Phenotypic Variability in Childhood of Skeletal Muscle Sodium Channelopathies

Harumi Yoshinaga, Shunichi Sakoda, Takashi Shibata, Tomoyuki Akiyama, Makio Oka, Jun Hui Yuan, Hiroshi Takashima, Masanori P. Takahashi, Tetsuro Kitamura, Nagako Murakami, Katsuhiro Kobayashi

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


Background Mutations of the SCN4A gene cause several skeletal muscle channelopathies and overlapping forms of these disorders. However, the variability of the clinical presentation in childhood is confusing and not fully understood among pediatric neurologists. Patients We found three different mutations (p.V445M, p.I693L, and a novel mutation, p.V1149L) in SCN4A but not in the CLCN1 gene. The patient with p.V445M showed the clinical phenotype of sodium channel myotonia, but her clear symptoms did not appear until 11 years of age. Her younger sister and mother, who have the same mutation, displayed marked intrafamilial phenotypic heterogeneity from mild to severe painful myotonia with persistent weakness. The patient with p.I693L exhibited various symptoms that evolved with age, including apneic episodes, tonic muscular contractions during sleep, fluctuating severe episodic myotonia, and finally episodic paralyses. The patient with the novel p.V1149L mutation exhibited episodic paralyses starting at 3 years of age, and myotonic discharges were detected at 11 years of age for the first time. Conclusion The present cohort reveals the complexity, variability, and overlapping nature of the clinical features of skeletal muscle sodium channelopathies. These are basically treatable disorders, so it is essential to consider genetic testing before the full development of a patient's condition.

Original languageEnglish
Pages (from-to)504-508
Number of pages5
JournalPediatric Neurology
Issue number5
Publication statusPublished - May 1 2015


  • SCN4A
  • electromyography
  • genetic testing
  • mutation
  • myotonia
  • periodic paralysis
  • sodium channelopathy

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Neurology
  • Developmental Neuroscience
  • Clinical Neurology


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