Epilepsy (ILAEC, 2014) – Is epilepsy genetic?

salt

Nebula Genomics DNA Report for Epilepsy

Is epilepsy genetic? We created a DNA report based on a study that attempted to answer this question. Below you can see a SAMPLE DNA report. To get your personalized DNA report, purchase our Whole Genome Sequencing!

Is epilepsy genetic? A sample epilepsy report from Nebula Genomics
A sample report of epilepsy genetic variants from Nebula Genomics

To learn more about how Nebula Genomics reports genetic variants in the table above, check out the Nebula Research Library Tutorial.

Additional Information

What is epilepsy? (Part 1 of Is epilepsy genetic?)

Epilepsy, sometimes referred to as cerebral seizure disorder or cerebral spasm disorder, refers to a brain disorder with at least one spontaneously occurring epileptic seizure. There is currently no existing identifiable cause (such as an acute inflammation of the brain, a stroke or brain injury/head injury) or trigger (such as withdrawal of alcohol in the case of existing alcohol dependency or massive sleep deprivation). 

Epilepsy is a chronic disorder that can be diagnosed when unprovoked seizures occur at a recognizably high risk of recurrence. The disorder is characterized by unpredictable seizures and can cause other health problems. It is also known as a spectrum condition with a wide range of seizure types and control varying from person-to-person. 

Biologically, an epileptic seizure is a consequence of sudden, synchronous electrical discharges of nerve cells (neuron groups) in the brain, which lead to involuntary stereotypical movement or mental health disorders. The exact activity in the brain can be unique. The location of the event, how it spreads, how much of the brain is affected, and how long it lasts all have profound effects. 

The anatomy of a nerve cell
During a seizure, brain cells release electrical discharge suddenly. Wikipedia. CC-Attribution 3.0 Unported.

For more information, the Epilepsy Foundation (copyright 2020) is a non-profit aimed to help people with epilepsy. Their website is full of helpful information and resources.

Is Epilepsy Genetic?

Some types of epilepsy tend to run in families. Not all epilepsies due to a genetic cause are inherited epilepsy. Other types may be due to genetic changes that were inherited or happened for the first time in an individual. In such instances, there may not have been any family history of epilepsy. 

If a person has a close family member with epilepsy, the risk of them developing the disorder by the age of 40 is less than 1 in 20 although there is an increased risk of epilepsy if the first-degree relative has a generalized epilepsy rather than focal epilepsy. 

The first few epilepsy-related genes were identified in the late 1990s. Advances in DNA sequencing now have identified hundreds of genes that play a role in epilepsy.

Some of these genes associated with epilepsy disorder include ALDH7A4, DEPDC5, EPM2A, GABARG2, GRIN2A, KCNQ2, LGI1, PCDH19, POLG, SCN1A, and STXBP1.

In addition, epilepsy can also occur in diseases that are based on a change in the genetic make-up. In these cases, the seizure is only a symptom of the disease. Examples are tuberous sclerosis or Angelman syndrome.

Epidemiology (Part 3 of Is epilepsy genetic?)

According to the CDC, in 2015, 1.2% of the US population (3.4 million people) had active epilepsy. This number includes 3 million adults and 470,000 children with epilepsy.  

An adult aged 18 or older has active epilepsy if they report they have a history of doctor-diagnosed epilepsy or seizure disorder and are currently taking medication to control it and/or had one or more seizures in the past year.

A child aged 17 years or younger has active epilepsy if their parent or guardian reports that a doctor or health care provider has ever told them that their child had epilepsy or seizure disorder and if their child currently has epilepsy or seizure disorder.

The prevalence of epilepsy in the United States
The highest prevalence of epilepsy worldwide is on the continent of Africa. Wikipedia. CC-Attribution-Share Alike 2.5 Generic.

Epilepsy affects both males and females of all races, ethnic backgrounds and ages.

Symptoms (Part 4 of Is epilepsy genetic?)

Recurrent seizures are a hallmark of epilepsy. Seizure symptoms can vary greatly between individuals although most patients living with epilepsy tend to have the same types of seizures. Usually, to be diagnosed as epilepsy, an individual has at least two unprovoked seizures. 

Mayo Clinic notes the most common symptoms of seizures:

  • Temporary confusion
  • A staring spell
  • Uncontrollable jerking movements of the arms and legs
  • Loss of consciousness or awareness
  • Psychic symptoms such as fear, anxiety or deja vu

Forms of epilepsy may appear as one of two types of seizures, focal or generalized.

Focal seizures

Focal seizures originate in one portion of the brain. They may occur without loss of consciousness, where the patient experiences altered emotions or changes the way things look, smell, feel, taste or sound. They may also experience involuntary jerking of a body part, such as an arm or leg, and spontaneous sensory symptoms such as tingling, dizziness and flashing lights. Focal seizures can also occur with impaired awareness where the individual either loses consciousness or behaves strangely with their environment, such as staring blankly.

Generalized seizures

Generalized seizures affect the entire brain. They are classified into six categories:

  1. Absence seizures often occur in children and are characterized by staring into space or subtle body movements such as eye blinking or lip smacking. 
  2. Tonic seizures cause stiffening of your muscles. 
  3. Atonic seizures cause a loss of muscle control, which may cause you to suddenly collapse or fall down.
  4. Clonic seizures are associated with repeated or rhythmic, jerking muscle movements. These seizures usually affect the neck, face and arms.
  5. Myoclonic seizures usually appear as sudden brief jerks or twitches of your arms and legs.
  6. Tonic-clonic seizures are the most dramatic type of epileptic seizure and can cause an abrupt loss of consciousness, body stiffening and shaking, and sometimes loss of bladder control or biting your tongue.

For some patients, the risk of sudden unexpected death in epilepsy (SUDEP) is a concern. Death occurs without any other underlying cause and normally occurs immediately after the occurrence of a seizure.

Causes of Epilepsy (Part 5 of Is epilepsy genetic?)

Although knowledge about the development of epilepsy has increased significantly in recent decades, much is still unknown. The occurrence of epileptic seizures is caused by the over-excitability of nerve cells, and abnormal brain electrical activity of larger nerve cell assemblies. It is therefore assumed that an imbalance of excitation and inhibition in these neural networks leads to epileptic seizures. About 3 out of 10 people have a change in the structure of their brains that causes the electrical storms of seizures. 

Increased excitation or decreased inhibition of brain cells can be caused both by changes in the membrane properties of the nerve stimulator cells, and in the transmission of excitation from nerve cell to nerve cell by neurotransmitters. For example, defects in the ion channels for sodium and calcium ions can participate in the generation and propagation of seizure discharges.

Epileptic seizures
Epilpetic seizures are biologically a result of overexcited nerve cells. Pixabay.

Often, the cause of seizures is associated with the age of the patient. The Epilepsy Foundation summarizes what triggers seizures in patients of various ages:

Newborns may have seizures due to prenatal factors such as brain malformations, lack of oxygen during birth, low levels of blood sugar, blood calcium, blood magnesium or other electrolyte problems, inborn errors of metabolism, intracranial hemorrhage, and maternal drug use. Infants and children are most susceptible to fever, brain tumor (rarely), or infections (scarring in the brain).

Children and young adult seizures are most commonly brought on by congenital conditions (Down’s syndrome; Angelman’s syndrome; tuberous sclerosis and neurofibromatosis), genetic factors, progressive brain disease (rare), or head trauma. Brain damage can occur at any age, but is most prevalent and serious in young adults. In seniors, stroke, Alzheimer’s disease (you can read more about the genetics of Alzheimer’s disease and dementia in our Research Library), or trauma is most likely the cause.

Diagnosis (Part 6 of Is epilepsy genetic?)

For diagnosis, the medical history of people who have had a seizure is taken. Doctors try to understand if the event was in fact a real seizure, if it was a seizure, if it was caused by epilepsy, and the type of seizures that are occuring. 

Patients are also asked about family history of epilepsy, other diseases of the nervous system, and to previous illnesses that may cause symptomatic epilepsy. These include disorders and increased risk to women with epilepsy during pregnancy, problems during childbirth leading to oxygen deficiency, accidents with craniocerebral trauma (brain conditions) or inflammatory diseases of the central nervous system.

This is followed by a physical examination, especially of the nervous system, with examination of strength, feeling (sensitivity), reflexes, cranial nerve function, balance and coordination.

Blood tests are also used to identify possible causes of symptomatic epileptic seizures (such as hypoglycaemia or mineral deficiency). They also test for signs of kidney or liver malfunction, and other common problems. A lumbar puncture (sometimes called a spinal tap) may be used to rule out infections, like meningitis and encephalitis and a toxicology screen may be used to look for toxins.

Typically, an electroencephalogram is performed. Imaging is usually part of routine diagnostics, while more specialized procedures are reserved for special questions.

Electroencephalogram (EEG)

This is the most common test for epilepsy. A computer records the patient brain’s electrical patterns. If you have epilepsy, the EEG may show abnormal spikes or waves in the brain’s electrical activity patterns. Unfortunately, this test is not always conclusive because many people with epilepsy have normal EEGs in between seizures.

Imaging tests

An MRI and a CT scan are imaging tests that allow a doctor to view the brain. The scans can show scar tissue, tumors, or structural problems in the brain that may cause seizures or epilepsy. Imaging tests may not be done after a first seizure but they are recommended in many situations such as after a head injury.

Treatment (Part 7 of Is epilepsy genetic?)

Treatment initially consists of the administration of seizure suppressing drugs (anticonvulsants). In therapy-resistant cases of epilepsy, other methods such as epilepsy surgery are also used. Epilepsy has a variety of effects on the daily life of the affected person (such as suitability for certain professions or driving a car), which must also be taken into account in the treatment.

Medications

Most people can reduce the frequency and severity of seizures with anti-epliptic medications and some people see a stop in seizures completely. Many people can eventually discontinue medication in the absence of symptoms. You should always consult your doctor before stopping any medication. Usually epilepsy medications are started at a low dose and increased gradually. 

You should notify your doctor immediately if you notice new or increased feelings of depression, suicidal thoughts, or unusual changes in your mood or behaviors. Tell your doctor if you have migraines as they may prescribe one of the anti-epileptic medications that can prevent your migraines and treat epilepsy.

Some common side effects include:

  • Fatigue
  • Dizziness
  • Weight gain
  • Loss of bone density
  • Skin rashes
  • Loss of coordination
  • Speech problems
  • Memory and thinking problems

More-severe but rare side effects include:

  • Depression
  • Suicidal thoughts and behaviors
  • Severe rash
  • Inflammation of certain organs, such as your liver

In many cases, these medications are very effective and patients become seizure free.

Surgery

When medications fail to provide adequate control over seizures, surgery may be an option. In this surgery, a surgeon removes the area of the brain that’s causing seizures.

You may be a candidate for surgery if the seizures originate in a small, well-defined area of your brain and the area in the brain to be operated on doesn’t interfere with vital functions such as speech, language, motor function, vision or hearing.

Oftentimes, patients who have surgery can then take a reduced amount of medications. In a small number of cases, surgery for epilepsy can cause complications such as permanently altering your cognitive abilities. 

Alternative therapies

Other potential therapies to treat seizures have been used with various degrees of success. This options include:

  • Vagus nerve stimulation (a device similar to a pacemaker)
  • Ketogenic diet (You should consult a doctor if you or your child is considering a ketogenic diet as the patient may become malnourished if not eating properly. Supervision by a nutritionist is best)
  • Deep brain stimulation (implanted electrodes in the brain)

The United States National Institute of Neuorological Disorders and Stroke has many resources for patients, as well as the Center for Disease Control and Prevention.

If you liked this article, you should check out our other posts in the Nebula Research Library!