Phenotypic variability in childhood of skeletal muscle sodium channelopathies.
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.


METHODS
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.


CONCLUSIONS
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.
Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. Electronic address: magenta@md.okayama-u.ac.jp.
Harumi
H
Yoshinaga
Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Shunichi
S
Sakoda
Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Takashi
T
Shibata
Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Tomoyuki
T
Akiyama
Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Makio
M
Oka
Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Jun-Hui
JH
Yuan
Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Hiroshi
H
Takashima
Department of Neurology, Osaka University Graduate School of Medicine, Osaka, Japan.
Masanori P
MP
Takahashi
Department of Pediatrics, Nipponkokan Fukuyama Hospital, Hiroshima, Japan.
Tetsuro
T
Kitamura
Department of Pediatrics, Nipponkokan Fukuyama Hospital, Hiroshima, Japan.
Nagako
N
Murakami
Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Katsuhiro
K
Kobayashi
D000200:Action Potentials / Q000235:genetics; D000293:Adolescent; D053447:Channelopathies / Q000235:genetics* / Q000473:pathology*; D002648:Child; D003402:Creatine Kinase; D004252:DNA Mutational Analysis; D004576:Electromyography; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D008958:Models, Molecular; D018482:Muscle, Skeletal / Q000473:pathology*; D009154:Mutation / Q000235:genetics*; D062553:NAV1.4 Voltage-Gated Sodium Channel / Q000235:genetics*; D010641:Phenotype
D062553:NAV1.4 Voltage-Gated Sodium Channel; C106251:SCN4A protein, human; D003402:Creatine Kinase
SCN4A; electromyography; genetic testing; mutation; myotonia; periodic paralysis; sodium channelopathy