[P1-100] Autistic behaviors in a patient with de novo SCN8A mutation and rescued by lamotrigine
Autism spectrum disorders (ASD) is a pervasive neurodevelopmental disorder that is usually comorbid with epilepsy. SCN8A related disorders comprise a wide phenotypic spectrum, including infantile epileptic encephalopathy, intellectual disability, ataxia and autism spectrum disorder. In this case report, we describe a boy with a de novo mutation of Scn8a gene c.5492G>A (p.R1831Q) who developed epilepsy at 4 months of age and controlled well on oxcarbazepine for one year with normal development. At the time of admission, his seizure deteriorated to more than ten times per day with no recovery of consciousness during inter-ictal phases. He also developed choreaothetosis and hypotonia. Numerous drugs including clonazepam, valproate, topiramate, midazolam showed little effect on seizure control. During recovery, he manifested obvious developmental regression, particularly of the communication skills and repetitive behaviors. However, seizure stopped with the adding dose of lamotrigine, and with significant improvement of the language skills and behaviors. In previous studies, mice heterozygous for mutations in the Scn8a gene showed motor impairments and neuropsychological abnormalities, which are consistent findings in other animal models with autistic features. Consistent with findings in Tsc1 knockout purkinje cells (PCs) and PTEN knockout PCs, Scn8a knockout PCs have a lower frequency of spontaneous firing, are less excitable. We proposed Scn8a mutation has a plausible underlying pathophysiological mechanism related to autism. With this report, we provide further insight for the role of SCN8A in neurocognitive function, its implication in ASD. Suggesting SCN8A should be considered as a causative gene not only in cases of epileptic encephalopathy but also in children with autism.