What is PCDH19 Epilepsy?

PCDH19 Epilepsy is a rare epilepsy syndrome with early onset seizures, cognitive and sensory delays, and behavioral problems. It is caused by a change or mutation of the PCDH19 gene found on the X chromosome.

The PCDH19 gene makes a protein (called protocadherin 19) which helps cells in the brain communicate. When this gene isn’t working right, the protein may be disrupted, not work right, or not work at all.

PCDH19 Epilepsy gene may affect just one person in a family through an accident in how the cells develop, or it can be inherited. Males who carry the gene change or mutation on their only X chromosome are typically not affected. In contrast, 90% of women who have the PCDH19 gene mutation on one of their two X chromosomes have the symptoms.

Who is affected?

About 1 in 10 girls that begin having seizures before the age of 5 may have PCDH19 Epilepsy. The features of PCDH19 can overlap or look similar to the features in Dravet Syndrome. It is estimated that there are between 15,000 and 30,000 people with PCDH19 Epilepsy in the United States. 

What do we know about seizures with PCDH19 Epilepsy?

  • Seizures usually start when a child is between 3 months to 3 years old.
  • Seizures may get less frequent in later childhood and adolescence.
  • Types of seizures seen may include: generalized tonic-clonic, tonic, clonic, complex partial, atypical absence, myoclonic, and atonic seizures.
  • The first seizure commonly happens when the child may have a fever. Later seizures occur without fevers.
  • Seizures tend to occur in clusters in the beginning and can vary a lot, lasting from days to weeks in some children. Status epilepticus (long or repeated seizures) can occur in children too.
  • A common seizure symptom in this type of epilepsy is the child screaming in fear.
  • Seizures can be difficult to control and usually take many anticonvulsant medication trials to treat and control the seizures.

How is the diagnosis of PCDH19 made?

Genetic testing on a blood sample can confirm the diagnosis of PCDH19 Epilepsy.

Electroencephalography (EEG) testing can be normal or in some cases show slowing on both sides of the brain and rare epileptiform discharges on testing when a person is not having a seizure.  Ictal EEG (EEG findings during a seizure) has been described as showing diffuse or bilateral frontal and temporal focal discharges.

Brain imaging with magnetic resonance (MRI scans) at onset of the seizures are typically described in reports as normal.

What are other PCDH19 symptoms?

  • Cognitive and intellectual disabilities can range from mild to severe. Some children may have normal development and cognitive function despite seizure clusters.
  • In some people, behavioral problems may include: aggression, attention problems (such as ADHD, ADD) anxiety, OCD, autistic spectrum features, depression, or psychosis.
  • Other symptoms noted in some children may include: fine and gross motor delays, language delay, sensory integration difficulties, sleep problems, low motor tone, constipation, or apnea with seizures.  

How is PCDH19 treated?

Seizure medication is the first line of treatment to prevent seizures and stop seizure clusters.

  • Some of the medicines used for this syndrome include:  benzodiazepines, levetiracetam, valproate, phenytoin, phenobarbital, and lamotrigine.  
  •  Seizures may be very difficult to control with medicines during the early years of life. They may respond better to medicines over time. For example, some people may be seizure free during adolescence and adulthood on one seizure medicine. .
  • Vagal nerve stimulation may be considered in some cases.

Who should be on your health care team?

The degree of disability and individual health needs varies for people with PCDH19 Epilepsy. If a child is diagnosed with PCDH19 epilepsy, they will require the support of a multidisciplinary team including a pediatrician and a pediatric neurologist/epileptologist, along with assistance from nursing, social work, and possibly also occupational, speech, and physical therapists and a psychiatrist.

Authored by: Elaine Kiriakopoulos MD | Drug Resistant and Rare Epilepsies Editor on 6/2015