A patient with mutation in the <i>SCN4A</i>
 p.M1592v presenting with fixed weakness, rhabdomyolysis, and episodic worsening of weakness

Lee, Eric; Chahin, Nizar

doi:10.1002/mus.23803

Cited by 7 publications

(5 citation statements)

References 4 publications

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“…Segregation analysis confirmed the presence of the pathogenic mutation in the patient’s affected father. Mutations of the gene SCN4A lead to a skeletal muscle channelopathy with variable clinical presentation, including myotonia, episodic hypokalemic paralysis, and rhabdomyolysis in rare cases [17]. In patient AN21, we identified a previously reported pathogenic mutation in MYH3 (Table 2) [12].…”

Section: Resultsmentioning

confidence: 99%

“…The gene SCN4A encodes the α-subunit of the skeletal muscle voltage-dependent sodium channel type 4, and mutations in SCN4A lead to a skeletal muscle channelopathy with variable clinical presentation, including myotonia, episodic hypokalemic paralysis, and rhabdomyolysis in rare cases [17]. Interestingly, mutations in MYH3 usually lead to a rare and severe form of arthrogryposis and myopathy also known as Freeman-Sheldon/Sheldon-Hall syndrome [12].…”

Section: Discussionmentioning

confidence: 99%

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Exome sequencing in Jewish and Arab patients with rhabdomyolysis reveals single-gene etiology in 43% of cases

et al. 2017

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Background Rhabdomyolysis is a clinical emergency that may cause acute kidney injury (AKI). It can be acquired or due to monogenic mutations. Around 60 different rare monogenic forms of rhabdomyolysis have been reported to date. In the clinical setting, identifying the underlying molecular diagnosis is challenging, due to nonspecific presentation, the high number of causative genes, and current lack of data on the prevalence of monogenic forms. Methods We employed whole exome sequencing (WES) to reveal the percentage of rhabdomyolysis cases explained by single-gene (monogenic) mutations in one of 58 candidate genes. We investigated a cohort of 21 unrelated families with rhabdomyolysis. in whom no underlying etiology had been previously established. Results Using WES, we identified causative mutations in candidate genes in nine of the 21 families (43%). We detected disease-causing mutations in eight of 58 candidate genes, grouped into the following categories: 1) disorders of fatty acid metabolism (CPT2), 2) disorders of glycogen metabolism (PFKM and PGAM2), 3) disorders of abnormal skeletal muscle relaxation and contraction (CACNA1S, MYH3, RYR1 and SCN4A), and 4) disorders of purine metabolism (AHCY). Conclusions Our findings demonstrate a very high detection rate for monogenic etiologies using WES and reveal broad genetic heterogeneity for rhabdomyolysis. These results highlight the importance of molecular genetic diagnostics for establishing an etiologic diagnosis. Because these patients are at risk for recurrent episodes of rhabdomyolysis and subsequent risk for AKI, WES allows adequate prophylaxis and treatment for these patients and their family members and enables a personalized medicine approach.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Exome sequencing in Jewish and Arab patients with rhabdomyolysis reveals single-gene etiology in 43% of cases

et al. 2017

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“…SCN4A gene mutation was recently discovered in an 8 year-old girl with recurrent rhabdomyolysis triggered by emotional stress, exercise, and infection 196 . Baseline CK levels between the attacks were normal or mildly elevated.…”

Section: Genetic Causes Of Rhabdomyolysismentioning

confidence: 99%

Diagnostic evaluation of rhabdomyolysis

2015

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Rhabdomyolysis is characterized by severe acute muscle injury resulting in muscle pain, weakness, and/or swelling with release of myofiber contents into the bloodstream. Symptoms develop over hours to days following an inciting factor and may be associated with dark pigmentation of the urine. Serum creatine kinase and urine myoglobin levels are markedly elevated. The clinical examination, history, laboratory studies, muscle biopsy, and genetic testing are useful tools for diagnosis of rhabdomyolysis, and they can help differentiate acquired from inherited causes of rhabdomyolysis. Acquired causes include substance abuse, medication or toxic exposures, electrolyte abnormalities, endocrine disturbance, and autoimmune myopathies. Inherited predisposition to rhabdomyolysis can occur with disorders of glycogen metabolism, fatty acid beta-oxidation, and mitochondrial oxidative phosphorylation. Less common inherited causes of rhabdomyolysis include structural myopathies, channelopathies, and sickle cell disease. This review focuses on the differentiation of acquired and inherited causes of rhabdomyolysis and proposes a practical diagnostic algorithm.

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“…Notably, mutations were enriched at exons 12, 13, and 24 of the SCN4A gene, leading to amino acid substitutions including T704M, M1592V, V781I, R675G, R675W, R675Q, and R1129Q ( 2 – 5 ). To the best of our knowledge, NormoKPP associated with the p.M1592V mutation has been reported in only three pedigrees ( 3 , 6 , 7 ). In this study, we report a familial NormoKPP associated with the SCN4A p.M1592V mutation, and reviewed the literature.…”

Section: Introductionmentioning

confidence: 95%

Familial Normokalemic Periodic Paralysis Associated With Mutation in the SCN4A p.M1592V

Wang

et al. 2018

Front. Neurol.

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Periodic paralysis (PP) is an uncommon inherited disorder causing recurrent episodes of muscle weakness, with an incidence of 0.001%. Normokalemic periodic paralysis (NormoKPP) as the rarest subtype of PP contains both familial and sporadic. Familial NormoKPP caused by the p.M1592V mutation of the skeletal muscle sodium channel alpha subunit (SCN4A) gene is rarely reported. Only three pedigrees of NormoKPP related to mutations in the SCN4A p.M1592V have been previously reported. We herein presented a family case of NormoKPP associated with the SCN4A p.M1592V mutation, in which respiratory muscle paralysis occurred in the proband while not in his children. Moreover, we conducted a thorough literature review. To our knowledge, this is the first report of respiratory muscle paralysis as a symptom of NormoKPP associated with mutation in the SCN4A p.M1592V.

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A patient with mutation in the SCN4A p.M1592v presenting with fixed weakness, rhabdomyolysis, and episodic worsening of weakness

Cited by 7 publications

References 4 publications

Exome sequencing in Jewish and Arab patients with rhabdomyolysis reveals single-gene etiology in 43% of cases

Exome sequencing in Jewish and Arab patients with rhabdomyolysis reveals single-gene etiology in 43% of cases

Diagnostic evaluation of rhabdomyolysis

Familial Normokalemic Periodic Paralysis Associated With Mutation in the SCN4A p.M1592V

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