Medicine and Health Sciences Commons^™

The Gain Of Function Scn1a Disorder Spectrum: Novel Epilepsy Phenotypes And Therapeutic Implications, Andreas Brunklaus, Tobias Brünger, Tony Feng, Carmen Fons, Anni Lehikoinen, Eleni Panagiotakaki, Mihaela Adela Vintan, Joseph Symonds, James Andrew, Alexis Arzimanoglou, Sarah Delima, Julie Gallois, Donncha Hanrahan, Gaetan Lesca, Stewart Macleod, Dragan Marjanovic, Amy Mctague, Noemi Nuñez-Enamorado, Eduardo Perez-Palma, M. Scott Perry, Karen Pysden, Sophie J. Russ-Hall, Ingrid E. Scheffer, Krystal Sully, Steffen Syrbe, Ulvi Vaher, Murugan Velayutham

School of Medicine Faculty Publications

Brain voltage-gated sodium channel NaV1.1 (SCN1A) loss-of-function variants cause the severe epilepsy Dravet syndrome, as well as milder phenotypes associated with genetic epilepsy with febrile seizures plus. Gain of function SCN1A variants are associated with familial hemiplegic migraine type 3. Novel SCN1A-related phenotypes have been described including early infantile developmental and epileptic encephalopathy with movement disorder, and more recently neonatal presentations with arthrogryposis. Here we describe the clinical, genetic and functional evaluation of affected individuals. Thirty-five patients were ascertained via an international collaborative network using a structured clinical questionnaire and from the literature. We performed whole-cell voltage-clamp electrophysiological recordings comparing …