title: A novel mutation in SCN4A causes severe myotonia and school-age-onset paralytic episodes.
abstract: Mutations in the pore-forming subunit of the skeletal muscle sodium channel (SCN4A) are responsible for hyperkalemic periodic paralysis, paramyotonia congenita and sodium channel myotonia. These disorders are classified based on their cardinal symptoms, myotonia and/or paralysis. We report the case of a Japanese boy with a novel mutation of SCN4A, p.I693L, who exhibited severe episodic myotonia from infancy and later onset mild paralytic attack. He started to have apneic episodes with generalized hypertonia at age of 11 months, then developed severe episodic myotonia since 2 years of age. He presented characteristic generalized features which resembled Schwarz-Jampel syndrome. After 7 years old, paralytic episodes occurred several times a year. The compound muscle action potential did not change during short and long exercise tests. Functional analysis of the mutant channel expressed in cultured cell revealed enhancement of the activation and disruption of the slow inactivation, which were consistent with myotonia and paralytic attack. The severe clinical features in his infancy may correspond to myotonia permanence, however, he subsequently experienced paralytic attacks. This case provides an example of the complexity and overlap of the clinical features of sodium channel myotonic disorders.
authors.affiliation: Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan. magenta@md.okayama-u.ac.jp
authors.forename: Harumi
authors.initials: H
authors.lastname: Yoshinaga
authors.forename: Shunichi
authors.initials: S
authors.lastname: Sakoda
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Good
authors.forename: Masanori P
authors.initials: MP
authors.lastname: Takahashi
authors.forename: Tomoya
authors.initials: T
authors.lastname: Kubota
authors.forename: Eri
authors.initials: E
authors.lastname: Arikawa-Hirasawa
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Nakata
authors.forename: Kinji
authors.initials: K
authors.lastname: Ohno
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Kitamura
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ohtsuka
mesh_terms: D002648:Child; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D009222:Myotonia / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D062553:NAV1.4 Voltage-Gated Sodium Channel / Q000235:genetics*; D010243:Paralysis / Q000150:complications / Q000175:diagnosis* / Q000235:genetics*; D012720:Severity of Illness Index
chemical_list: D062553:NAV1.4 Voltage-Gated Sodium Channel; C106251:SCN4A protein, human