita (MC) is one of the most common forms of non-dystrophic myotonia, in which muscle relaxation is delayed after voluntary or evoked contraction. However, there is limited data of clinical and molecular spectrum of MC patients in China. Five patients with myotonia congenita due to mutations in gene were enrolled, which were identified through trio-whole-exome sequencing or panel-based next-generation sequencing test. The clinical presentation, laboratory data, electrophysiological tests, muscular pathology feature, and genetic results were collected and reviewed. We also searched all previously reported cases of MC patients with genetic diagnosis in Chinese populations, and their data were reviewed. The median onset age of five patients was 3.0 years old, ranging from 1.0 to 5.0 years old, while the median age of admit was 5.0 years old, ranging from 3.5 to 8.8 years old. Five patients complained of muscle stiffness when rising from chairs or starting to climb stairs (5/5, 100.0%), four patients complained of delayed relaxation of their hands after forceful grip (4/5, 80.0%), all of which improved with exercise (warm-up phenomenon) (5/5, 100%). Electromyogram was conducted in five patients, which all revealed myotonic change (100%). Genetic tests revealed nine potential disease-causing variants in gene, including two novel variants: c.962T>A (p.V321E) and c.1250A>T (p.E417V). Literature review showed that 43 MC Chinese patients with genetic diagnosis have been reported till now (including our five patients). Forty-seven variants in gene were found, which consisted of 33 missense variants, 6 nonsense variants, 5 frame-shift variants, and 3 splicing variants. Variants in exon 8, 15, 12, and 16 were most prevalent, while the most common variants were c.892G>A (p.A298T) ( = 9), c.139C>T (p.R47W) ( = 3), c.1205C>T(p.A402V) ( = 3), c.1657A>T (p.I553F) ( = 3), c.1679T>C (p.M560T) ( = 3), c.350A>G (p.D117G) ( = 2), c.762C>G (p.C254W) ( = 2), c.782A>G (P.Y261C) ( = 2), and c.1277C>A (p.T426N) ( = 2). Our results reported five -related MC patients, which expanded the clinical and genetic spectrum of MC patients in China. Based on literature review, 43MC Chinese patients with genetic diagnosis have been reported till now, and variants in exon eight were most prevalent in Chinese MC patients while c.892G>A (p.A298T) was probably a founder mutation.
PubMed: 34790634
DOI: 10.3389/fped.2021.759505 -
Muscle & Nerve Oct 2017Exercise has not been investigated in myotonia congenita (MC). We investigated whether regular aerobic training can reduce myotonia and improve fitness.
INTRODUCTION
Exercise has not been investigated in myotonia congenita (MC). We investigated whether regular aerobic training can reduce myotonia and improve fitness.
METHODS
Untrained patients with MC (age: 24-62 years; n = 6) completed 28 ± 3 sessions of 30-minute cycle ergometer training at 75% of maximal capacity for 11 ± 1 weeks. Fitness was evaluated by maximal oxygen uptake. The level of myotonia was assessed by the Myotonia Behavior Scale, 14 step stair test, timed up and go test, and hand and eye closure-open tests.
RESULTS
Training increased fitness by 9% (95% confidence interval [CI], 1-17%; P = 0.02) and maximal workload by 10% (95% CI, 3-18%; P = 0.03). None of the myotonia tests changed in a clinically meaningful way.
CONCLUSIONS
Regular endurance training improves fitness and maximal workload performance in patients with MC. The lack of creatine kinase elevations indicates that muscle damage did not occur. Improved fitness, however, did not change myotonic symptoms in this small cohort. Muscle Nerve 56: 696-699, 2017.
Topics: Adult; Exercise; Exercise Therapy; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myotonia; Myotonia Congenita; Physical Endurance; Physical Fitness; Treatment Outcome
PubMed: 28039888
DOI: 10.1002/mus.25549 -
Channels (Austin, Tex.) Dec 2024Myotonia congenita (MC) is a rare hereditary muscle disease caused by variants in the CLCN1 gene. Currently, the correlation of phenotype-genotype is still uncertain...
Myotonia congenita (MC) is a rare hereditary muscle disease caused by variants in the CLCN1 gene. Currently, the correlation of phenotype-genotype is still uncertain between dominant-type Thomsen (TMC) and recessive-type Becker (BMC). The clinical data and auxiliary examinations of MC patients in our clinic were retrospectively collected. Electromyography was performed in 11 patients and available family members. Whole exome sequencing was conducted in all patients. The clinical and laboratory data of Chinese MC patients reported from June 2004 to December 2022 were reviewed. A total of 11 MC patients were included in the study, with a mean onset age of 12.64 ± 2.73 years. The main symptom was muscle stiffness of limbs. Warm-up phenomenon and percussion myotonia were found in all patients. Electromyogram revealed significant myotonic charges in all patients and two asymptomatic carriers, while muscle MRI and biopsy showed normal or nonspecific changes. Fourteen genetic variants including 6 novel variants were found in CLCN1. Ninety-eight Chinese patients were re-analyzed and re-summarized in this study. There were no significant differences in the demographic data, clinical characteristics, and laboratory findings between 52 TMC and 46 BMC patients. Among the 145 variants in CLCN1, some variants, including the most common variant c.892 G>A, could cause TMC in some families and BMC in others. This study expanded the clinical and genetic spectrum of Chinese patients with MC. It was difficult to distinguish between TMC and BMC only based on the clinical, laboratory, and genetic characteristics.
Topics: Humans; Myotonia Congenita; Male; Female; Chloride Channels; Child; Adolescent; Asian People; Adult; Young Adult; Electromyography; Retrospective Studies; China; Mutation; East Asian People
PubMed: 38720415
DOI: 10.1080/19336950.2024.2349823 -
Annals of Neurology Aug 2020Myotonia is caused by involuntary firing of skeletal muscle action potentials and causes debilitating stiffness. Current treatments are insufficiently efficacious and...
OBJECTIVE
Myotonia is caused by involuntary firing of skeletal muscle action potentials and causes debilitating stiffness. Current treatments are insufficiently efficacious and associated with side effects. Myotonia can be triggered by voluntary movement (electrically induced myotonia) or percussion (mechanically induced myotonia). Whether distinct molecular mechanisms underlie these triggers is unknown. Our goal was to identify ion channels involved in mechanically induced myotonia and to evaluate block of the channels involved as a novel approach to therapy.
METHODS
We developed a novel system to enable study of mechanically induced myotonia using both genetic and pharmacologic mouse models of myotonia congenita. We extended ex vivo studies of excitability to in vivo studies of muscle stiffness.
RESULTS
As previous work suggests activation of transient receptor potential vanilloid 4 (TRPV4) channels by mechanical stimuli in muscle, we examined the role of this cation channel. Mechanically induced myotonia was markedly suppressed in TRPV4-null muscles and in muscles treated with TRPV4 small molecule antagonists. The suppression of mechanically induced myotonia occurred without altering intrinsic muscle excitability, such that myotonia triggered by firing of action potentials (electrically induced myotonia) was unaffected. When injected intraperitoneally, TRPV4 antagonists lessened the severity of myotonia in vivo by approximately 80%.
INTERPRETATION
These data demonstrate that there are distinct molecular mechanisms triggering electrically induced and mechanically induced myotonia. Our data indicates that activation of TRPV4 during muscle contraction plays an important role in triggering myotonia in vivo. Elimination of mechanically induced myotonia by TRPV4 inhibition offers a new approach to treating myotonia. ANN NEUROL 2020;88:297-308.
Topics: Animals; Anthracenes; Isometric Contraction; Mice; Mice, Knockout; Morpholines; Muscle, Skeletal; Myotonia Congenita; Pyrroles; TRPV Cation Channels
PubMed: 32418267
DOI: 10.1002/ana.25780 -
F1000Research 2018By definition, congenital myopathy typically presents with skeletal muscle weakness and hypotonia at birth. Traditionally, congenital myopathy subtypes have been... (Review)
Review
By definition, congenital myopathy typically presents with skeletal muscle weakness and hypotonia at birth. Traditionally, congenital myopathy subtypes have been predominantly distinguished on the basis of the pathological hallmarks present on skeletal muscle biopsies. Many genes cause congenital myopathies when mutated, and a burst of new causative genes have been identified because of advances in gene sequencing technology. Recent discoveries include extending the disease phenotypes associated with previously identified genes and determining that genes formerly known to cause only dominant disease can also cause recessive disease. The more recently identified congenital myopathy genes account for only a small proportion of patients. Thus, the congenital myopathy genes remaining to be discovered are predicted to be extremely rare causes of disease, which greatly hampers their identification. Significant progress in the provision of molecular diagnoses brings important information and value to patients and their families, such as possible disease prognosis, better disease management, and informed reproductive choice, including carrier screening of parents. Additionally, from accurate genetic knowledge, rational treatment options can be hypothesised and subsequently evaluated and in animal models. A wide range of potential congenital myopathy therapies have been investigated on the basis of improved understanding of disease pathomechanisms, and some therapies are in clinical trials. Although large hurdles remain, promise exists for translating treatment benefits from preclinical models to patients with congenital myopathy, including harnessing proven successes for other genetic diseases.
Topics: Animals; Genetic Testing; Humans; Molecular Diagnostic Techniques; Myotonia Congenita
PubMed: 30631434
DOI: 10.12688/f1000research.16422.1 -
The American Journal of the Medical... Jun 2022
Topics: Humans; Mutation; Myotonia Congenita
PubMed: 33531161
DOI: 10.1016/j.amjms.2020.11.010