Abstract
Mutations in the Potassium channel subfamily T member 1 (KCNT1) gene have been reported in a range of epileptic encephalopathies. Here we report the case of a 12-year-old male suffering from multiple types of epileptic seizures and cognitive decline from the age of 10. The patient had four types of epileptic seizures, including tonic seizures, atypical absence seizures, myoclonic seizures, and generalized tonic-clonic seizures. The electroencephalogram showed generalized slow spike-and-slow-waves, mutiple-spike-and-slow-waves, as well as short-term fast rhythms bursts. Thus, he was diagnosed with Lennox-Gastaut syndrome. The patient had failed to control seizures after using five first-line antiepileptic drugs. Whole exome sequencing revealed a missense KCNT1 mutation (c.625 C>T). Previous studies revealed that quinidine could block the KCNT1 channel. Therefore, we assumed that quinidine might be effective for him. Add-on treatment with quinidine was started when the patient was 12 years old. After an 8-month treatment, the frequency of seizures and epileptiform discharges were significantly reduced. In conclusion, quinidine therapy may offer a new choice for the treatment of Lennox-Gastaut syndrome with KCNT1 mutations.
Highlights
Potassium channel subfamily T member 1 (KCNT1), known as Slack, is a member of the Slo-type sub family of potassium channel genes [1,2,3]
KCNT1 mutations enhance the channel-mediated potassium conductance and increase the K+ currents in neurons and interneurons, which result in the imbalance between neuronal excitation and inhibition [10, 11]
Our study suggested that quinidine therapy might offer a new method for the treatment of KCNT1-related epilepsy syndromes
Summary
Potassium channel subfamily T member 1 (KCNT1), known as Slack, is a member of the Slo-type sub family of potassium channel genes [1,2,3]. There have been several reports about the quinidine treatment of KCNT1-related epileptic encephalopathies, such as EIMFS, ADNFLE, and West syndrome [10, 13,14,15,16]. We report a patient suffering from Lennox-Gastaut syndrome with a missense mutation in KCNT1 (c.625C>T) treated with quinidine. The patient was diagnosed with Lennox-Gastaut syndrome after considering his multiple types of epileptic seizures, mental retardation, and typical electroencephalographic features. He was refractory to a multiple anti-epileptic drugs treatment, including sodium valproate (8 mg/kg/day), levetiracetam (50 mg/kg/day), clonazepam (0.0375 mg/kg/day), topiramate (3.75 mg/kg/day), and lamotrigine (2.5 mg/kg/day). After 1 month of treatment, the dose of quinidine was titrated to 10 mg/kg/day and he had 13 tonic seizures during this month.
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