KCNA1 gain‐of‐function epileptic encephalopathy treated with 4‐aminopyridine

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‐fu...

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Autores principales: Müller, Peter, Takacs, Danielle S., Hedrich, Ulrike B. S., Coorg, Rohini, Masters, Laura, Glinton, Kevin E., Dai, Hongzheng, Cokley, Jon A., Riviello, James J., Lerche, Holger, Cooper, Edward C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Brief Communications
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10109319/
https://www.ncbi.nlm.nih.gov/pubmed/36793218
http://dx.doi.org/10.1002/acn3.51742
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author Müller, Peter
Takacs, Danielle S.
Hedrich, Ulrike B. S.
Coorg, Rohini
Masters, Laura
Glinton, Kevin E.
Dai, Hongzheng
Cokley, Jon A.
Riviello, James J.
Lerche, Holger
Cooper, Edward C.
author_facet Müller, Peter
Takacs, Danielle S.
Hedrich, Ulrike B. S.
Coorg, Rohini
Masters, Laura
Glinton, Kevin E.
Dai, Hongzheng
Cokley, Jon A.
Riviello, James J.
Lerche, Holger
Cooper, Edward C.
author_sort Müller, Peter
collection PubMed
description 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.
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spelling pubmed-101093192023-04-18 KCNA1 gain‐of‐function epileptic encephalopathy treated with 4‐aminopyridine Müller, Peter Takacs, Danielle S. Hedrich, Ulrike B. S. Coorg, Rohini Masters, Laura Glinton, Kevin E. Dai, Hongzheng Cokley, Jon A. Riviello, James J. Lerche, Holger Cooper, Edward C. Ann Clin Transl Neurol Brief Communications 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. John Wiley and Sons Inc. 2023-02-15 /pmc/articles/PMC10109319/ /pubmed/36793218 http://dx.doi.org/10.1002/acn3.51742 Text en © 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Brief Communications
Müller, Peter
Takacs, Danielle S.
Hedrich, Ulrike B. S.
Coorg, Rohini
Masters, Laura
Glinton, Kevin E.
Dai, Hongzheng
Cokley, Jon A.
Riviello, James J.
Lerche, Holger
Cooper, Edward C.
KCNA1 gain‐of‐function epileptic encephalopathy treated with 4‐aminopyridine
title KCNA1 gain‐of‐function epileptic encephalopathy treated with 4‐aminopyridine
title_full KCNA1 gain‐of‐function epileptic encephalopathy treated with 4‐aminopyridine
title_fullStr KCNA1 gain‐of‐function epileptic encephalopathy treated with 4‐aminopyridine
title_full_unstemmed KCNA1 gain‐of‐function epileptic encephalopathy treated with 4‐aminopyridine
title_short KCNA1 gain‐of‐function epileptic encephalopathy treated with 4‐aminopyridine
title_sort kcna1 gain‐of‐function epileptic encephalopathy treated with 4‐aminopyridine
topic Brief Communications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10109319/
https://www.ncbi.nlm.nih.gov/pubmed/36793218
http://dx.doi.org/10.1002/acn3.51742
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