Abstract Title

Concomitant Mutations of Sodium Channels SCN8A and SCN2A Cause Dravet Syndrome Phenotype

Presenter Name

Chethan K. Rao, MS

Abstract

Purpose: To report a unique case of Dravet Syndrome (DS) and investigate the relationship between inherited SCN2A and de novo SCN8A mutations in our patient; to determine whether a de novo SCN8A mutation can cause DS; to review the genetic causes of DS phenotype and the need for thorough genetic evaluation for SCN1A-negative DS cases

Methods: In this observational, retrospective case study, we focused on patient records analysis including whole-exome sequencing, EEG, and MRI.

Results: This study found reason to believe that the de novo SCN8A mutation acted as a phenotypic modifier of the inherited SCN2A mutation, resulting in DS. The study also found a significant need for genetic evaluation beyond SCN1A mutations. In addition, Stiripentol was found to be an effective treatment for DS in this patient.

Conclusions: Based on our findings and those of relevant studies, our patient’s de novo SCN8A mutation likely acted as a phenotypic modifier of the inherited SCN2A mutation potentially through a “two-hit” mechanism. The vast array of genetic etiologies of DS warrants thorough genetic testing beyond the most common SCN1A mutation. Stiripentol, though currently an investigative drug, shows promise as an effective therapeutic agent in our patient and potentially other cases of non-SCN1A DS.

Presentation Type

Poster

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Concomitant Mutations of Sodium Channels SCN8A and SCN2A Cause Dravet Syndrome Phenotype

Purpose: To report a unique case of Dravet Syndrome (DS) and investigate the relationship between inherited SCN2A and de novo SCN8A mutations in our patient; to determine whether a de novo SCN8A mutation can cause DS; to review the genetic causes of DS phenotype and the need for thorough genetic evaluation for SCN1A-negative DS cases

Methods: In this observational, retrospective case study, we focused on patient records analysis including whole-exome sequencing, EEG, and MRI.

Results: This study found reason to believe that the de novo SCN8A mutation acted as a phenotypic modifier of the inherited SCN2A mutation, resulting in DS. The study also found a significant need for genetic evaluation beyond SCN1A mutations. In addition, Stiripentol was found to be an effective treatment for DS in this patient.

Conclusions: Based on our findings and those of relevant studies, our patient’s de novo SCN8A mutation likely acted as a phenotypic modifier of the inherited SCN2A mutation potentially through a “two-hit” mechanism. The vast array of genetic etiologies of DS warrants thorough genetic testing beyond the most common SCN1A mutation. Stiripentol, though currently an investigative drug, shows promise as an effective therapeutic agent in our patient and potentially other cases of non-SCN1A DS.