Genetic generalized epilepsy (GGE), previously known as idiopathic generalized epilepsy, is a group of four types of epilepsy with genetic causes. GGE is common and accounts for 15 percent to 20 percent of all cases of epilepsy.

The International League Against Epilepsy defines four subtypes of GGE:

• Childhood absence epilepsy (CAE)
• Juvenile absence epilepsy (JAE)
• Juvenile myoclonic epilepsy (JME)
• Epilepsy with generalized tonic-clonic seizures alone (EGTCA)

Each subtype of GGE is characterized by the age of onset and the main seizure type it causes. GGE causes specific types of generalized-onset seizures (which involve both sides of the brain):

• Absence seizures — A brief period where the person stares into space and is unresponsive
• Myoclonic seizures — Sudden, brief, uncontrollable muscle jerks without loss of consciousness
• Tonic-clonic seizures — Whole-body seizures with loss of consciousness, stiffening, and then jerking of muscles (previously called grand mal seizures)
• Myoclonic-tonic-clonic seizures — Muscle jerks followed by a tonic-clonic seizure

Many people with GGE experience more than one type of seizure at some point.

Although the different types of GGE affect people of different ages and cause different types of seizures, they all have these features in common:

• Seizures are generalized, involving both sides of the brain.
• Electroencephalogram (EEG) readings show abnormal “generalized spike-and-wave” or “polyspike-and-wave” patterns.
• No other causes for the seizures can be identified, such as structural brain abnormalities.

GGE usually occurs in healthy individuals who have no other neurological disorders, but it may occur alongside depression, anxiety, attention-deficit/hyperactivity disorder (ADHD), and learning difficulties. GGE is usually not linked with developmental abnormalities, except in cases of specific genetic syndromes.

Causes of Genetic Generalized Epilepsy

All forms of GGE are believed to have a genetic cause, but only some of the specific genetic causes have been identified. GGE is associated with mutations (variants, or changes) of individual genes as well as chromosomal abnormalities. These genetic changes can be either inherited mutations (passed down through families) or spontaneous (new) mutations.

Unlike some genetic diseases, such as hemophilia A (a rare bleeding disorder), GGE is not usually caused by mutations in a single gene. It’s not fully understood how genetic mutations cause GGE, but the process is believed to involve a perfect storm of genes interacting with one another to cause disease. GGE can sometimes run in families, with multiple first-degree relatives (parents, children, and siblings) having related generalized seizure disorders.

Chromosomal Abnormalities

Some types of GGE are linked to specific chromosomal issues. Human DNA is organized into 23 pairs of chromosomes. Changes such as deleted (missing) or extra (duplicated) parts of these chromosomes can lead to genetic conditions like Down syndrome and Klinefelter syndrome, which may also increase the risk of epilepsy and seizures.

Gene Mutations

Specific gene variants are also connected to GGE. Although scientists have identified some of these genes, many remain unknown. Genes linked to GGE often play a role in how brain cells function, particularly ion channels and GABA receptors. Ion channels are pathways in neurons (brain cells) that move tiny particles like sodium and calcium in and out, producing electrical signals. If a gene mutation causes these channels to work improperly, it can result in abnormal electrical signals in the brain, triggering seizures.

GABA — short for gamma-aminobutyric acid — helps the brain control activity by calming neurons. This chemical attaches to GABA receptors, which act like locks that only open when GABA fits in. When these receptors don’t work right because of a mutation, brain activity can become unbalanced, leading to seizures.

Diagnosis of Genetic Generalized Epilepsy

Diagnosing GGE involves collecting detailed personal and family medical histories. For children, this information is often provided by a parent or caregiver. Doctors also perform a physical exam and an EEG. Observing how seizures look and occur is important for making an accurate diagnosis. Parents, caregivers, or other witnesses typically describe the seizures, and video recordings of episodes can be especially helpful.

Neurological test results are usually normal in people with GGE. Brain imaging studies, such as CT scans and MRIs, and genetic testing aren’t usually used to diagnose GGE. These tests might be used, however, if unusual features, such as intellectual disabilities or uncommon types of seizures, suggest other causes of epilepsy.

EEG testing helps determine a person’s type of epilepsy disorder. An EEG uses small electrodes on the scalp to measure the brain’s electrical activity. For people with GGE, an EEG done during a seizure typically shows abnormal activity on both sides of the brain.

Sleep deprivation before an EEG can make these patterns more noticeable, and some abnormal activity might even show up during sleep. For some people with GGE, triggers such as flashing lights and patterns can cause seizures. Some types of seizures can be provoked by hyperventilation (rapid breathing).

Treatment of Genetic Generalized Epilepsy

The main treatment for GGE is broad-spectrum anti-seizure medications, which are used to treat all types of seizure disorders. GGE doesn’t typically respond to narrow-spectrum, or more specific, anti-seizure medications. Drugs that affect sodium channels and GABA receptors can make seizures worse.

Commonly prescribed medications for GGE include:

• Divalproex sodium (Depakote)
• Lamotrigine (Lamictal)
• Levetiracetam (Elepsia XR, Keppra, Roweepra, Spritam)
• Topiramate (Eprontia, Qudexy XR, Topamax, Trokendi XR)
• Zonisamide (Zonegran)

GGE may require lifelong treatment with anti-seizure medication. Childhood epilepsy syndromes may resolve as a person gets older but sometimes evolve into other types of GGE.

A ketogenic diet can help reduce seizures in children with GGE, especially if medications don’t adequately control seizures. The diet restricts carbohydrate (sugar) intake and increases fat intake to maintain high levels of ketones (products of broken-down fat) in the blood. Although the ketogenic diet is effective, this very restricted eating plan can be hard to maintain.

Types of Genetic Generalized Epilepsy

There are several types of genetic generalized epilepsy.

Childhood Absence Epilepsy

CAE usually begins between ages 2 and 12 and makes up about 18 percent of cases of childhood epilepsy. CAE causes absence seizures, which are short episodes in which a person may suddenly stop what they’re doing, appear to be staring blankly, and then seem briefly confused when emerging from the seizure. Absence seizures usually last less than 10 to 15 seconds but may last longer.

Children with CAE have one or more seizures every day and may also have generalized tonic-clonic seizures, which cause a loss of consciousness and convulsions. CAE resolves by adolescence in most cases (about 60 percent), but it can evolve into another type of GGE.

Several mutations in GABA receptor genes (GABRG2 and GABRA1) have been linked to CAE. A chromosomal abnormality called 15q13.3 microdeletion syndrome, which causes a variety of physical and developmental defects, is associated with CAE. Another gene, SLC2A1, is associated with glucose transporter 1 deficiency syndrome. This disorder prevents glucose (blood sugar) from entering the brain, leading to various neurological symptoms, including seizures that begin in infancy or very early childhood.

Juvenile Absence Epilepsy

JAE is very similar to CAE but less common. JAE affects children and young adults between ages 8 and 20 and rarely begins later in adulthood. Absence seizures in JAE are less frequent than in CAE (occurring less than once a day), last slightly longer (5 to 30 seconds), and involve only partial loss of awareness.

More than 90 percent of people with JAE also have generalized tonic-clonic seizures. CAE can evolve into JAE as a person gets older, but unlike CAE, JAE usually requires lifelong treatment with anti-seizure medications.

Mutations linked with JAE are seen in the GABRG2, GABRA1, and SLC2A1 genes (those also linked to CAE), as well as CACNA1A, a calcium channel subunit gene. Calcium channels are an important type of ion channel that’s involved in allowing neurons to “fire,” or produce electrical discharges.

Juvenile Myoclonic Epilepsy

JME, a common type of GGE, accounts for almost 10 percent of all cases of epilepsy and usually starts between ages 8 and 40. Up to 15 percent of cases of JME evolve from CAE. JME causes myoclonic seizures — sudden, brief, uncontrollable muscle jerks that affect a single muscle or muscle group but don’t cause a change in awareness or consciousness.

Myoclonic seizures in JME usually occur within an hour of waking or when a person is tired or sleep-deprived. About one-third of people with JME have absence seizures, which tend to be milder and less frequent than those seen with CAE or JAE. More than 90 percent of people with JME experience generalized tonic-clonic seizures, sometimes after a series of progressively worsening myoclonic seizures. JME usually requires lifelong treatment with medication to prevent seizures.

JME is linked with mutations in several different genes, including:

• GABRA1 and GABRD
• CLCN2, a chloride channel gene
• CACNB4 and EFHC1, calcium channel genes

JME is also linked to chromosomal abnormalities including microdeletions 15q13.3 and 15q11.2 and microduplication 16p13.11.

Epilepsy With Generalized Tonic-Clonic Seizures Alone

As the full name implies, EGTCA causes generalized tonic-clonic seizures without any other types of seizures. This GGE syndrome can occur in people ages 5 to 40, but 80 percent of cases begin in a person’s 20s. The frequency of seizures can vary widely. Some people may experience fewer than one seizure per year, while about 20 percent of individuals have seizures more than once a month. In some cases, this syndrome evolves from CAE.

Generalized tonic-clonic seizures involve the whole body and typically start with a tonic phase, during which muscles suddenly stiffen, followed by a clonic phase, marked by rhythmic jerking or twitching. These seizures also cause a loss of consciousness and almost always occur within two hours of waking up. However, triggers such as fatigue, lack of sleep, and alcohol consumption can make seizures more likely to occur. This type of epilepsy requires lifelong treatment.

Epilepsy with generalized tonic-clonic seizures alone is strongly linked with a family history of seizure disorders. About 20 percent of people have a family history of this type of seizure alone, and about 10 percent have a family history of febrile seizures (brought on by fever). The CLCN2 gene is also associated with this type of GGE.

Outlook for Genetic Generalized Epilepsy

A person’s outlook with GGE depends partly on their subtype:

• CAE often improves with age, though in some cases, it may develop into other types of genetic generalized epilepsy.
• JAE and JME can also improve over time but may require lifelong treatment.
• EGTCA usually requires lifelong treatment, although seizures may be infrequent.

Accurate diagnosis of GGE is essential to determine the appropriate treatment. GGE typically responds well to treatment with broad-spectrum antiepileptic drugs, but using the wrong medications can make symptoms worse. It’s important to work closely with your health care provider to make sure you have the right treatment plan for your needs.

Talk With Others Who Understand

MyEpilepsyTeam is the social network for people with epilepsy. On MyEpilepsyTeam, more than 123,000 members come together to ask questions, give advice, and share their stories with others who understand life with epilepsy.

Are you or someone you care for living with a type of genetic generalized epilepsy? Share your experience in the comments below, or start a conversation by posting on your Activities page.