Painful cramps and giant myotonic discharges in a family with the Nav1.4‐G1306A mutation

Torbergsen, T.; Jurkat‐Rott, Karin; Stålberg, Erik; Løseth, Sissel; Hodneo, Anne; Lehmann‐Horn, Frank

doi:10.1002/mus.24672

Cited by 8 publications

(7 citation statements)

References 17 publications

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“…At present, no useful guidelines exist on how to clarify the cause of myalgia. 19 Painful cramps or myalgia with myotonia have been reported in a few families with other SCN4A mutations, 20–23 but to the best of our knowledge, myalgia without myotonic discharges on EMG has not been reported before. Besides p.A1156T SCN4A mutation, DM2 is an important disorder to be considered in differential diagnostics of myalgic syndromes.…”

Section: Discussionmentioning

confidence: 85%

Predominantly myalgic phenotype caused by the c.3466G>A p.A1156T mutation in SCN4A gene

et al. 2017

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Objective:To characterize the clinical phenotype in patients with p.A1156T sodium channel mutation.Methods:Twenty-nine Finnish patients identified with the c.3466G>A p.A1156T mutation in the SCN4A gene were extensively examined. In a subsequent study, 63 patients with similar myalgic phenotype and with negative results in myotonic dystrophy type 2 genetic screening (DM2-neg group) and 93 patients diagnosed with fibromyalgia were screened for the mutation. Functional consequences of the p.A1156T mutation were studied in HEK293 cells with whole-cell patch clamp.Results:The main clinical manifestation in p.A1156T patients was not myotonia or periodic paralysis but exercise- and cold-induced muscle cramps, muscle stiffness, and myalgia. EMG myotonic discharges were detected in most but not all. Electrophysiologic compound muscle action potentials exercise test showed variable results. The p.A1156T mutation was identified in one patient in the DM2-neg group but not in the fibromyalgia group, making a total of 30 patients so far identified. Functional studies of the p.A1156T mutation showed mild attenuation of channel fast inactivation.Conclusions:The unspecific symptoms of myalgia stiffness and exercise intolerance without clinical myotonia or periodic paralysis in p.A1156T patients make the diagnosis challenging. The symptoms of milder SCN4A mutations may be confused with other similar myalgic syndromes, including fibromyalgia and myotonic dystrophy type 2.

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Section: Discussionmentioning

confidence: 85%

Predominantly myalgic phenotype caused by the c.3466G>A p.A1156T mutation in SCN4A gene

et al. 2017

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“…Another explanation may be that SCN4A mutations have higher rates of myotonia than the next most prevalent gene mutation, CACNA1S, which can cause pain. 8,9 To understand the burden of pain on patients with PP, we compared our survey results with the general population. A study of 472 US subjects evaluated their pain using the WPI and SS scales and were separated into a group with chronic widespread pain, a group with clinically diagnosed fibromyalgia, and a control group.…”

Section: Discussionmentioning

confidence: 99%

“…Subgroup analysis revealed that half of the patients with an SCN4A mutation met the criteria for fibromyalgia, which may suggest some overlap between a predominantly myalgic phenotype 25 and the PP phenotype. Another explanation may be that SCN4A mutations have higher rates of myotonia than the next most prevalent gene mutation , CACNA1S, which can cause pain 8,9 …”

Section: Discussionmentioning

confidence: 99%

“…Additional case series document a predominantly myalgic phenotype of SCN4A point mutations, known to cause hyperkalemic and hypokalemic PP, which shares characteristics common to PP, such as exercise‐induced myotonia, muscle cramps, and a “warming‐up” phenomenon. However, none of patients described met the criteria for PP 8‐10 . More studies are needed to determine whether there is overlap of this myalgic phenotype with the SCN4A point mutations causing PP.…”

Section: Introductionmentioning

confidence: 98%

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Pain as a significant symptom in patients with periodic paralysis—A cross‐sectional survey

2021

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Introduction: Periodic paralysis (PP) is thought to be limited to episodes of muscle weakness, but there are reports of fibromyalgia-like pain in PP. We aimed to evaluate pain and comorbid sleep, fatigue, and mood disorders in PP patients. Methods: We administered a cross-sectional survey to PP patients at the 2019 Periodic Paralysis Conference. The survey consisted of the Brief Pain Inventory, Widespread Pain Index, Pittsburgh Sleep Quality Index, Modified Fatigue Impact Scale, and ten-question Center for Epidemiologic Studies Depression Scale (CESD-10).Descriptive statistics for PP patients were calculated and compared with earlier studies.Results: Forty-four individuals with PP took the survey. Of these patients, 52.3% reported a moderate to severe interference of pain on their lives, and 45.5% met the study criteria for fibromyalgia. Patients with SCN4A mutations had higher rates of fibromyalgia than the next most prevalent gene mutation, CACNA1S. In patients with pain, there were increased rates of comorbid fatigue, depression, and poor sleep quality.Discussion: Pain, akin to fibromyalgia, is a significant symptom of PP and can affect quality of life. Pain in PP was more prevalent than in the general population, at a rate comparable with other chronic neuromuscular disease groups. PP patients could benefit from a multidisciplinary approach to assess their pain, sleep, fatigue, and mood.

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“…(n = 1), SNEL, dies at 20 months from cardiorespiratory arrest p.Phe1298Cys (c.3893T>G) [65] USE with MEX (400 mg) (n = 1), moderate improvement p.Gly1306Ala (c.3917G>C) [33] positive to MEX (600 mg) (n = 2) [66] NR to MEX, ACZ, and CBZ (nd) (n = 1) p.Gly1306Glu (c.3917G>A) [67] NR to MEX (720 mg), oxcarbazepine (nd), and thiazide diuretics (nd), positive to ACZ (500 mg)…”

Section: Randomized Clinical Trials (Class Of Evidence I)mentioning

confidence: 99%

Targeted Therapies for Skeletal Muscle Ion Channelopathies: Systematic Review and Steps Towards Precision Medicine

Desaphy

Altamura

Vicart

et al. 2021

JND

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Background: Skeletal muscle ion channelopathies include non-dystrophic myotonias (NDM), periodic paralyses (PP), congenital myasthenic syndrome, and recently identified congenital myopathies. The treatment of these diseases is mainly symptomatic, aimed at reducing muscle excitability in NDM or modifying triggers of attacks in PP. Objective: This systematic review collected the evidences regarding effects of pharmacological treatment on muscle ion channelopathies, focusing on the possible link between treatments and genetic background. Methods: We searched databases for randomized clinical trials (RCT) and other human studies reporting pharmacological treatments. Preclinical studies were considered to gain further information regarding mutation-dependent drug effects. All steps were performed by two independent investigators, while two others critically reviewed the entire process. Results: For NMD, RCT showed therapeutic benefits of mexiletine and lamotrigine, while other human studies suggest some efficacy of various sodium channel blockers and of the carbonic anhydrase inhibitor (CAI) acetazolamide. Preclinical studies suggest that mutations may alter sensitivity of the channel to sodium channel blockers in vitro, which has been translated to humans in some cases. For hyperkalemic and hypokalemic PP, RCT showed efficacy of the CAI dichlorphenamide in preventing paralysis. However, hypokalemic PP patients carrying sodium channel mutations may have fewer benefits from DCP compared to those carrying calcium channel mutations. Few data are available for treatment of congenital myopathies. Conclusions: These studies provided limited information about the response to treatments of individual mutations or groups of mutations. A major effort is needed to perform human studies for designing a mutation-driven precision medicine in muscle ion channelopathies.

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Painful cramps and giant myotonic discharges in a family with the Nav1.4‐G1306A mutation

Abstract: Ephaptic transmission between neighboring muscle fibers may not only cause the unusual size of the myotonic discharges in this family, but also a more severe type of potassium-aggravated myotonia than myotonia fluctuans.

Cited by 8 publications

References 17 publications

Predominantly myalgic phenotype caused by the c.3466G>A p.A1156T mutation in SCN4A gene

Predominantly myalgic phenotype caused by the c.3466G>A p.A1156T mutation in SCN4A gene

Pain as a significant symptom in patients with periodic paralysis—A cross‐sectional survey

Targeted Therapies for Skeletal Muscle Ion Channelopathies: Systematic Review and Steps Towards Precision Medicine

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