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The Indian Medical Gazette Jul 1945
Topics: Humans; Leishmaniasis; Myotonia; Myotonia Congenita
PubMed: 21007261
DOI: No ID Found -
Neurology Jun 2012To assess whether exon deletions or duplications in CLCN1 are associated with recessive myotonia congenita (MC).
OBJECTIVE
To assess whether exon deletions or duplications in CLCN1 are associated with recessive myotonia congenita (MC).
METHODS
We performed detailed clinical and electrophysiologic characterization in 60 patients with phenotypes consistent with MC. DNA sequencing of CLCN1 followed by multiplex ligation-dependent probe amplification to screen for exon copy number variation was undertaken in all patients.
RESULTS
Exon deletions or duplications in CLCN1 were identified in 6% of patients with MC. Half had heterozygous exonic rearrangements. The other 2 patients (50%), with severe disabling infantile onset myotonia, were identified with both a homozygous mutation, Pro744Thr, which functional electrophysiology studies suggested was nonpathogenic, and a triplication/homozygous duplication involving exons 8-14, suggesting an explanation for the severe phenotype.
CONCLUSIONS
These data indicate that copy number variation in CLCN1 may be an important cause of recessive MC. Our observations suggest that it is important to check for exon deletions and duplications as part of the genetic analysis of patients with recessive MC, especially in patients in whom sequencing identifies no mutations or only a single recessive mutation. These results also indicate that additional, as yet unidentified, genetic mechanisms account for cases not currently explained by either CLCN1 point mutations or exonic deletions or duplications.
Topics: Adolescent; Adult; Base Sequence; Chloride Channels; DNA Copy Number Variations; Exons; Female; Genetic Testing; Genotype; Humans; Male; Myotonia Congenita; Sequence Deletion
PubMed: 22649220
DOI: 10.1212/WNL.0b013e318259e19c -
The Journal of Clinical Investigation Oct 1971In isolated fiber bundles of external intercostal muscle from each of 13 normal volunteers and each of 6 patients with myotonia congenita, some or all of the following...
Cable parameters, sodium, potassium, chloride, and water content, and potassium efflux in isolated external intercostal muscle of normal volunteers and patients with myotonia congenita.
In isolated fiber bundles of external intercostal muscle from each of 13 normal volunteers and each of 6 patients with myotonia congenita, some or all of the following were measured: concentrations of Na(+), K(+), and Cl(-), extracellular volume, water content, K(+) efflux, fiber size, fiber cable parameters, and fiber resting potentials. Muscle from patients with myotonia congenita differed significantly (0.001
myotonia congenita vs. normal): the membrane resistance was greater (5729 vs. 2619 omega.cm(2)), the internal resistivity was less (75.0 vs. 123.2 omega.cm), the water content was less (788.2 vs. 808.2 ml/kg wet weight), and the mean resting potential was greater (68 vs. 61 mv).NO SIGNIFICANT DIFFERENCES WERE FOUND WITH RESPECT TO THE FOLLOWING VARIABLES: K(+) content (73.5 vs. 66.7 mEq/kg wet weight) and the calculated intracellular K(+) concentration (215 vs. 191 mEq/liter fiber water), fiber capacitance (5.90 vs. 5.15 muf/cm(2)), Na(+) content (97.7 vs. 94.1 mEq/kg wet weight), Cl(-) content (79.0 vs. 74.7 mEq/kg wet weight), mannitol extracellular volume (45.1 vs. 46.6 cc/100 g wet weight), and K(+) efflux (23.2 vs. 21.5 moles x 10(-12) cm(-2).sec(-1)). These abnormalities of skeletal muscle in human myotonia congenita are like those of skeletal muscle in goats with hereditary myotonia. We tentatively conclude that a decreased Cl(-) permeability accounts for some of the abnormal electrical properties of skeletal muscle in myotonia congenita.
Topics: Action Potentials; Adult; Biological Transport; Biopsy; Chlorides; Extracellular Space; Female; Humans; Intercostal Muscles; Ions; Lipids; Male; Myofibrils; Myotonia Congenita; Potassium; Potassium Isotopes; Radioisotope Dilution Technique; Sodium; Water
PubMed: 4940295
DOI: 10.1172/JCI106703 -
Neuroscience Bulletin Dec 2014Paroxysmal kinesigenic dyskinesia (PKD) and myotonia congenita (MC) are independent disorders that share some clinical features. We aimed to investigate the sequences of...
Paroxysmal kinesigenic dyskinesia (PKD) and myotonia congenita (MC) are independent disorders that share some clinical features. We aimed to investigate the sequences of PRRT2 and CLCN1 in a proband diagnosed with PKD and suspected MC. Clinical evaluation and auxiliary examinations were performed. Direct sequencing of the entire coding regions of the PRRT2 and CLCN1 genes was conducted. Haplotype analysis confirmed the relationships among the family members. The proband suffered choreoathetosis attacks triggered by sudden movements, and lower-limb weakness and stiffness that worsened in cold weather. Carbamazepine monotherapy completely controlled his choreoathetosis and significantly relieved his limb weakness and stiffness. His father, when young, had similar limb stiffness, while his mother and brother were asymptomatic. Genetic analysis revealed that the proband and his father harbored a PRRT2 c.649dupC mutation, and CLCN1 c.1723C>T and c.2492A>G mutations. His brother carried only the two CLCN1 mutations. None of these mutations were identified in his mother and 150 unrelated controls. This is the first report showing the coexistence of PRRT2 and CLCN1 mutations. Our results also indicate that both the PRRT2 and CLCN1 genes need to be screened if we fail to identify PRRT2 mutations in PKD patients or CLCN1 mutations in MC patients.
Topics: Adult; Chloride Channels; Chorea; Dystonia; Humans; Male; Membrane Proteins; Mutation; Myotonia Congenita; Nerve Tissue Proteins; Young Adult
PubMed: 25205014
DOI: 10.1007/s12264-014-1467-7 -
Journal of Veterinary Internal Medicine Jan 2020Paramyotonia congenita and Brody disease are well-described conditions in humans, characterized by exercise-induced myotonic-like muscle stiffness. A syndrome similar to...
BACKGROUND
Paramyotonia congenita and Brody disease are well-described conditions in humans, characterized by exercise-induced myotonic-like muscle stiffness. A syndrome similar to Brody disease has been reported in cattle. Reports of a similar syndrome in dogs are scarce.
OBJECTIVES
To define and describe the clinical, diagnostic, and genetic features and disease course of paradoxical pseudomyotonia in Spaniel dogs.
ANIMALS
Seven client-owned dogs (4 English Springer Spaniels and 3 English Cocker Spaniels) with clinically confirmed episodes of exercise-induced generalized myotonic-like muscle stiffness.
METHODS
Sequential case study.
RESULTS
All dogs were <24 months of age at onset. The episodes of myotonic-like generalized muscle stiffness always occurred with exercise, and spontaneously resolved with rest in <45 seconds in all but 1 dog. Extreme outside temperatures seemed to considerably worsen episode frequency and severity in most dogs. Complete blood count, serum biochemistry including electrolytes, urinalysis, brain magnetic resonance imaging, cerebrospinal fluid analysis, electromyography, motor nerve conduction velocity, ECG, and echocardiography were unremarkable. Muscle biopsy samples showed moderate but nonspecific muscle atrophy. The episodes seemed to remain stable or decrease in severity and frequency in 6/7 dogs, and often could be decreased or prevented by avoiding the episode triggers. The underlying genetic cause is not identified yet, because no disease-causing variants could be found in the coding sequence or splice sites of the 2 major candidate genes, SCN4A and ATP2A1.
CONCLUSIONS AND CLINICAL IMPORTANCE
Paradoxical pseudomyotonia is a disease affecting Spaniels. It is of variable severity but benign in most cases.
Topics: Animals; Dog Diseases; Dogs; Isaacs Syndrome; Physical Conditioning, Animal
PubMed: 31729100
DOI: 10.1111/jvim.15660 -
European Journal of Neurology Nov 2012Fatigue and pain have been previously shown to be important determinants for decreasing quality of life (QoL) in one report in patients with non-dystrophic myotonia. The...
BACKGROUND AND PURPOSE
Fatigue and pain have been previously shown to be important determinants for decreasing quality of life (QoL) in one report in patients with non-dystrophic myotonia. The aims of our study were to assess QoL in skeletal muscle channelopathies (SMC) using INQoL (individualized QoL) and SF-36 questionnaires.
METHODS
We administered INQoL and SF-36 to 66 Italian patients with SMC (26: periodic paralysis, 36: myotonia congenita and 4: Andersen-Tawil) and compared the results in 422 patients with myotonic dystrophies (DM1: 382; and DM2: 40).
RESULTS
(i) INQoL index in SMC is similar to that in DMs (P = 0.79). (ii) Patients with myotonia congenita have the worst perception of QoL. (iii) Myotonia has the most detrimental effect on patients with myotonia congenita, followed by patients with DM2 and then by patients with DM1 and hyperkalemic periodic paralysis. (iv) Pain is a significant complaint in patients with myotonia congenita, hypokalemic periodic paralysis and DM2 but not in DM1. (v) Fatigue has a similar detrimental effect on all patient groups except for patients with hyperkalemic periodic paralysis in whom muscle weakness and myotonia more than fatigue affect QoL perception. (vi) Muscle symptoms considered in INQoL correlate with physical symptoms assessed by SF-36 (R from -0.34 to -0.76).
CONCLUSIONS
QoL perception in patients with SMC is similar to that of patients with DMs, chronic multisystem disabling conditions. Our results provide information to target treatment and health care of these patients. The sensitivity of INQoL to changes in QoL in the SMC needs to be further explored in longitudinal studies.
Topics: Adult; Channelopathies; Female; Humans; Male; Middle Aged; Quality of Life; Surveys and Questionnaires
PubMed: 22607270
DOI: 10.1111/j.1468-1331.2012.03751.x -
Medicine Jun 2018Myotonia congenita (MC) is a non-dystrophic myotonia inherited either in dominant (Thomsen) or recessive (Becker) form. MC is due to an abnormal functioning of skeletal...
RATIONALE
Myotonia congenita (MC) is a non-dystrophic myotonia inherited either in dominant (Thomsen) or recessive (Becker) form. MC is due to an abnormal functioning of skeletal muscle voltage-gated chloride channel (CLCN1), but the genotype/phenotype correlation remains unclear.
PATIENT CONCERNS
A 48-year-old man, from consanguineous parents, presented with a fixed muscle weakness, muscle atrophy, and a cognitive impairment. Notably, his brother presented the same mutation but with a different phenotype, mainly involving cognitive function.
INTERVENTIONS
The patient was submitted to cognitive assessment, needle electromyography, brain and muscle MRI, and genetic analysis.
OUTCOMES
The Milan Overall Dementia Assessment showed short-term memory, verbal fluency and verbal intelligence impairment. His genetic analysis showed a recessive splice-site mutation in the CLCN1 gene (IVS19+2T>A). Muscle MRI revealed a symmetric and bilateral fat infiltration of the tensor of fascia lata, gluteus medius, and gluteus maximus muscles, associated to mild atrophy.
DIAGNOSIS
Recessive myotonia congenita was diagnosed.
LESSONS
Further studies should establish if and to which extent the CLCN1 mutation is responsible for this c MC phenotype, taking into account a gene-gene and /or a gene-environment.
Topics: Brain; Chloride Channels; Cognitive Dysfunction; Electromyography; Genetic Testing; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Muscle Weakness; Muscle, Skeletal; Muscular Atrophy; Mutation; Myotonia Congenita; Phenotype
PubMed: 29851785
DOI: 10.1097/MD.0000000000010785 -
Annals of Neurology Feb 2011To improve the accuracy of genotype prediction and guide genetic testing in patients with muscle channelopathies we applied and refined specialized electrophysiological...
OBJECTIVE
To improve the accuracy of genotype prediction and guide genetic testing in patients with muscle channelopathies we applied and refined specialized electrophysiological exercise test parameters.
METHODS
We studied 56 genetically confirmed patients and 65 controls using needle electromyography, the long exercise test, and short exercise tests at room temperature, after cooling, and rewarming.
RESULTS
Concordant amplitude-and-area decrements were more reliable than amplitude-only measurements when interpreting patterns of change during the short exercise tests. Concordant amplitude-and-area pattern I and pattern II decrements of >20% were 100% specific for paramyotonia congenita and myotonia congenita, respectively. When decrements at room temperature and after cooling were <20%, a repeat short exercise test after rewarming was useful in patients with myotonia congenita. Area measurements and rewarming distinguished true temperature sensitivity from amplitude reduction due to cold-induced slowing of muscle fiber conduction. In patients with negative short exercise tests, symptomatic eye closure myotonia predicted sodium channel myotonia over myotonia congenita. Distinctive "tornado-shaped" neuromyotonia-like discharges may be seen in patients with paramyotonia congenita. In the long exercise test, area decrements from pre-exercise baseline were more sensitive than amplitude decrements-from-maximum-compound muscle action potential (CMAP) in patients with Andersen-Tawil syndrome. Possible ethnic differences in the normative data of the long exercise test argue for the use of appropriate ethnically-matched controls.
INTERPRETATION
Concordant CMAP amplitude-and-area decrements of >20% allow more reliable interpretation of the short exercise tests and aid accurate DNA-based diagnosis. In patients with negative exercise tests, specific clinical features are helpful in differentiating sodium from chloride channel myotonia. A modified algorithm is suggested.
Topics: Adolescent; Adult; Aged; Channelopathies; Electromyography; Exercise Test; Female; Humans; Male; Middle Aged; Muscle Weakness; Muscle, Skeletal; Myotonic Disorders
PubMed: 21387378
DOI: 10.1002/ana.22238 -
The Journal of Small Animal Practice Oct 1998FELINE infections peritonitis (FIP) is a systemic, fatal, immune‐mediated vasculitis caused by a feline coronavirus (FCoV). Historically, FIP virus (FIPV) and feline...
FELINE infections peritonitis (FIP) is a systemic, fatal, immune‐mediated vasculitis caused by a feline coronavirus (FCoV). Historically, FIP virus (FIPV) and feline enteritis by a feline enteric coronavirus (FECV). Recent studies have shown that there is essentially only one FCoV in the field, although laboratory strains may vary in virulence.
Topics: Animals; Cat Diseases; Cats; Myotonia Congenita
PubMed: 9816575
DOI: 10.1111/j.1748-5827.1998.tb03690.x -
Genes Jun 2023Congenital myopathies are a group of clinically, genetically, and histologically heterogeneous diseases caused by mutations in a large group of genes. One of these is ,... (Review)
Review
BACKGROUND
Congenital myopathies are a group of clinically, genetically, and histologically heterogeneous diseases caused by mutations in a large group of genes. One of these is , which is recognized as the cause of Dihydropyridine Receptor Congenital Myopathy.
METHODS
To better characterize the phenotypic spectrum of myopathy, we conducted a systematic review of cases in the literature through three electronic databases following the PRISMA guidelines. We selected nine articles describing 23 patients with heterozygous, homozygous, or compound heterozygous mutations in and we added one patient with a compound heterozygous mutation in (c.1394-2A>G; c.1724T>C, p.L575P) followed at our Institute. We collected clinical and genetic data, muscle biopsies, and muscle MRIs when available.
RESULTS
The phenotype of this myopathy is heterogeneous, ranging from more severe forms with a lethal early onset and mild-moderate forms with a better clinical course.
CONCLUSIONS
Our patient presented a phenotype compatible with the mild-moderate form, although she presented peculiar features such as a short stature, myopia, mild sensorineural hearing loss, psychiatric symptoms, and posterior-anterior impairment gradient on thigh muscle MRI.
Topics: Female; Humans; Calcium Channels, L-Type; Muscular Diseases; Mutation; Muscle, Skeletal; Phenotype; Myotonia Congenita
PubMed: 37510268
DOI: 10.3390/genes14071363