PCHD19 Genetic Mutation and Epilepsy

By: Andrew Yee

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PCHD19 Epilepsy

PCHD19-epilepsy is a type of epilepsy caused by a mutation of the PCDH19 gene on the X chromosome. The PCDH19 gene results in epilepsy by encoding the protein protocadherin 19. PCDH19-epilepsy begins in the first year of life and mainly affects girls. Boys may also be affected, but it is much less common given that the gene is tied to the X chromosome (Children’s Hospital of Philadelphia, 2020).


All children with PCHD19-epilepsy have a mutation in the PCDH19 gene. The PCHD19 gene encodes the protein protocadherin, which is responsible for cell communication. Mutations to this gene affect the communication of neurons with one another through cellular interference, leading to epilepsy and associated neurodevelopmental conditions (Children’s Hospital of Philadelphia, 2020). Since the PCHD19 gene is located on the X chromosome, the extent of the mutation varies by sex. Since a male has an XY genotype and a female has an XX genotype, females are more commonly affected, while males with one copy are typically unaffected. Approximately ninety-five percent of PCDH19-epilepsy patients are females, and five percent are males (Children’s Hospital of Philadelphia, 2020).


Symptoms range from a variety of cognitive, psychiatric, and physical challenges:


The course of development for intellectual disabilities usually occurs in one of three paths:

  • Normal development with regression from seizures
  • Regular development and intellectual ability from birth, without regression
  • Delayed from birth and remains delayed into adulthood

(PCDH19 Alliance, 2022)


Psychiatric conditions and symptoms include:

  • Autism spectrum disorder (around 60% diagnosis)
  • Behavioral problems
  • Aggression
  • Anxiety
  • Obsessions

In adolescents and adults, depression, bipolar disorder, schizophrenia, psychosis, and other mental illnesses have been reported (PCHD19 Alliance, 2022).


The following physical symptoms can be present with PCDH19:

  • Ictal apnea
  • Sleep disturbances
  • Motor deficiencies
  • Language delay
  • Sensory issues
  • Dysautonomia
  • Hypotonia (decreased muscle tone)

(PCDH19 Alliance, 2022)

Seizure types:

The following types of seizures that occur with PCDH19 are:

  • Generalized tonic-clonic seizures
  • Focal-impaired awareness seizures
  • Tonic seizures
  • Complex partial seizures
  • Atypical absence seizures
  • Atonic seizures (Atonic drop)
  • Myoclonic seizures

                                                    (Children’s Hospital of Philadelphia, 2020)

Seizure Clusters:

The most common feature of PCHD19-epilepsy is seizure clusters. Seizure clusters are the occurrence of seizures that come in heavy, grouped amounts across days or weeks and do not respond well to medication (Children’s Hospital of Philadelphia, 2020).

  • The first seizure occurs between three months and three years of age
  • Starts arising through illness and becomes triggered randomly
  • Often drug-resistant and hard to control
  • About seventy percent experience of motor skills, hearing, and cognitive functions post-seizure

                                                                                              (Children’s Hospital of Philadelphia, 2020)


The appearance of seizures during the first year of life produced by an illness or fever (febrile seizures) may suggest PCHD19 epilepsy. The occurrence of many seizures in a short time frame, followed by a break from seizures, may also suggest PCHD19 epilepsy.

The following tests may be conducted to confirm a diagnosis of PCHD19:

  • Genetic testing:  A DNA test can determine if the PCHD19 gene is mutated
  • EEG (electroencephalogram): often used to track electrical activity in the brain by measuring the electrical impulses in the brain.
  • MRI (magnetic resonance imaging): a medical device that creates images of your organs and tissue throughout your body. It uses magnets and radiofrequency to create an image. An MRI is a painless procedure.

(Children’s Hospital of Philadelphia, 2020)


Treatment for PCHD19-epilepsy will depend on the type and severity of seizures and associated neurological features:

  • Anticonvulsant medications
  • Rescue therapies for seizure clusters
  • Dietary therapy
  • Vagus nerve stimulation (VNS) or Responsive neurostimulation (RNS)

(Children’s Hospital of Philadelphia, 2020)

Family support is a crucial part of treating epilepsy. Parents and caregivers must be aware of symptoms, seizures, and how to respond. Taking care of your child can be extremely tiring when they are battling a chronic illness like epilepsy. To manage life and treatments, families can seek psychosocial support, develop an appropriate education plan, and access available community resources. Genetic counseling is also recommended.

Additional therapies such as physical, occupational, and speech therapy may be beneficial in helping to treat cognitive issues and developmental delays. Talk with your neurologist or epileptologist to see if this is an option.

                                                                                                  (Children’s Hospital of Philadelphia, 2020)  


In conclusion, PCHD19 epilepsy is caused by a mutation in the PCHD19 gene. The mutation affects the protein protocadherin 19, creating cellular interference between brain neurons. The most common symptom of PCHD19 is seizure clusters. Treatment for PCHD19 and the corresponding neurological functions will vary based on the severity.  Still, it is generally treated with a wide range of therapies, anticonvulsant medications, and devices.


Children’s Hospital of Philadelphia (2020). PCHD19 Epilepsy. Children’s Hospital of Philadelphia. Retrieved from: https://www.chop.edu/conditions-diseases/pchd19-epilespy.

PCHD19 Alliance (2022). What is PCHD19? PCHD19 Alliance. Retrieved from: https://www.pchd19info.org/pchd19-epilepsy.                         

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