Genetic and phenotypic characteristics of SCN1A-related epilepsy in Chinese children

SCN1A gene mutations are associated with epilepsy and neurodevelopmental disorders. This study aimed to explore the genotype and phenotype spectrum of SCN1A gene related epilepsy. Epileptic patients who were treated in the Children's Hospital of Chongqing Medical University from January 2015 to July 2018 and identified as having SCN1A mutations by targeted next-generation sequencing were included. Clinical manifestations of all patients were analyzed retrospectively. A total of 24 patients with SCN1A mutations were identified. The age of epilepsy onset ranged from 2 months to 2 years and 9 months. Multiple seizure types were observed. A total of 13 (54.2%) patients had three or more types of seizures. Overall, 16 (66.7%) patients had status epilepticus, 11 (45.8%) patients had fever sensitivity, and nine (37.5%) patients had seizures after vaccination. Moreover, 15 (62.5%) patients showed varying degrees of cognitive and motor development retardation. In addition, two patients had mutations inherited from one of their parents and 22 (91.7%) patients had de novo mutations. The following SCN1A mutation types were identified: missense (16 patients, 66.7%), nonsense (four patients, 16.7%), splice site (one patient), frameshift (one patient), and large deletions (two patients). Overall, 23 of the patients received antiepileptic therapy, of which eight (33.3%) patients had no decrease in seizures and 11 (45.8%) patients had more than 50% decrease in seizure frequency. Three patients had poor response to antiepileptic drug therapy before attempting ketogenic diet, after which seizure frequency decreased by 50%. A total of 10 (41.7%) patients had used sodium channel blockers before accurate diagnosis, all of whom showed ineffective or even aggravated seizure response. SCN1A mutations are associated with a spectrum of seizure-related disorders, ranging from a relatively mild form of febrile seizures to a more severe epileptic encephalopathy known as Dravet syndrome. Early diagnosis of SCN1A mutation-associated epilepsy can aid in appropriate choice of antiepileptic drugs for treatment and reducing adverse sequelae.