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P.036 Targeted molecular therapy with quinidine for seizures in a neonate with KCNT1 mutation leads to poor response

  • JM Smith (a1), M Patel (a1), Q Xu (a1), S Uliel-Sibony (a1), M Demos (a1), M Connolly (a1), A Datta (a1) and L Looned (a1)...

Abstract

Background: The KCNT1 gene encodes subunits of the Na+-activated K+ channel, widely expressed in the CNS. Mutations of this gene have been implicated in Malignant Migrating Partial Seizures of Infancy (MMPSI). This early-onset epileptic encephalopathy represents a challenge due to pharmacoresistance. The channel-specific mutation represents the potential for targeted pharmacotherapy. Quinidine is a partial antagonist of the KCNT1 encoded channel; patients with MMPSI have been reported to have responded to doses ranging 34.4/kg/d - 60mg/kg/d. We present a case of MMPSI with a KCNTI mutation (c.G1283A:p.R428Q) trialled on quinidine. Methods: Following ineffective trials of 6 anti-seizure medications, this patient was trialled on oral quinidine. This patient was titrated up to a dose of 52mg/kg/d. Twenty-four hour EEG monitoring prior to quinidine therapy, and at target dose were compared. Results: Prior to initiation of quinidine, this patient experienced 22 electrographic seizures over 24 hours. At target dose, this patient experienced greater than 70 seizures over 24 hours. Conclusions: Quinidine has previously been reported to be effective in patients with MMPSI with the same and different mutations. We report the second case of a patient with MMPSI and KCNT1 mutation R428Q with poor clinical response to quinidine.

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