Gabapentin treatment in a patient with KCNQ2 developmental epileptic encephalopathy
Maria Virginia Soldovieri, Elena Freri, Paolo Ambrosino, Ilaria Rivolta, Ilaria Mosca, Anna Binda, Carmen Murano, Francesca Ragona, Laura Canafoglia, Chiara Vannicola, Roberta Solazzi, Tiziana Granata, Barbara Castellotti, Giuliana Messina, Cinzia Gellera, Audrey Labalme, Gaëtan Lesca, Jacopo C. DiFrancesco, Maurizio Taglialatela
Abstract
) channel subunits are associated with developmental epileptic encephalopathy (DEE). We herein describe the clinical and electroencephalographic (EEG) features of a child with early-onset DEE caused by the novel KCNQ2 p.G310S variant. In vitro experiments demonstrated that the mutation induces loss-of-function effects on the currents produced by channels incorporating mutant subunits; these effects were counteracted by the selective Kv7 opener retigabine and by gabapentin, a recently described Kv7 activator. Given these data, the patient started treatment with gabapentin, showing a rapid and sustained clinical and EEG improvement over the following months. Overall, these results suggest that gabapentin can be regarded as a precision therapy for DEEs due to KCNQ2 loss-of-function mutations.