KCNA2 Epilepsy: Difference between revisions
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[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> | [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> | ||
{{#ev:youtube|_yV9ovVISes|300}}<ref>Epilepsy Foundation. Specific Gene Mutation Screening in Infants: Children’s Hosp. PA, Epilepsy Neurogenetics Initiative. Available from: https://www.youtube.com/watch?v=_yV9ovVISes [last accessed 5/5/2013]</ref> | |||
== Management / Interventions == | == Management / Interventions == | ||
Revision as of 12:12, 5 July 2023
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Introduction[edit | edit source]
KCNA2 epilepsy is an epileptic condition caused by a malfunction in the potassium channels located within the Central nervous System (CNS).[1]
Clinically Relevant Anatomy[edit | edit source]
KCNA2 is a gene located on chromosome 1p13.3. It encodes the voltage-gated potassium (K+) channels, many of which are located in the CNS. 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]
An electroencephalogram (EEG) is performed to define the epileptogenic zone.[8]The Epileptogenic zone is the region of the brain that generates the seizure.
An MRI can also be performed to analyze the structures of the brain, looking for any malformations or types of lesions commonly caused by epilepsy.[1]
Genetic testing is ultimately needed to detect mutations in the KCNA2 gene.
Whole Exome Sequencing (WES) is commonly performed in the literature 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]
Medical treatment[edit | edit source]
Allied treatment[edit | edit source]
As each individual presents differently, different intervention approaches are needed.
A common theme, however, in all research and information websites is the need for a team approach to the management and care of those with KCNA2. One such approach can be the multidisciplinary approach.
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 1.2 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.
- ↑ Life with Episodic Ataxia. Dominant KCNA2 gene mutaion causing episodic ataxia with tremor and erratic myoclonic jerks evident. Available from: https://www.youtube.com/watch?v=i572sSLEcN8 [last accessed 5/5/2013]
- ↑ Noachtar S, Rémi J. The role of EEG in epilepsy: a critical review. Epilepsy & Behavior. 2009 May 1;15(1):22-33.
- ↑ Epilepsy Foundation. Specific Gene Mutation Screening in Infants: Children’s Hosp. PA, Epilepsy Neurogenetics Initiative. Available from: https://www.youtube.com/watch?v=_yV9ovVISes [last accessed 5/5/2013]
