Abstract
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 language | English |
|---|---|
| Pages (from-to) | 504-508 |
| Number of pages | 5 |
| Journal | Pediatric Neurology |
| Volume | 52 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 1 2015 |
Fingerprint
Keywords
- electromyography
- genetic testing
- mutation
- myotonia
- periodic paralysis
- SCN4A
- sodium channelopathy
ASJC Scopus subject areas
- Clinical Neurology
- Pediatrics, Perinatology, and Child Health
- Developmental Neuroscience
- Neurology
- Medicine(all)
Cite this
Phenotypic Variability in Childhood of Skeletal Muscle Sodium Channelopathies. / Yoshinaga, Harumi; Sakoda, Shunichi; Shibata, Takashi; Akiyama, Tomoyuki; Oka, Makio; Yuan, Jun Hui; Takashima, Hiroshi; Takahashi, Masanori P.; Kitamura, Tetsuro; Murakami, Nagako; Kobayashi, Katsuhiro.
In: Pediatric Neurology, Vol. 52, No. 5, 01.05.2015, p. 504-508.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Phenotypic Variability in Childhood of Skeletal Muscle Sodium Channelopathies
AU - Yoshinaga, Harumi
AU - Sakoda, Shunichi
AU - Shibata, Takashi
AU - Akiyama, Tomoyuki
AU - Oka, Makio
AU - Yuan, Jun Hui
AU - Takashima, Hiroshi
AU - Takahashi, Masanori P.
AU - Kitamura, Tetsuro
AU - Murakami, Nagako
AU - Kobayashi, Katsuhiro
PY - 2015/5/1
Y1 - 2015/5/1
N2 - 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.
AB - 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.
KW - electromyography
KW - genetic testing
KW - mutation
KW - myotonia
KW - periodic paralysis
KW - SCN4A
KW - sodium channelopathy
UR - http://www.scopus.com/inward/record.url?scp=84951567391&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84951567391&partnerID=8YFLogxK
U2 - 10.1016/j.pediatrneurol.2015.01.014
DO - 10.1016/j.pediatrneurol.2015.01.014
M3 - Article
C2 - 25724373
AN - SCOPUS:84951567391
VL - 52
SP - 504
EP - 508
JO - Pediatric Neurology
JF - Pediatric Neurology
SN - 0887-8994
IS - 5
ER -