"Myotonia congenita"

The mechanism underlying transient weakness in myotonia congenita. In addition to the hallmark muscle stiffness, patients with recessive myotonia congenita (Becker disease) experience debilitating bouts of transient weakness that remain poorly understood despite years of study. We performed intracellular recordings from muscle of both genetic and pharmacologic mouse models of Becker disease Ca1.1 Ca channels contributes to the duration of the plateau. Inhibiting NaPIC with ranolazine prevents the development of plateau potentials and eliminates transient weakness in vivo. These data suggest that targeting NaPIC may be an effective treatment to prevent transient weakness in myotonia congenita.

Chronic inflammatory demyelinating polyradiculoneuropathy relapse after mexiletine withdrawal in a patient with concomitant myotonia congenita: A case report on a potential treatment option. we report on the first case of a woman affected by chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and recessive myotonia congenita (MC), treated with mexiletine. We aimed at describing

A case report: autosomal recessive Myotonia congenita caused by a novel splice mutation (c.1401 + 1G > A) in CLCN1 gene of a Chinese Han patient. Autosomal recessive Myotonia congenita (Becker's disease) is caused by mutations in the CLCN1 gene. The condition is characterized by muscle stiffness during sustained muscle contraction and variable degree of muscle weakness that tends to improve higher than the normal value. Electromyogram showed myotonic discharges. DNA sequence analysis identified a novel splice mutation (c.1401 + 1G > A) and a known mutation (c.1657A > T,p.Ile553Phe). He rapidly responded to treatment with mexiletine 100 mg three times a day for 6 months. This case report of autosomal recessive Myotonia congenita caused by a novel compound heterozygous mutation expands

A case report of recessive myotonia congenita and early onset cognitive impairment: Is it a causal or casual link? 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. A 48-year 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. Recessive myotonia congenita was diagnosed. Further studies should

Novel Mutations in SCN4A Gene Cause Myotonia Congenita with Scoliosis

Myotonia Congenita Can Be Mistaken as Paroxysmal Kinesigenic Dyskinesia

Open-label trial of ranolazine for the treatment of myotonia congenita. To determine open-label, pilot study whether ranolazine could improve signs and symptoms of myotonia and muscle stiffness in patients with myotonia congenita (MC). Thirteen participants were assessed at baseline and 2, 4, and 5 weeks. Ranolazine was started after baseline assessment (500 mg twice daily), increased stiffness. The findings of this study suggest that ranolazine should be investigated in a larger controlled study. This study provides Class IV evidence that ranolazine improves myotonia in myotonia congenita.

Electrophysiological characteristics of R47W and A298T mutations in CLC-1 of myotonia congenita patients and evaluation of clinical features Myotonia congenita (MC) is a genetic disease that displays impaired relaxation of skeletal muscle and muscle hypertrophy. This disease is mainly caused by mutations of that encodes human skeletal muscle chloride channel (CLC-1). CLC-1 is a voltage gated chloride channel that activates upon depolarizing potentials and play a major role in stabilization of resting membrane potentials in skeletal muscle. In this study, we report 4 unrelated Korean patients diagnosed with myotonia congenita and their clinical features. Sequence analysis of all coding regions of the patients was performed and mutation, R47W and A298T, was commonly identified. The patients

Multidisciplinary study of a new ClC-1 mutation causing myotonia congenita: a paradigm to understand and treat ion channelopathies Myotonia congenita is an inherited disease that is characterized by impaired muscle relaxation after contraction caused by loss-of-function mutations in the skeletal muscle ClC-1 channel. We report a novel ClC-1 mutation, T335N, that is associated with a mild ., Camerino, G. M., Mangiatordi, G. F., Conte, E., Maggi, L., Brugnoni, R., Musaraj, K., Caloiero, R., Alberga, D., Marsano, R. M., Ricci, G., Siciliano, G., Nicolotti, O., Mora, M., Bernasconi, P., Desaphy, J.-F., Mantegazza, R., Camerino, D. C. Multidisciplinary study of a new ClC-1 mutation causing myotonia congenita: a paradigm to understand and treat ion channelopathies.

Bodybuilding championships and myotonia congenita

A Large Dominant Myotonia Congenita Family with a V1293I Mutation in SCN4A

Sodium channel slow inactivation as a therapeutic target for myotonia congenita. Patients with myotonia congenita have muscle hyperexcitability due to loss-of-function mutations in the chloride channel in skeletal muscle, which causes spontaneous firing of muscle action potentials (myotonia), producing muscle stiffness. In patients, muscle stiffness lessens with exercise, a change known as the warmup phenomenon. Our goal was to identify the mechanism underlying warmup and to use this information to guide development of novel therapy. To determine the mechanism underlying warmup, we used a recently discovered drug to eliminate muscle contraction, thus allowing prolonged intracellular recording from individual muscle fibers during induction of warmup in a mouse model of myotonia congenita

In vitro muscle contracture investigations on the malignant hyperthermia like episodes in myotonia congenita. A common form of congenital myotonia, myotonia congenita (MC), is caused by mutations in the skeletal muscle Cl(-) channel gene type 1 (CLCN1). Due to the reduced Cl(-) conductance of the mutated channels, the patients may develop generalized muscle rigidity and hypermetabolism during

A new explanation for recessive myotonia congenita: Exon deletions and duplications in CLCN1. To assess whether exon deletions or duplications in CLCN1 are associated with recessive myotonia congenita (MC). We performed detailed clinical and electrophysiologic characterization in 60 patients with phenotypes consistent with MC. DNA sequencing of CLCN1 followed by multiplex ligation-dependent

Myotonia congenita with strabismus in a large family with a mutation in the SCN4A gene To determine the genetic basis of myotonia congenita (MC) and strabismus in a large Caucasian family. Seven patients making up four generations of a family with MC and strabismus were recruited. All patients had at least one standard ophthalmic examination, including best-corrected visual acuity, refraction

Disease-causing mutations C277R and C277Y modify gating of human ClC-1 chloride channels in myotonia congenita Myotonia congenita is a genetic condition that is caused by mutations in the muscle chloride channel gene CLCN1 and characterized by delayed muscle relaxation and muscle stiffness. We here investigate the functional consequences of two novel disease-causing missense mutations, C277R

patients were aged 18 to 65 years with genetically defined myotonia congenita (a chloride channelopathy) or paramyotonia congenita (a sodium channelopathy). They had myotonia symptoms severe enough to justify treatment with mexiletine based on clinical criteria (involving at least two segments [upper limb, 3 lower limb or face]) and disabling criteria (impacting on at least three of seven daily week. Randomisation was stratified by diagnoses (myotonia congenita or paramyotonia congenita).2 The primary outcome was the score of stiffness severity which was self-reported by the patient using a visual analogue scale (VAS) ranging from 0 (no stiffness) to 100 (worst possible stiffness). The statistical plan tested for potential carry-over effect between period 1 and period 2 by comparing

were aged 18 to 65 years with genetically defined myotonia congenita (a chloride channelopathy) or paramyotonia congenita (a sodium channelopathy). They had myotonia symptoms severe enough to justify treatment with mexiletine based on clinical criteria (involving at least two segments [upper limb, 3 lower limb or face]) and disabling criteria (impacting on at least three of seven daily activities . Randomisation was stratified by diagnoses (myotonia congenita or paramyotonia congenita).2 The primary outcome was the score of stiffness severity which was self-reported by the patient using a visual analogue scale (VAS) ranging from 0 (no stiffness) to 100 (worst possible stiffness). The statistical plan tested for potential carry-over effect between period 1 and period 2 by comparing the difference between

is identified with confidence, interpretation of the clinical significance and inheritance pattern of variants can be challenging. We report our approach to evaluating variants in the skeletal muscle chloride channel ClC-1 identified in 223 probands with myotonia congenita as an example of these challenges. Sequencing of CLCN1, the gene that encodes CLC-1, is central to the diagnosis of myotonia congenita with dominant functional features or dominant inheritance pattern of myotonia congenita. Our data help provide an initial estimate of the anticipated inheritance pattern based on the location of a novel variant and shows that systematic functional characterization can significantly refine the assessment of risk of an associated inheritance pattern and consequently the clinical and genetic counselling.

unclear since they have usually not been validated against robust functional assays. We compare nine widely used in silico predictive tools including more recently developed tools (EVE and REVEL) with detailed cell-based electrophysiology for 126 CLCN1 variants discovered in patients with the skeletal muscle channelopathy myotonia congenita. We found poor accuracy for most tools. The highest accuracy