De novo variants in KCNQ2 encoding for Kv7.2 voltage-dependent neuronal potassium (K+) channel subunits are associated with developmental epileptic encephalopathy (DEE). We herein describe a 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.

Soldovieri, M., Freri, E., Ambrosino, P., Rivolta, I., Mosca, I., Binda, A., et al. (2020). Gabapentin treatment in a patient with KCNQ2 developmental epileptic encephalopathy. PHARMACOLOGICAL RESEARCH, 160 [10.1016/j.phrs.2020.105200].

Gabapentin treatment in a patient with KCNQ2 developmental epileptic encephalopathy

Rivolta, Ilaria;Binda, Anna;Murano, Carmen;DiFrancesco, Jacopo C.
;
2020

Abstract

De novo variants in KCNQ2 encoding for Kv7.2 voltage-dependent neuronal potassium (K+) channel subunits are associated with developmental epileptic encephalopathy (DEE). We herein describe a 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.
Articolo in rivista - Articolo scientifico
epilepsy; developmental and epileptic encephalopathy; KCNQ2; Gabapentin; precision medicine; loss-of-function
English
15-set-2020
2020
160
105200
none
Soldovieri, M., Freri, E., Ambrosino, P., Rivolta, I., Mosca, I., Binda, A., et al. (2020). Gabapentin treatment in a patient with KCNQ2 developmental epileptic encephalopathy. PHARMACOLOGICAL RESEARCH, 160 [10.1016/j.phrs.2020.105200].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/284880
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