KCNA2 Epilepsy: Difference between revisions
No edit summary |
No edit summary |
||
| Line 8: | Line 8: | ||
== Introduction == | == Introduction == | ||
KCNA2 | KCNA2 [[epilepsy]] is an epileptic condition caused by a malfunction in the potassium channels located within the CNS.<ref name=":0">KCNA2 Epilepsy Organisation. What is KCNA2 Epilepsy. Available from: https://www.kcna2epilepsy.org/kcna2-epilepsy/what-is-kcna2-epilepsy/ (accessed 26 June 2023).</ref> | ||
== Clinically Relevant Anatomy == | |||
'''KCNA2''' is a gene located on chromosome 1p13.3. It encodes a voltage-gated potassium (K+) channel, many of which are located in the central nervous system. Mutations occurring in K+ channel-coding genes cause different neurological diseases. <ref name=":1">Wang H, Zhu Y, Cao D, Chen H, Ding X, Zeng Q, Zou H, Liao J. [https://aepi.biomedcentral.com/articles/10.1186/s42494-021-00069-7 Successful medical treatment of west syndrome with a KCNA2 variant: a case report]. Acta Epileptologica. 2022 Mar 2;4(1):6.</ref> | |||
== Mechanism of Injury / Pathological Process == | |||
KCNA2 epilepsy | '''KCNA2 epilepsy''' is caused by a variation in the '''KCNA2 gene''' leading to a malfunction in the K+ channel.<ref>McGinn RJ, Von Stein EL, Stromberg JE, Li Y. Precision medicine in epilepsy. [https://www.sciencedirect.com/science/article/abs/pii/S1877117322000473 Progress in Molecular Biology and Translational Science]. 2022 Jan 1;190(1):147-88.</ref><ref>Syrbe S, Hedrich U, Riesch E, Djémié T, Müller S, Møller RS, Maher B, Hernandez-Hernandez L, Synofzik M, Caglayan HS, Arslan M. [https://www.researchgate.net/publication/273383158_De_novo_loss-_or_gain-of-function_mutations_in_KCNA2_cause_epileptic_encephalopathy De novo loss-or gain-of-function mutations in KCNA2 cause epileptic encephalopathy]. Nature genetics. 2015 Apr;47(4):393-9.</ref><ref name=":1" /> | ||
= | Malfunction of the KCNA2 channels can be seen as 3 different [https://www.genome.gov/genetics-glossary/Phenotype phenotypes]:<ref name=":0" /> | ||
# '''A gain of function (GOF)''' - where the channel does not close properly. This leads to an increased amount of K+ in the brain. | |||
# '''A loss of function''' '''(LOF)''' - where the channel does not open properly. This leads to a low amount of K+ in the brain. | |||
# '''A mix of functions''' - Where the K+ channel does both. | |||
In all three malfunctions, epilepsy may be observed. | |||
== Clinical Presentation == | == Clinical Presentation == | ||
KCNA2 epilepsy is often linked with encephalopathy in the research literature.<ref>Masnada S, Hedrich UB, Gardella E, Schubert J, Kaiwar C, Klee EW, Lanpher BC, Gavrilova RH, Synofzik M, Bast T, Gorman K. [https://www.researchgate.net/publication/320372444_Clinical_spectrum_and_genotype-phenotype_associations_of_KCNA2-related_encephalopathies Clinical spectrum and genotype–phenotype associations of KCNA2-related encephalopathies.] Brain. 2017 Sep 1;140(9):2337-54.</ref> Encephalopathy itself can be defined as a "... dysfunction of the level or contents of consciousness due to brain dysfunction and can result from global brain insults or focal lesions." <ref>Erkkinen MG, Berkowitz AL. [https://www.amjmed.com/article/S0002-9343(19)30571-6/fulltext A clinical approach to diagnosing encephalopathy]. The American Journal of Medicine. 2019 Oct 1;132(10):1142-7.</ref> | |||
= | LOF is the most common phenotype presented in the literature. It has been reported that epilepsy in this group tends to have an early onset - within infancy or early childhood. Intellectual disability (mild-to-moderate) and motor regression often appear after the onset of seizures. Ataxia has been associated with LOF.<ref name=":1" /> | ||
GOF has also been linked to ataxia and intellectual disability, with the severity of these presentations as well as seizures being greater. In addition, hypotonia and myoclonus have also been reported for this phenotype.<ref name=":1" /> | |||
The mixed phenotype can present with particularly severe seizures and conditions described in the LOF and GOF phenotypes. | |||
== Diagnostic Procedures == | |||
Whole Exome Sequencing (WES) is performed in order to identify KCNA2 mutations. This is a sequencing done of the exome - the coding portion of the genome. | |||
[https://www.nature.com/articles/jhg2013114 The Promise of Whole-Exome Sequencing in Medical Genetics] is an article that discusses this procedure and its development in more detail.<br> | |||
== Management / Interventions<br> == | == Management / Interventions<br> == | ||
<br> | |||
== Resources <br> == | == Resources <br> == | ||
* [https://www.kcna2epilepsy.org/ KCNA2 Global Support Community] | |||
* [https://www.rareepilepsynetwork.org/post/get-to-know-kcna2 Get to Know KCNA2] page on the Rare Epilepsy Network website | |||
== References == | == References == | ||
<references /> | <references /> | ||
Revision as of 14:45, 30 June 2023
This article or area is currently under construction and may only be partially complete. Please come back soon to see the finished work! (30/06/2023)
Introduction[edit | edit source]
KCNA2 epilepsy is an epileptic condition caused by a malfunction in the potassium channels located within the CNS.[1]
Clinically Relevant Anatomy[edit | edit source]
KCNA2 is a gene located on chromosome 1p13.3. It encodes a voltage-gated potassium (K+) channel, many of which are located in the central nervous system. Mutations occurring in K+ channel-coding genes cause different neurological diseases. [2]
Mechanism of Injury / Pathological Process[edit | edit source]
KCNA2 epilepsy is caused by a variation in the KCNA2 gene leading to a malfunction in the K+ channel.[3][4][2]
Malfunction of the KCNA2 channels can be seen as 3 different phenotypes:[1]
- A gain of function (GOF) - where the channel does not close properly. This leads to an increased amount of K+ in the brain.
- A loss of function (LOF) - where the channel does not open properly. This leads to a low amount of K+ in the brain.
- A mix of functions - Where the K+ channel does both.
In all three malfunctions, epilepsy may be observed.
Clinical Presentation[edit | edit source]
KCNA2 epilepsy is often linked with encephalopathy in the research literature.[5] Encephalopathy itself can be defined as a "... dysfunction of the level or contents of consciousness due to brain dysfunction and can result from global brain insults or focal lesions." [6]
LOF is the most common phenotype presented in the literature. It has been reported that epilepsy in this group tends to have an early onset - within infancy or early childhood. Intellectual disability (mild-to-moderate) and motor regression often appear after the onset of seizures. Ataxia has been associated with LOF.[2]
GOF has also been linked to ataxia and intellectual disability, with the severity of these presentations as well as seizures being greater. In addition, hypotonia and myoclonus have also been reported for this phenotype.[2]
The mixed phenotype can present with particularly severe seizures and conditions described in the LOF and GOF phenotypes.
Diagnostic Procedures[edit | edit source]
Whole Exome Sequencing (WES) is performed in order to identify KCNA2 mutations. This is a sequencing done of the exome - the coding portion of the genome.
The Promise of Whole-Exome Sequencing in Medical Genetics is an article that discusses this procedure and its development in more detail.
Management / Interventions
[edit | edit source]
Resources
[edit | edit source]
- KCNA2 Global Support Community
- Get to Know KCNA2 page on the Rare Epilepsy Network website
References[edit | edit source]
- ↑ 1.0 1.1 KCNA2 Epilepsy Organisation. What is KCNA2 Epilepsy. Available from: https://www.kcna2epilepsy.org/kcna2-epilepsy/what-is-kcna2-epilepsy/ (accessed 26 June 2023).
- ↑ 2.0 2.1 2.2 2.3 Wang H, Zhu Y, Cao D, Chen H, Ding X, Zeng Q, Zou H, Liao J. Successful medical treatment of west syndrome with a KCNA2 variant: a case report. Acta Epileptologica. 2022 Mar 2;4(1):6.
- ↑ McGinn RJ, Von Stein EL, Stromberg JE, Li Y. Precision medicine in epilepsy. Progress in Molecular Biology and Translational Science. 2022 Jan 1;190(1):147-88.
- ↑ Syrbe S, Hedrich U, Riesch E, Djémié T, Müller S, Møller RS, Maher B, Hernandez-Hernandez L, Synofzik M, Caglayan HS, Arslan M. De novo loss-or gain-of-function mutations in KCNA2 cause epileptic encephalopathy. Nature genetics. 2015 Apr;47(4):393-9.
- ↑ Masnada S, Hedrich UB, Gardella E, Schubert J, Kaiwar C, Klee EW, Lanpher BC, Gavrilova RH, Synofzik M, Bast T, Gorman K. Clinical spectrum and genotype–phenotype associations of KCNA2-related encephalopathies. Brain. 2017 Sep 1;140(9):2337-54.
- ↑ Erkkinen MG, Berkowitz AL. A clinical approach to diagnosing encephalopathy. The American Journal of Medicine. 2019 Oct 1;132(10):1142-7.
