Seizures, Epilepsy, and Genetics
Content Researched and Written by Ilham Abbasi
Reviewed for Scientific Accuracy by Andrew J. McCarty, MS, CGC and Rachel Baer, MSc
What is Epilepsy?
Epilepsy is one the leading causes of brain disorders, with an estimated 3.4 million people with active epilepsy in the United States alone. The major sign of epilepsy is recurrent seizures (1,2).
Seizures vs Epilepsy
Epileptic seizures are caused by abnormal bursts of electricity in the brain and can be of many different types.
Seizures are commonly classified into two groups: Generalized Seizures and Partial / Focal Seizures
Some common terms used to describe a seizure include(2):
Tonic: When body muscles stiffen
Atonic: When body muscles relax
Clonic: Repetitive periods of body shaking or jerking
Status Epilepticus: A seizure that lasts longer than 5 minutes without returning to a normal level of consciousness between episodes
Generalized seizures: These are common in genetic epilepsies and occur across the entire surface of the brain.
Types of generalized seizures include:
Absence seizures: can cause a person to blank out or stare into space
Tonic-clonic seizures: can cause a person to fall, lose consciousness, and experience muscle jerks
Partial or Focal Seizures: These are common in seizures caused by brain damage or brain disorders and occur in one specific area of the brain.
Types of partial seizures include:
Simple partial seizures: can cause a person to twitch or experience changes in their sensations such as taste or smell
Complex partial seizures: can cause a person to become confused, dazed, and unable to move
Secondary generalized seizures: begin as a partial seizure and spread to the entire brain, causing a person to experience a partial seizure followed by a generalized seizure
The Genetics of Epilepsy
A genetic epilepsy is one in which a person has a change in DNA or multiple atypical changes in DNA that increase the likelihood of a seizure occurring (4). Over 50% of epilepsies have an underlying genetic component, although it is important to know that many epilepsies can have both a genetic and environmental component (3). Genetic epilepsies can either be inherited or de novo. Inherited epilepsies involve an epileptic DNA change that is passed down from a parent. De novo epilepsies involve a new change in DNA that increases the chance of a seizure occurring. This DNA change is not inherited from a parent but may now be heritable in future generations. Different underlying genetic factors can lead to different types of seizures (4).
CDKL5 disorder: CDKL5 disorder is a rare genetic epilepsy disorder caused by changes in the CDKL5 gene. The abnormal DNA change is found on the X chromosome and affects the CDKL5 protein which is important for healthy brain development. Symptoms begin early in life, usually begin a few months following birth, with females being more frequently affected than males. There is currently no cure for CDKL5 disorder but research is trying to better understand the disorder so that targeted treatments can be identified in the future (4).
PCDH19 Epilepsy: PCDH19 Epilepsy is a rare form of epilepsy that causes seizures, behavioral problems, and cognitive delays. The PCDH19 gene causes a protein called protocadherin to be made which plays a role in brain communication, however, in this form of epilepsy, the protein isn’t made correctly or isn’t made at all. 15000 to 30000 people in the United States have this form of epilepsy, and it is more common in girls – about 1 in 10 girls who have this condition will develop seizures by the age of 5 (4).
Pyridoxine-dependent epilepsy (PDE): PDE is a rare genetic epilepsy that causes stubborn seizures in newborns, infants, and children. PDE is caused by changes in the ALDH7A1 gene, which is responsible for the formation of Antiquitin, a protein that breaks down the amino acid lysine. Changes in the ALDH7A1 gene lead to abnormal lysine breakdown which disrupts healthy brain development. Individuals with PDE are often recommended a lysine restricted diet due to their inability to correctly break down lysine. Pyridoxine supplements are another common treatment, as individuals with PDE also require higher levels of the vitamin (5, 6).
Treatment:
Aside from precision medicine, there are many general treatments that can be used to prevent or completely stop seizures from occurring. For example:
Anti-epileptic drugs (AEDs): AEDs are the most common epilepsy treatment. AEDs prevent seizures by altering the brain's chemical balance. Depending on the type of seizures someone is experiencing, their doctor may recommend different AEDs (7, 8).
Brain Surgery: Brain surgery may be recommended when AEDs do not work and there is a small area of the brain that is causing the seizures which can be removed. Several tests must be done before determining if this is a suitable option (7, 8).
Specialized Diets: Specialized diets, such as the ketogenic diet, uses high fats and low carbohydrates to alter the brain's chemical levels. This treatment is often recommended for children when AEDs are not effective (7, 8).
Electrical Devices: Vagus nerve stimulation (VNS) can be used to place an electrical device similar to a pacemaker under the chest. This device helps prevent seizures by altering the brain’s electrical signals. Deep brain stimulation (DBS) is a similar but newer procedure to VNS in which a device is also placed under the chest to change the brain’s electrical signals. The major difference between VNS and DBS is how the electrical wires connect to the brain. Because DBS is newer, its effectiveness for epilepsy isn’t as clear (7, 8).
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