Mutations of the SCN1A gene in acute encephalopathy.
OBJECTIVE
Acute encephalopathy is the most serious complication of pediatric viral infections, such as influenza and exanthema subitum. It occurs worldwide, but is most prevalent in East Asia. Recently, there have been sporadic case reports of epilepsy/febrile seizure and acute encephalopathy with a neuronal sodium channel alpha 1 subunit (SCN1A) mutation. To determine whether SCN1A mutations are a predisposing factor of acute encephalopathy, we sought to identify SCN1A mutations in a large case series of acute encephalopathy including various syndromes.


METHODS
We analyzed the SCN1A gene in 87 patients with acute encephalopathy, consisting of 20 with acute necrotizing encephalopathy (ANE), 61 with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), and six with nonspecific (unclassified) acute encephalopathy.


RESULTS
Three patients had distinct point mutations. Two of them had epileptic seizures prior to acute encephalopathy. Clinical and neuroradiologic findings of acute encephalopathy were diverse among the three patients, although all had a prolonged and generalized seizure at its onset. The first patient with V982L had partial epilepsy and AESD. The second patient with M1977L had febrile seizures and nonspecific acute encephalopathy. The third patient with R1575C had no seizures until the onset of ANE. M1977L was a novel mutation, whereas the remaining two, V982L and R1575C, have previously been reported in cases of Dravet syndrome and acute encephalopathy, respectively.


CONCLUSIONS
These findings provide further evidence that SCN1A mutations are a predisposing factor for the onset of various types of acute encephalopathy.
Department of Developmental Medical Sciences, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. makisaito-tky@umin.net.jp
Makiko
M
Saitoh
Mayu
M
Shinohara
Hideki
H
Hoshino
Masaya
M
Kubota
Kaoru
K
Amemiya
Jun-Lchi
JL
Takanashi
Su-Kyeong
SK
Hwang
Shinichi
S
Hirose
Masashi
M
Mizuguchi
D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D018792:Encephalitis, Viral / Q000150:complications / Q000235:genetics*; D004827:Epilepsy / Q000150:complications / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D007223:Infant; D007564:Japan / Q000453:epidemiology; D004684:Leukoencephalitis, Acute Hemorrhagic / Q000209:etiology / Q000235:genetics; D008297:Male; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics*; D015222:Sodium Channels / Q000235:genetics*
D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; D015222:Sodium Channels