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KCNA1 gain-of-function epileptic encephalopathy treated with 4-aminopyridine.

ABSTRACT: Precision medicine for Mendelian epilepsy is rapidly developing. We describe an early infant with severely pharmacoresistant multifocal epilepsy. Exome sequencing revealed the de novo variant p.(Leu296Phe) in the gene KCNA1, encoding the voltage-gated K⁺ channel subunit K_V 1.1. So far, loss-of-function variants in KCNA1 have been associated with episodic ataxia type 1 or epilepsy. Functional studies of the mutated subunit in oocytes revealed a gain-of-function caused by a hyperpolarizing shift of voltage dependence. Leu296Phe channels are sensitive to block by 4-aminopyridine. Clinical use of 4-aminopyridine was associated with reduced seizure burden, enabled simplification of co-medication and prevented rehospitalization.

SUBMITTER: Muller P

PROVIDER: S-EPMC10109319 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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KCNA1 gain-of-function epileptic encephalopathy treated with 4-aminopyridine.

Müller Peter P Takacs Danielle S DS Hedrich Ulrike B S UBS Coorg Rohini R Masters Laura L Glinton Kevin E KE Dai Hongzheng H Cokley Jon A JA Riviello James J JJ Lerche Holger H Cooper Edward C EC

Annals of clinical and translational neurology 20230215 4

Precision medicine for Mendelian epilepsy is rapidly developing. We describe an early infant with severely pharmacoresistant multifocal epilepsy. Exome sequencing revealed the de novo variant p.(Leu296Phe) in the gene KCNA1, encoding the voltage-gated K<sup>+</sup> channel subunit K<sub>V</sub> 1.1. So far, loss-of-function variants in KCNA1 have been associated with episodic ataxia type 1 or epilepsy. Functional studies of the mutated subunit in oocytes revealed a gain-of-function caused by a h ...[more]

PMID: 36793218

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Complete loss of KCNA1 activity causes neonatal epileptic encephalopathy and dyskinesia.

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Project description: Not available

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Gain-of-function FHF1 mutation causes early-onset epileptic encephalopathy with cerebellar atrophy.

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