Rett Syndrome and Epilepsy: Why Seizures Happen and What Helps

Rett syndrome is a rare genetic disease that affects brain development and the nervous system (the body’s system that controls movement, thinking, and communication). Most people living with Rett syndrome experience seizures at some point. Epilepsy (a neurological condition that causes repeated seizures) is one of the most common conditions that occurs alongside Rett syndrome.

Although seizures may not happen all the time, research suggests that up to 90 percent of people with Rett syndrome develop epilepsy at some point in their lives. For many people with Rett, anti-seizure medications (medicines that help prevent seizures) can help control seizures.

Read on to learn more about why seizures may occur and what treatments may help reduce seizures or lead to seizure remission (long periods without seizures) in people with Rett syndrome.

Why Seizures Happen in Rett Syndrome

Rett syndrome is a neurodevelopmental disorder. This means it changes how the brain grows, forms, and communicates with the rest of the body. The gene mutation (change) that most often causes Rett syndrome can lead to unusual electrical activity in the brain. Nearly all cases of Rett syndrome are caused by a spontaneous (new) mutation in the methyl CpG binding protein 2 (MECP2) gene. In people with Rett syndrome, this abnormal brain activity can affect abilities such as speaking, eating, moving, and performing other everyday functions.

Changes in brain activity can also trigger seizures. In some people, certain MECP2 mutations are linked to more severe symptoms, which may include more frequent or more severe seizures.

No Clear Cause

Brain imaging studies such as MRI can show patterns in brain structure or activity associated with Rett syndrome. However, no specific neurological brain scan findings can fully explain why seizures occur in Rett. The brain is extremely complex, and researchers are still learning how genetic changes like MECP2 mutations affect brain signaling and seizure risk.

In fact, about half of all people with epilepsy have seizures with no clearly identified cause. This group includes many people with epilepsy who do not have Rett syndrome.

How To Identify Seizures

Some behaviors and movements that are in Rett syndrome can easily be mistaken for a seizure. This can make it challenging for parents and caregivers to understand seizures in people with Rett syndrome.

Rett Syndrome Behavior Spells

People with Rett syndrome often have episodes of unusual or repetitive behaviors. Some medical professionals call these episodes “spells.” These events can sometimes look similar to seizures, which can make them difficult to tell apart.

Behavior spells that are not seizures may include:

• Twitching or jerking movements
• Repetitive hand movements
• Head turning
• Sudden leaning or falling forward
• Trembling
• Unusual eye movements, such as frequent blinking
• Sudden episodes of laughing or screaming
• Staring spells
• Pupil dilation (enlarged pupils)
• Breath-holding or hyperventilation (very fast breathing)

Because it can be hard to tell the difference between seizures and behavior spells in Rett syndrome, it’s important to talk with a doctor or neurologist (brain and nervous system specialist) if these episodes occur. To make a clinical diagnosis of epilepsy, doctors may recommend an electroencephalogram (EEG), a test that records the brain’s electrical activity.

An EEG can help doctors determine whether episodes are seizures before prescribing anti-seizure medications. Anti-seizure medications are used to treat seizures but will not help behavior spells that are not seizures. These medications can also cause side effects, so doctors usually want to confirm the diagnosis before starting treatment.

Seizure Risk by Age

Seizures can occur at any age in people with Rett syndrome, but the risk changes over time. Seizures are most common during childhood and early adolescence, and active epilepsy often peaks during the teen years. Studies also suggest that seizure rates are highest among children ages 7 to 12 years.

Seizures are less common in babies and very young children with Rett syndrome, and daily seizures are uncommon overall.

Seizure Risk During Childhood

According to Rett Syndrome Europe, the likelihood of seizures increases as children with Rett syndrome get older:

• About 1 in 3 children ages 2 to 5 will have seizures.
• About 2 out of 3 children ages 5 to 10 will have seizures.
• About 3 out of 4 children ages 10 to 15 will have seizures.

Seizure Risk After Childhood

After the teenage years, many people with Rett syndrome and epilepsy have fewer seizures, and the seizures they do have may be less severe. For some people, seizures may stop in adulthood or become easier to manage with anti-seizure medications.

However, a smaller group of people continue to have seizures into adulthood, and these seizures may be harder to control with treatment.

What To Expect in Seizures With Rett Syndrome

Several types of seizures can occur in people with Rett syndrome, and many people experience more than one type. One of the most common seizure types in people with Rett syndrome and epilepsy is generalized tonic-clonic seizures. However, other types of seizures can also occur.

General Tonic-Clonic Seizures

Sometimes called grand mal seizures, generalized tonic-clonic seizures affect the whole body. They are among the most common reported seizure types in people with Rett syndrome. They usually involve a sudden loss of consciousness (awareness) followed by body stiffening (the tonic phase) and rhythmic jerking or shaking movements (the clonic phase).

Focal Impaired Awareness Seizures

Focal impaired awareness seizures start in one area of the brain and affect awareness. They were previously known as complex partial seizures.

During a focal seizure with impaired awareness, a person may appear awake but not fully aware of what is happening around them. They may stare into space or not respond when someone speaks to them or calls their name. Some people also repeat certain movements, such as:

• Rubbing their hands
• Chewing or swallowing
• Walking in circles

After the seizure ends, the person may feel confused or may not remember the event.

Atypical Absence Seizures

Atypical absence seizures are most common in children. During this type of seizure, a child may stare into space and briefly lose awareness. They may remain still or have a small, repetitive body movement, such as eye blinking or lip smacking.

Unlike a typical absence seizure, atypical absence seizures often start and end more gradually and may last about 10 to 30 seconds. Loss of balance or falling can also occur during these seizures.

When To Seek Immediate Medical Attention

Seizures can be scary or dramatic, but most of the time, a seizure is not life-threatening. However, it’s important to seek medical attention if something happens that could be dangerous.

Call 911 or emergency services if a seizure has any of the following signs:

• It lasts longer than 5 minutes.
• Breathing or consciousness does not return after the seizure ends.
• Another seizure happens right after the first one.
• It occurs along with a high fever.
• It leads to an injury during the seizure.

Treatments for Epilepsy in Rett Syndrome

Medication is the most common treatment for epilepsy in people with Rett syndrome, and it helps control seizures for many people. According to the Epilepsy Foundation, about 2 out of 3 women over age 18 with Rett syndrome need anti-seizure medication to help manage seizures.

Anti-Seizure Medication

Anti-seizure medications are used to help prevent seizures or reduce how often they happen and how severe they are. In some cases, doctors may prescribe more than one medication at the same time. Different medications work in different ways, and some people respond better to certain medications or combinations of medications.

Anti-seizure medications that may be prescribed include:

• Carbamazepine
• Lamotrigine
• Levetiracetam
• Sulthiame
• Valproate

For children 2 and older, another medication called trofinetide (Daybue) may also be prescribed. Trofinetide is not an anti-seizure medication, but it is approved by the U.S. Food and Drug Administration (FDA) to treat Rett syndrome symptoms. Some small studies and case reports suggest it may also affect seizure patterns in certain people, but more research is needed to confirm this effect.

Diet and Other Treatments

Most of the time, seizures can be managed with anti-seizure medications. In some cases where medications do not work well enough, doctors may recommend other treatments.

One option is a ketogenic diet (often called the keto diet), which is a high-fat, very low-carbohydrate diet that can help reduce seizures in some people with epilepsy.

Another option is vagus nerve stimulation (VNS). VNS uses a small device implanted under the skin in the chest that sends mild electrical signals to the vagus nerve, which helps regulate brain activity. This treatment may help reduce seizure frequency for some people whose seizures are difficult to control with medication alone.

You Are Not Alone

A Rett syndrome diagnosis can feel overwhelming for families and caregivers. The process of getting a diagnosis and finding the right treatments can be emotionally challenging. Support and guidance can make a difference during this time.

People with Rett syndrome often receive care from several healthcare specialists, such as a neurologist, a cardiologist (heart specialist), a dietitian or nutrition specialist, a physical or occupational therapist, and an orthopedist (bone and joint specialist).

Connecting with others who understand Rett syndrome can also help. Your community on MyRettTeam is a place where people share experiences, ask questions, and support one another. Your healthcare team can also help guide you through treatment decisions and ongoing care.

Join the Conversation

On MyRettTeam, people share their experiences with Rett syndrome, get advice, and find support from others who understand.

How have you succeeded in managing seizures? Let others know in the comments below.