Authors: Dorottya B. Kacsoh, University of Central Florida College of Medicine   
Alison L. Christy, MD, PhD, Providence Pediatric Neurology at St. Vincent Medical Center—Portland, Oregon  

Reviewed: October 2023 

SUMMARY 

DEPDC5-related epilepsies are a diverse group of epilepsies. They are caused by a variation in the DEPDC5 gene. They typically run in families. The diagnosis is made by genetic testing. Most patients will need to take more than one anti-seizure medication.  

Disorder Overview

DESCRIPTION

There are many different epilepsy syndromes related to variants in DEPDC5. The most common is called familial focal epilepsy with variable foci (FFEVF). However, other types may occur.  

In most of the associated conditions, seizures tend to be focal. This means they begin in one part of the brain. Most children have average intelligence. However, mild to severe intellectual disability is possible. 

SIGNS AND SYMPTOMS

Familial Focal Epilepsy with Variable Foci (FFEVF) 

A “focus” is an area in the brain where cells develop differently. This causes:  

• Seizures  
• Abnormal electrical activity  

When cells in this area fire at the same time, a focal seizure can occur. (This used to be called a partial seizure. A focal seizure with impaired awareness used to be called a complex partial seizure.) Sometimes this seizure spreads to the rest of the brain. This is called secondary generalization.  

Focal seizures are the main seizure type in FFEVF. Focal seizures can look different. It depends on which part of the brain is involved in the seizure.  

The focus can be located in different areas of the brain in different family members who have FFEVF. This can cause different focal seizure types among family members. This occurs despite there being a variation in the same gene.  

Seizures start anywhere from infancy to adulthood.  

CAUSES

DEPDC5-related epilepsies are caused by a variation in the DEPDC5 gene. This gene normally makes it harder for new cells to be created. In DEPDC5-related epilepsies, the variation causes too many cells to be present in certain areas of the brain.  

DEPDC5-related epilepsies typically run in families. They are inherited in the autosomal dominant pattern. This means that only one variant copy of DEPDC5 needs to be present to cause epilepsy. However, some people can have the variant and not show symptoms. Males and females are equally affected.  

LABORATORY INVESTIGATIONS

The following tests can help diagnose DEPDC5-related epilepsies: 

TREATMENT AND THERAPIES

About 50% of patients have seizures that are not completely controlled with medications. Most patients will need multiple medications.  

Some children have a single area of the brain that is causing seizures. This is also called a “focus.” These children may benefit from epilepsy surgery. Surgery may involve:  

• Removing the focus that is causing seizures. 
• Vagus nerve stimulation (VNS). A device is implanted under the skin. It is connected to the vagus nerve in the neck. The nerve is stimulated on and off, regardless of whether there is abnormal electrical activity in the brain.  
• Responsive neurostimulation (RNS). Electrodes are placed directly into the focus in the brain. The device sits within the skull. The device will detect abnormal electrical activity and stop it before it becomes a seizure. 

Even if a focus cannot be found, VNS therapy may still be beneficial. Please see the Surgery section on the Epilepsy page in our CNF directory for more information. 

OUTLOOK

Children typically have average intelligence. Some may have mild intellectual disability. Children who have infantile spasms often have severe intellectual disability. Some children may have autism spectrum disorder or psychiatric disorders. For example, they may have ADHD, anxiety, or depression.  

In some studies, DEPDC5 variants are found in up to 10% of cases of Sudden Unexpected Death in Epilepsy (SUDEP). This may be because seizures in DEPDC5 tend to occur at night and be resistant to medications. Please see the SUDEP page on our CNF website for more information

RELATED DISORDERS

Related disorders include: 

• Familial focal epilepsy with variable foci (FFEVF) 
• Sleep-related hypermotor epilepsy (SHE) 
• Infantile spasms 
• Autosomal dominant epilepsy with auditory features 
• Familial mesial temporal lobe epilepsy 

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