1/9. Novel mutations in families with unusual and variable disorders of the skeletal muscle sodium channel.Mutations in the skeletal muscle sodium channel gene (SCN4A) have been described in paramyotonia congenita (PMC) and hyperkalaemic periodic paralysis (HPP). We have found two mutations in SCN4A which affect regions of the sodium channel not previously associated with a disease phenotype. Furthermore, affected family members display an unusual mixture of clinical features reminiscent of PMC, HPP and of a third disorder, myotonia congenita (MC). The highly variable individual expression of these symptoms, including in some cases apparent non-penetrance, implies the existence of modifying factors. Mutations in SCN4A can produce a broad range of phenotypes in muscle diseases characterized by episodic abnormalities of membrane excitability.- - - - - - - - - - ranking = 1keywords = paramyotonia congenita, paramyotonia, myotonia, congenita (Clic here for more details about this article) |
2/9. Hyperkalaemic periodic paralysis and anaesthesia.Hyperkalaemic periodic paralysis is the rarer of the two forms of potassium-associated familial paralysis. We report a family with hyperkalaemic periodic paralysis with paramyotonia and the anaesthetic management of four affected members. In three of these, paralytic episodes had been precipitated by previous anaesthesia, but this was avoided in the anaesthetics described. We conclude from our experiences that with depletion of potassium before surgery, prevention of carbohydrate depletion, avoidance of potassium-releasing anaesthetic drugs and maintenance of normothermia, patients with hyperkalaemic periodic paralysis can be anaesthetised without complications. We have no evidence that they exhibit abnormal sensitivity to nondepolarising neuromuscular relaxants.- - - - - - - - - - ranking = 0.27052505523793keywords = paramyotonia, myotonia (Clic here for more details about this article) |
3/9. Paramyotonia congenita or hyperkalemic periodic paralysis? Clinical and electrophysiological features of each entity in one family.The nosological distinction between paramyotonia congenita (PC) and hyperkalemic periodic paralysis (HPP) continues to generate debate. Recently, electrophysiological signs thought to be specific for each entity have been described and have been used to bolster the argument that the two disorders are distinct. We report a particularly instructive family wherein individual members had clinical features of either PC or HPP and electrophysiological features of both. We suggest that PC and HPP represent part of the spectrum of a single genetic disorder. Evoked response testing, with exercise and cold provocation, may be useful in determining the physiologic pattern that predominates in any one individual.- - - - - - - - - - ranking = 1.0095436537406keywords = paramyotonia congenita, paramyotonia, myotonia, congenita (Clic here for more details about this article) |
4/9. Adynamia episodica hereditaria: what causes the weakness?The cause of weakness was investigated in a patient with adynamia episodica hereditaria without myotonia. A pattern of exercise and rest produced episodes of hyperkalemic periodic paralysis. In addition, local muscle weakness was induced by forearm cooling. Investigations on isolated intercostal muscle demonstrated that a high potassium concentration in the bathing solution triggered a noninactivating membrane current causing depolarization of the muscle fibers. This current was carried by sodium as it could be inhibited by tetrodotoxin. The abnormal sodium conductance led to an increase of sodium within the fibers. This was demonstrated directly by intracellular recordings. Weakness induced by rest after exercise and cold-induced weakness appeared to have different pathomechanisms. In the cold, the muscle fibers retained a normal resting potential, but their excitability was reduced and their mechanical threshold was increased. These findings also provide evidence that the mechanism of cold-induced weakness in adynamia episodica is distinctly different from the cold-induced weakness that occurs in paramyotonia congenita.- - - - - - - - - - ranking = 0.9995377602481keywords = paramyotonia congenita, paramyotonia, myotonia, congenita (Clic here for more details about this article) |
5/9. Lack of cold sensitivity in hyperkalemic periodic paralysis.The nosologic distinction between paramyotonia congenita and hyperkalemic periodic paralysis is somewhat blurred. Muscle membrane inexcitability induced by cooling seems to be characteristic of paramyotonia congenita. The effect of cooling on the maximal compound muscle action potential (CMAP) in patients with paramyotonia congenita was compared to that in patients with hyperkalemic periodic paralysis. Diminution in CMAP amplitude and area, which was observed in paramyotonia congenita, did not occur in hyperkalemic periodic paralysis. We suggest that this effect of cooling on the CMAP can be utilized in the differentiation of these two syndromes.- - - - - - - - - - ranking = 3.9872751283458keywords = paramyotonia congenita, paramyotonia, myotonia, congenita (Clic here for more details about this article) |
6/9. hypokalemic periodic paralysis: in vitro investigation of muscle fiber membrane parameters.To study the mechanism of attacks in familial hypokalemic paralysis, we recorded resting membrane potentials, action potentials, current-voltage relationships, and isometric forces in intercostal muscle fibers from three patients. In normal extracellular medium, the resting potential was reduced, but membrane conductance was not different from control. Excitability was reduced and the action potentials had no overshoot. On exposure to a 1-mM potassium solution, with or without insulin, the cells depolarized to about -50 mV, and became inexcitable. Over the tested membrane potential range from -120 to -40 mV, the slope conductance in the 1-mM potassium solution was not different from that of control fibers in a 1-mM potassium solution. In particular, the potassium component conductance was not reduced. Depolarized fibers could not be completely repolarized by returning to a 3.5-mM potassium solution. An experimentally induced transient shift of the chloride equilibrium potential to a highly negative value caused stable repolarization. Paralysis could also be induced by replacement of extracellular chloride with an impermanent anion, a treatment which causes myotonia in healthy fibers. It was concluded that the basic defects are a reduced excitability and an increased sodium conductance, and that these defects are aggravated on reduction of the extracellular potassium concentration.- - - - - - - - - - ranking = 0.0027189781616502keywords = myotonia (Clic here for more details about this article) |
7/9. Molecular genetic and genetic correlations in sodium channelopathies: lack of founder effect and evidence for a second gene.We present a correlation of molecular genetic data (mutations) and genetic data (dinucleotide-repeat polymorphisms) for a cohort of seven hyperkalemic periodic paralysis (HyperPP) and two paramyotonia congenita (PC) families from diverse ethnic backgrounds. We found that each of three previously identified point mutations of the adult skeletal muscle sodium-channel gene occurred on two different dinucleotide-repeat haplotypes. These results indicate that dinucleotide-repeat haplotypes are not predictive of allelic heterogeneity in sodium channelopathies, contrary to previous suggestions. In addition, we identified a HyperPP pedigree in which the dominant disorder was not linked to the sodium-channel gene. Thus, a second locus can give rise to a similar clinical phenotype. Some individuals in this pedigree exhibited a base change causing the nonconservative substitution of an evolutionarily conserved amino acid. Because this change was not present in 240 normal chromosomes and was near another HyperPP mutation, is fulfilled the most commonly used criteria for being a mutation rather than a polymorphism. However, linkage studies using single-strand conformation polymorphism-derived and sequence-derived haplotypes excluded this base change as a causative mutation: these data serve as a cautionary example of potential pitfalls in the delineation of change-of-function point mutations.- - - - - - - - - - ranking = 0.99681878208645keywords = paramyotonia congenita, paramyotonia, myotonia, congenita (Clic here for more details about this article) |
8/9. A proposed mutation, Val781Ile, associated with hyperkalemic periodic paralysis and cardiac dysrhythmia is a benign polymorphism.Twenty different point mutations have been identified in the gene coding for the alpha subunit of the adult skeletal muscle sodium channel in families with hyperkalemic periodic paralysis, paramyotonia congenita, and the potassium-aggravated myotonias. One novel mutation (Val(781)Ile) was reported in an adopted boy with potassium-sensitive weakness and cardiac dysrhythmia. The confidence in establishing this rare amino acid substitution as a causative mutation was limited by the absence of family members for segregation analysis. Functional expression studies herein show that Val(781)Ile is most likely a benign polymorphism and not a disease-associated mutation.- - - - - - - - - - ranking = 0.9995377602481keywords = paramyotonia congenita, paramyotonia, myotonia, congenita (Clic here for more details about this article) |
9/9. fibromyalgia in hyperkalemic periodic paralysis.A 43-year-old woman presented at the age of 38 with joint pains and muscle stiffness. Tender points were found fulfilling ACR criteria (1) for fibromyalgia. She had well developed muscles and decreasing muscle power since the age of 35. Muscle pains increased after exercise. Her 10-year-old son had similar symptoms and one paralytic attack. Muscle pain and fatigue increasing with age were found by history in three close relatives. forearm cold water test produced myotonia in both mother and son. electromyography was normal and muscle biopsy showed minor unspecific changes. Biochemical investigation of muscle mitochondrial function was normal. Peroral potassium load test produced complete muscle paralysis at a potassium serum level of 5.0 mmol/l. Autosomal dominant hyperkalemic periodic paralysis was diagnosed. Frequent carbohydrate enriched meals, peroral bendroflumethiazide and restriction to submaximal exercise improved muscle and joint pain. Salbutamol peroral spray relieved the periodic weakness.- - - - - - - - - - ranking = 0.0027189781616502keywords = myotonia (Clic here for more details about this article) |