Skeletal muscle Na+ channel disorders

Simkin, D. J.

doi:10.3389/fphar.2011.00063

Cited by 25 publications

(40 citation statements)

References 142 publications

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“…Dominant mutations usually lead to a gain of function of the Nav1.4 sodium channel, resulting in congenital myotonia or periodic paralysis, collectively known as sodium channelopathies [3]. These mutations in SCN4A can result in sustained muscle contraction, causing myotonia, or a prolonged refractory state with fast inactivation of the channel, yielding a periodic paralysis phenotype [4,5]. In rare cases recessive loss of function SCN4A mutations have been shown to cause a congenital myasthenic syndrome [3,6].…”

Section: Introductionmentioning

confidence: 99%

Congenital myopathy with “corona” fibres, selective muscle atrophy, and craniosynostosis associated with novel recessive mutations in SCN4A

Gonorazky

Marshall

Almurshed

et al. 2017

Neuromuscular Disorders

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We describe two brothers with lower facial weakness, highly arched palate, scaphocephaly due to synostosis of the sagittal and metopic sutures, axial hypotonia, proximal muscle weakness, and mild scoliosis. The muscle MRI of the younger sibling revealed a selective pattern of atrophy of the gluteus maximus, adductor magnus and soleus muscles. Muscle biopsy of the younger sibling revealed myofibres with internalized nuclei, myofibrillar disarray, and "corona" fibres. Both affected siblings were found to be compound heterozygous for c.3425G>A (p.Arg1142Gln) and c.1123T>C (p.Cys375Arg) mutations in SCN4A on exome sequencing, and the parents were confirmed carriers of one of the mutations. Electrophysiological characterization of the mutations revealed the Cys375Arg confers full and Arg1142Gln mild partial loss-of-function.Loss of function of the Nav1.4 channel leads to a decrement of the action potential and subsequent reduction of muscle contraction. The unusual muscle biopsy features suggest a more complex pathomechanism, and broaden the phenotype associated with SCN4A mutations. Gonorazky et al. 3

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Section: Introductionmentioning

confidence: 99%

Congenital myopathy with “corona” fibres, selective muscle atrophy, and craniosynostosis associated with novel recessive mutations in SCN4A

Gonorazky

Marshall

Almurshed

et al. 2017

Neuromuscular Disorders

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Section: Discussionmentioning

confidence: 99%

“…4 SCN4A encodes NaV1.4, a voltage-gated sodium channel prominently expressed at the neuromuscular junction of striated muscles, including laryngeal muscles. Clinically, SCN4A-related disorders include a wide range of phenotypes, 4 mainly hyperkalemic periodic paralysis (HYPP) and hypokalemic periodic paralysis, PAM, and PMC, with both distinct and overlapping features. SCN4A-related disorders usually present from childhood to adolescence with variable degrees of myotonia and periodic or fixed weakness, but early infantile presentations with features of a congenital myasthenic syndrome, 8 hypotonia, 7 or stridor 6 have been rarely recognized.…”

Section: Discussionmentioning

confidence: 99%

Mutations inSCN4A: A Rare but Treatable Cause of Recurrent Life-Threatening Laryngospasm

et al. 2014

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Laryngospasm is a rare but potentially life-threatening occurrence in infants and usually has infective, allergic, metabolic, or anatomic causes. Underlying genetic conditions are rarely considered. Mutations in SCN4A encoding the voltage-gated sodium channel NaV1.4 have been implicated in a wide spectrum 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 with SCN4A-related disorders such as generalized muscle hypertrophy with clinical or electrical myotonia evolved later in life. All patients were found to be heterozygous for the same SCN4A mutation, c.3917G>A; p.Gly1306Glu. Treatment with carbamazepine resulted in complete abolition of recurrent laryngospasm and alleviated symptoms associated with myotonia and muscle stiffness. We conclude that SCN4A mutations ought to be considered in the differential diagnosis of recurrent infantile laryngospasm because timely institution of treatment can be life-saving.

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“…In the 1990's, the term "channelopathy" was first coined to describe skeletal muscle hereditary diseases, including periodic paralysis and myotonia, due to mutations in the SCN4A gene encoding the muscle isoform of voltage-gated sodium channels (Wang et al, 1993). Many of these aspects are reviewed in this special issue dedicated to voltage-gated sodium channels (Simkin and Bendahhou, 2011;Savio-Galimberti et al, 2012).…”

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confidence: 99%

Recent advances in voltage-gated sodium channels, their pharmacology and related diseases

2013

Frontiers Research Topics

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Skeletal muscle Na+ channel disorders

Cited by 25 publications

References 142 publications

Congenital myopathy with “corona” fibres, selective muscle atrophy, and craniosynostosis associated with novel recessive mutations in SCN4A

Congenital myopathy with “corona” fibres, selective muscle atrophy, and craniosynostosis associated with novel recessive mutations in SCN4A

Mutations inSCN4A: A Rare but Treatable Cause of Recurrent Life-Threatening Laryngospasm

Recent advances in voltage-gated sodium channels, their pharmacology and related diseases

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