Prolonged attacks of weakness with hypokalemia in <i>SCN4A</i>‐related paramyotonia congenita

Osch, Tim van; Stunnenberg, Bas C.; Sternberg, Damien; Kerklaan, Bertjan J.

doi:10.1002/mus.26190

Cited by 6 publications

(2 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have found a few reports on the overlap of PMC and HypoPP [19,20]. However, there is still no further electrophysiological function verification [21,22]. In the second case, we conclude that the R1448H mutation is the disease-causing mutation that leads to the overlap of PMC and HypoPP.…”

Section: Na V 14 Channel Introduction and Mechanisms Of Mutation In Scn4amentioning

confidence: 68%

Overlap of periodic paralysis and paramyotonia congenita caused by SCN4A gene mutations two family reports and literature review

et al. 2019

View full text Add to dashboard Cite

Objective : To verify the diagnosis of channelopathies in two families and explore the mechanism of the overlap between periodic paralysis (PP) and paramyotonia congenita (PMC). Methods : We have studied two cases with overlapping symptoms of episodic weakness and stiffness in our clinical center using a series of assessment including detailed medical history, careful physical examination, laboratory analyses, muscle biopsy, electrophysiological evaluation, and genetic analysis. Results : The first proband and part of his family with the overlap of PMC and hyperkalemic periodic paralysis (HyperPP) has been identified as c.2111C > T (T704M) substitution of the gene SCN4A . The second proband and part of his family with the overlap of PMC and hypokalemic periodic paralysis type 2 (HypoPP2) has been identified as c.4343G > A (R1448H) substitution of the gene SCN4A . In addition, one member of the second family with overlapping symptoms has been identified as a novel mutation c.2111C > T without the mutation c.4343G > A. Conclusions : SCN4A gene mutations can cause the overlap of PMC and PP (especially the HypoPP2). The clinical symptoms of episodic weakness and stiffness could happen at a different time or temperature. Based on diagnosis assessments such as medical history and muscle biopsy, further evaluations on long-time exercise test, genetic analysis, and patch clamp electrophysiology test need to be done in order to verify the specific subtype of channelopathies. Furthermore, the improvement of one member in the pregnancy period can be used as a reference for the other female in the child-bearing period with T704M.

show abstract

Section: Na V 14 Channel Introduction and Mechanisms Of Mutation In Scn4amentioning

confidence: 68%

Overlap of periodic paralysis and paramyotonia congenita caused by SCN4A gene mutations two family reports and literature review

et al. 2019

View full text Add to dashboard Cite

show abstract

“…[80] NR to ACZ (500 mg), PR to MEX (400 mg) (n = 1) [81] positive to PYR (180 mg) and PHE (300 mg) (n = 1), PYR resolved exercise-induced weakness and PHE reduced cold-induced stiffness [36] positive to RAN (2,000 mg) (n = 3) [82] PR and USE with ACZ (500 mg) (n = 1), PMC with HypoPP p.Ile1462Met (c.4386C>G) [36] positive to RAN (2,000 mg) Step-Stair test, the short form (SF-36) questionnaire, the creatine kinase level, and the use of escape medication (mexiletine). At the end, 5 participants were excluded from analysis due to loss of follow-up; notably, 1 patient developed reversible allergic reaction to lamotrigine.…”

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

View full text Add to dashboard Cite

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.

show abstract

The etiology of rhabdomyolysis: an interaction between genetic susceptibility and external triggers

Kruijt

Bersselaar

Kamsteeg

et al. 2020

Euro J of Neurology

View full text Add to dashboard Cite

Background and purposeRhabdomyolysis is a medical emergency characterized by acute skeletal muscle breakdown with a sudden rise and subsequent fall of serum creatine kinase (CK) levels. Rhabdomyolysis events are provoked by exposure to external triggers, possibly in combination with an increased genetic susceptibility. We aimed to describe comprehensively the external triggers and potentially pathogenic genetic variants possibly implicated in increased rhabdomyolysis susceptibility.MethodsWe performed a retrospective single‐center study, including a total of 1302 patients with an acute CK level exceeding 2000 IU/l.ResultsAnoxia was the most frequently reported trigger (40%). A subset of 193 patients were clinically suspected of an underlying genetic disorder (recurrent episodes, a positive family history, very high or persistently increased CK levels). In 72 of these patients, an unequivocal genetic defect was identified. A total of 22 genes with pathogenic variants were identified, including 52 different variants. Of those, 11 genes have been previously associated with rhabdomyolysis (ACADVL, ANO5, CPT2, DMD, DYSF, FKRP, HADHA, PGM1, LPIN1, PYGM, RYR1). Eleven genes are probably implicated in increased susceptibility (including AGL, CAPN3, CNBP, DMPK, MAGT1, ACADM, SCN4A, SGCA, SGCG, SMPD1, TANGO2).ConclusionThese findings suggest that the spectrum of genetic susceptibility for rhabdomyolysis has not yet been completely clarified. With the increasing availability of next‐generation sequencing in a diagnostic setting, we expect that in more cases a genetic defect will be identified.

show abstract

Prolonged attacks of weakness with hypokalemia in SCN4A‐related paramyotonia congenita

Cited by 6 publications

References 14 publications

Overlap of periodic paralysis and paramyotonia congenita caused by SCN4A gene mutations two family reports and literature review

Overlap of periodic paralysis and paramyotonia congenita caused by SCN4A gene mutations two family reports and literature review

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

The etiology of rhabdomyolysis: an interaction between genetic susceptibility and external triggers

Contact Info

Product

Resources

About