Journal
EPILEPSIA
Volume 55, Issue 7, Pages 994-1000Publisher
WILEY-BLACKWELL
DOI: 10.1111/epi.12668
Keywords
SCN8A; De novo mutation; Early onset epileptic encephalopathies
Categories
Funding
- Ministry of Health, Labour and Welfare of JapanJapan Society for the Promotion of Science [25293085, 25293235, 13313587, 24591500]
- Takeda Science Foundation
- Japan Science and Technology Agency
- Strategic Research Program for Brain Sciences [11105137]
- Ministry of Education, Culture, Sports, Science and Technology of Japan [12024421]
- Grants-in-Aid for Scientific Research [25293235, 22129005, 24591500, 24118001, 25293085] Funding Source: KAKEN
Ask authors/readers for more resources
Objective: De novo SCN8A mutations have been reported in patients with epileptic encephalopathy. Herein we report seven patients with de novo heterozygous SCN8A mutations, which were found in our comprehensive genetic analysis (target capture or whole-exome sequencing) for early onset epileptic encephalopathies (EOEEs). Methods: A total of 163 patients with EOEEs without mutations in known genes, including 6 with malignant migrating partial seizures in infancy (MMPSI), and 60 with unclassified EOEEs, were analyzed by target capture (28 samples) or whole-exome sequencing (135 samples). Results: We identified de novo SCN8A mutations in 7 patients: 6 of 60 unclassified EOEEs (10.0%), and one of 6 MMPSI cases (16.7%). The mutations were scattered through the entire gene: four mutations were located in linker regions, two in the fourth transmembrane segments, and one in the C-terminal domain. The type of the initial seizures was variable including generalized tonic-clonic, atypical absence, partial, apneic attack, febrile convulsion, and loss of tone and consciousness. Onset of seizures was during the neonatal period in two patients, and between 3 and 7 months of age in five patients. Brain magnetic resonance imaging (MRI) showed cerebellar and cerebral atrophy in one and six patients, respectively. All patients with SCN8A missense mutations showed initially uncontrollable seizures by any drugs, but eventually one was seizure-free and three were controlled at the last examination. All patients showed developmental delay or regression in infancy, resulting in severe intellectual disability. Significance: Our data reveal that SCN8A mutations can cause variable phenotypes, most of which can be diagnosed as unclassified EOEEs, and rarely as MMPSI. Together with previous reports, our study further indicates that genetic testing of SCN8A should be considered in children with unclassified severe epilepsy.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available