"Paramyotonia congenita"

Open-label trial of ranolazine for the treatment of paramyotonia congenita. Paramyotonia congenita (PMC) is a nondystrophic myotonic disorder that is believed to be caused by a defect in Na 1.4 sodium channel inactivation. Ranolazine, which acts by enhancing slow inactivation of sodium channels, has been proposed as a therapeutic option, but in vivo studies are lacking. We conducted an open

Substitutions of the S4DIV R2 residue (R1451) in NaV1.4 lead to complex forms of paramyotonia congenita and periodic paralyses Mutations in Na1.4, the skeletal muscle voltage-gated Na channel, underlie several skeletal muscle channelopathies. We report here the functional characterization of two substitutions targeting the R1451 residue and resulting in 3 distinct clinical phenotypes. The R1451L

N1366S mutation of human skeletal muscle sodium channel causes paramyotonia congenita Paramyotonia congenita is a hereditary channelopathy caused by missense mutations in the SCN4A gene, which encodes the α subunit of the human skeletal muscle voltage-gated sodium channel NaV1.4. Affected individuals suffered from myotonia and paralysis of muscles, which were aggravated by exposure to cold. We report a three-generation Chinese family with patients presenting paramyotonia congenita and identify a novel N1366S mutation of NaV1.4. Whole-cell electrophysiological recordings of the N1366S channel reveal a gain-of-function change of gating in response to cold. Modelling and molecular dynamic simulation data suggest that an arginine-to-serine substitution at position 1366 increases the distance

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

Efficacy and safety of mexiletine in non-dystrophic myotonias: A randomised, double-blind, placebo-controlled, cross-over study. The MYOMEX study was a multicentre, randomised, double-blind, placebo-controlled, cross-over study aimed to compare the effects of mexiletine vs. placebo in patients with myotonia congenita (MC) and paramyotonia congenita (PC). The primary endpoint was the self-reported

A unique presentation and etiology of neonatal paradoxical vocal fold motion. We present a unique case of intermittent paradoxical vocal fold motion (PVFM) as the presenting symptom of a rare underlying neuromuscular disorder in a neonate. Paramyotonia congenita (PC) is an autosomal dominant condition that typically presents in infancy with myotonic episodes affecting the skeletal muscles. Our

myotonia, paramyotonia congenita, hyperkalemic periodic paralysis, hypokalemic periodic paralysis, congenital myasthenia, and congenital myopathy with hypotonia. Mutation-specific alternations of Na1.4 function explain the mechanistic basis for the diverse phenotypes and identify opportunities for strategic intervention to modify the burden of disease.

with clinical myotonia and genetically confirmed myotonia congenita and paramyotonia congenita for investigation at the Copenhagen Neuromuscular Center. A pharmacy produced the medication and placebo, and randomized patients in blocks of 10. Participants and investigators were all blinded to treatment until the end of the trial. In two 8-week periods, oral lamotrigine or placebo capsules were provided once

properties and kinetics of activation and inactivation of the Na conductance. This was useful in analysing repetitive firing associated with paramyotonia congenita in skeletal muscle. Similarly, genetic cardiac Na channel abnormalities increasing I are implicated in triggering phenomena of automaticity, early and delayed afterdepolarisations and arrhythmic substrate. This review illustrates a wide range

dystrophy 2.88/100,000 (95% CI 2.31-3.45), periodic paralysis 1.72/100,000 (95% CI 1.28-2.15), myotonia congenita 0.32/100,000 (95% CI 0.18-0.56), paramyotonia congenita 0.15/100,000 (95% CI 0.06-0.34), Kennedy disease 0.83/100,000 (95% CI 0.40-1.27), Lambert-Eaton myasthenic syndrome 0.29/100,000 (95% CI 0.11-0.47), myasthenia gravis 15.12/100,000 (95% CI 13.82-16.42), and sporadic inclusion body

Sequence CLCN1 and SCN4A in patients with Nondystrophic myotonias in Chinese populations: Genetic and pedigree analysis of 10 families and review of the literature Myotonia congenita (MC), paramyotonia congenita (PC) and sodium channel myotonias(SCM) were belonged to Non-dystrophic myotonias, in which muscle relaxation is delayed after voluntary or evoked contraction. These diseases can

inactivation defects. Given this channel's involvement in other muscle disorders such as paramyotonia congenita and hyperkalemic periodic paralysis, our study exemplifies how variations within the same gene can give rise to multiple distinct dysfunctions and phenotypes, revealing residues important in basic channel function.

muscle chloride and sodium channels).They classically include Myotonia Congenita (MC), Paramyotonia Congenita (PC) and sodium channel myotonias (SCM). Recent data from electrophysiological and molecular biological studies led to a new classification of these disorders and they are now classified as Cl or Na channel diseases. The chloride channel disorders include autosomal-recessive MC (Becker’s of patients.Features of muscle dysfunction in DM1 are impaired ambulation, myotonia, muscle weakness and atrophy. A 2006 Cochrane review concluded there was not sufficient data to consider any treatment safe and effective for myotonia.Participants/populationMale and female eligible participants aged between 18 to 80 who had at least one of the following1) genetically definite myotonia congenita (MC) or paramyotonia

of neuromuscular disorders with variable onset, ranging from a rare form of congenital myasthenic syndrome to both hypokalemic and hyperkalemic forms of periodic paralysis and paramyotonia congenita. Here we report on 3 unrelated patients without family history presenting with recurrent, life-threatening episodes of laryngospasm from the first months of life. Clinical features more typically associated

* Carbonic anhydrase inhibitors * Show All * Follow-up * * * Prognosis * Patient Education * Show All * Questions & Answers * Tables * ReferencesFollow-up PrognosisSee the list below: * * Hyperkalemic periodic paralyses and paramyotonia congenita * * When not associated with weakness, these usually do not interfere with ability to work

, such as phosphorylation or second messengers. Most cases of hyperkalemic PP are due to 2 mutations in SCN4A, T704M, and M1592V. Mutations in the sodium channel, especially at residues 1448 and 1313, are responsible for paramyotonia congenita. A small proportion of hypokalemic periodic paralysis cases are associated with mutations at codons 669 and 672 (HypoPP2). In HypoPP2, sodium channel mutations enhance directly interact with PIP2 during normal gating. In Andersen-Tawil syndrome, there is decreased PIP2 affinity. In thyrotoxic PP, none of the mutations alters Kir2.6 rectification. [7] Previous Next: EpidemiologyFrequencyThe frequencies of hyperkalemic periodic paralysis, paramyotonia congenita (PC), and potassium-aggravated myotonias (PAM) are not known. Hypokalemic periodic paralysis has a prevalence

, such as phosphorylation or second messengers. Most cases of hyperkalemic PP are due to 2 mutations in SCN4A, T704M, and M1592V. Mutations in the sodium channel, especially at residues 1448 and 1313, are responsible for paramyotonia congenita. A small proportion of hypokalemic periodic paralysis cases are associated with mutations at codons 669 and 672 (HypoPP2). In HypoPP2, sodium channel mutations enhance directly interact with PIP2 during normal gating. In Andersen-Tawil syndrome, there is decreased PIP2 affinity. In thyrotoxic PP, none of the mutations alters Kir2.6 rectification. [7] Previous Next: EpidemiologyFrequencyThe frequencies of hyperkalemic periodic paralysis, paramyotonia congenita (PC), and potassium-aggravated myotonias (PAM) are not known. Hypokalemic periodic paralysis has a prevalence

are a group of rare genetic neuromuscular disorders caused by dysfunction of ion channels that are critical for muscle membrane excitability. The hallmark of these disorders is that symptoms occur in an episodic or paroxysmal fashion causing acute disability. The NDMs include myotonia congenita (MC), sodium channel myotonia (SMC) and paramyotonia congenita (PMC). They have a point prevalence in England

-1.21). Disease-specific prevalence figures were as follows: myotonia congenita 0.52/100,000 (95% CI 0.46-0.59), paramyotonia congenita 0.17/100,000 (95% CI 0.13-0.20), sodium channel myotonias 0.06/100,000 (95% CI 0.04-0.08), hyperkalemic periodic paralysis 0.17/100,000 (95% CI 0.13-0.20), hypokalemic periodic paralysis 0.13/100,000 (95% CI 0.10-0.17), and Andersen-Tawil syndrome (ATS) 0.08/100,000 (95% CI 0.05-0.10). In the whole sample (665 patients), 15 out of 104 different CLCN1 mutations accounted for 60% of all patients with myotonia congenita, 11 out of 22 SCN4A mutations for 86% of paramyotonia congenita/sodium channel myotonia pedigrees, and 3 out of 17 KCNJ2 mutations for 42% of ATS pedigrees. We describe for the first time the overall prevalence of genetically defined skeletal