Abstracts

Rationale: As genetic epilepsy panels become more common, rare causes of epileptic encephalopathy are being discovered in patients with refractory epilepsy and/or developmental delay. One of these genes, SCN8A, has only been identified recently. Cases in the literature have shown a variety of clinical phenotypes, including seizures, intellectual disability, and motor manifestations. They often have intractable or difficult to control epilepsy that can cause developmental regression after seizure onset. Most patients to date have presented with de novo mutations. Much is unknown about the clinical phenotype and treatment of these patients. We present a series of six patients with SCN8A mutations, with 4 of 6 children uniquely inheriting their mutations from one or more healthy parents. Methods: We performed a retrospective chart review on 6 patients with identified SCN8A mutations by the GeneDx genetic epilepsy panel. All patients had parental testing; however, one child's mother only was tested. We reviewed their MRIs and EEGs. Results: We divided our patients into 3 groups. Group 1 ?" patients 1, 6 (seizure onset < 12 months old, with global developmental delay), myoclonic jerks, complex partial seizures, and hypotonia. Both had de novo mutations with negative parental testing. Their SCN8A mutations have not been reported. Group 2 ?" patients 4, 5 (brothers with consanguineous parents, who both carry the same mutation). They are relatively higher functioning, have some words, self-feed, ambulate independently, have autism, insomnia and anxiety. Both have generalized absence seizures, well controlled on monotherapy. Their mutations have not been reported. The other two patients do not fit in any specific phenotypic pattern. Patient 2: seizure onset at age 23 weeks (GTC). His development is normal at age 2 years old. MRI brain and initial EEG were normal; follow up EEG showed focal spikes with secondary generalization. His previously unreported mutation was inherited from his healthy father. Patient 3 had developmental delay at seizure onset at age 2 years old, with focal onset staring; initial EEG with focal spikes and slowing. Follow up EEG showed an epileptic encephalopathy, with multifocal and generalized spikes and generalized slowing. She is hypotonic and has choreoathetosis. Her mutation is inherited from her healthy father and has been reported as a mosaic. Conclusions: Our patients had a broad phenotype, from well-controlled to refractory epilepsy and various degrees of developmental impairment (full care to normal). In 4/6 patients, mutations were inherited from parents. Both focal and generalized epilepsy are seen, even in the same child, and can be easy to control or intractable. Three also had significant hypotonia, and one had a movement disorder. We hypothesize that there may be other factors beyond the mutation itself that causes the symptoms of their epilepsy and/or delays as compared to their parents. This warrants further study into the factors that modify the clinical phenotype differences between generations. Funding: None.