Frequently Asked Questions

Information obtained on this site should not replace medical advice from an expert. Please consult a neurologist for diagnosis and treatment. The following are some of the most frequently asked questions associated with KCNA2.

What is KCNA2?

KCNA2 is caused by a mutation on the KCNA2 gene, located on chromosome 1p13.

The University of Tubingen describes it this way, “The mutations disrupt the electrical balance in the brain in two ways.  In some patients, the flow of potassium is greatly reduced; while in others, it is raised enormously.  Both states can lead to hard to treat epileptic seizures.”

Early research looked at specific voltage-gated potassium (K*) channels to identify why a resting state of the cell is not achieved, thus causing a gain or loss of function.  Early research, conducted between 2013 and 2015 identified two phenotypes of the de novo KCNA2 mutation as a novel cause of epileptic encephalopathies associated with ataxia. By 2017, a third phenotype was identified.

KCNA2 Finding Cure

What causes KCNA2 mutation? Is it inheritable? 

The human genome contains 80 potassium channel genes of which 40 genes encode voltage-gated potassium channel pore-forming subunits that can be categorized into 12 subfamilies. The KCNA2 gene is located on chromosome 1p13 and encodes the voltage gated K+ channel Kv1.2 (OMIM_176262). There are four sequence-related potassium channel genes, identified as shaker, shaw, shab, and shal. KCNA2 belongs to the K 1 shaker subfamily of voltage-gated potassium channels within the brain.

The genes for the ion channels share important properties and are named to reflect them. “K” is the chemical symbol for potassium which is a positively charged ion. CN is an abbreviation for channel. The 2 means it is the 2nd member of the A subfamily which indicates that it is a voltage-gated potassium channel.

Being voltage-gated means that the channel opens and closes according to the charge in environment in the cell. The ions play a key role in a cell’s ability to generate and transmit electrical signals. Ion channels are pores in the cell membranes, around the outside of the cells, with gates that allow charged atoms (ions) to flow into and out of the cell (Gonzalez, 2012, Johnston, 2010,& Bocksteins, 2016).

When the KCNA2 gene is mutated, the channels do not function properly, causing a spectrum of disease that range from seizures in infancy, to developmental and epileptic encephalopathy.  These differences are likely based on the degree of dysfunction in the potassium channel.

Most genetic diseases are determined by the status of the two copies of a gene, one received from the father and one from the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease.

The abnormal KCNA2 gene can be inherited by either parent. The inherited mutation may be autosomal dominant (the mutation is found on one copy of the 22 pair of chromosomes), autosomal recessive (the mutation is found on both copies of the 22 pair of chromosomes), or X-linked (the mutation is found on the X chromosome). If the affected individual is a girl, the X chromosome linked to this mutation could be inherited from either the mother or father. If the individual is a boy, the X chromosome linked to this mutation is inherited from the mother since the father contributes only a Y chromosome to a male. In some situations, the mutation is not inherited from either parent. In this case, the mutation is referred to as “de novo”, or “new”, “from the beginning.”

What are possible symptoms of KCNA2?

  1. Seizures, tonic 
  2. Seizures, clonic 
  3. Multiple seizures daily at onset 
  4. Onset of seizures in infancy 
  5. Seizures are often unresponsive to treatment, particularly in early life 
  6. Generalized stiffening 
  7. EEG shows burst suppression pattern 
  8. EEG shows multifocal epileptic activity 
  9. Reduced posterior white matter volume (in some patients) 
  10. Delayed development (cognitive and/or motor) 
  11. Intellectual disability 
  12. Hypotonia (low muscle tone) 
  13. Dystonia (abnormal muscle tone) 
  14. Gastrointestinal issues (such as severe constipation or other distress) 

Variants may also occur de novo (not seen in either parent.)

Is KCNA2 a degenerative condition?

No, KCNA2 is not degenerative in nature.  However, depending on the severity of seizures and certain comorbidities, some individuals with KCNA2 may experience degenerative aspects. One example noted by parents is that when a child experiences hypertonia in their extremities, movement, strength, balance, and how effectively they can use their limbs may become more challenging over time.

How is KCNA2 diagnosed? 

Parents and caregivers usually observe early symptoms such as “staring spells”, irritability, difficulty sleeping, seizures, difficulties with balance (ataxia), delayed or labored speech, or some delay in the development of milestones.  When these concerns are addressed with the child’s pediatrician, further assessment is usually suggested, including genetic testing.  KCNA2 can be diagnosed through genetic testing.  The pediatrician may also request an EEG assessment.  An EEG is an electroencephalogram that records brain activity and can detect seizure activity.  The results of genetic testing, EEG patterns, and an observation of how the individual is functioning will determine the course of treatment related to medication and therapy.

Do children diagnosed with KCNA2 have a shortened lifespan?

Many parents who have children diagnosed with KCNA2 ask this question. At this time, there are no known cases of a child dying directly from having a KCNA2 mutation. However, it is possible that death can occur from symptoms common to KCNA2 such as a seizure, or an accident or fall caused by a seizure. Overall , children with any severe neurologic disorder are at higher risk of early death than the general population. Currently, there are several people diagnosed with KCNA2 who are in their 40’s and 50’s, illustrating that individuals diagnosed with KCNA2 do live well into adulthood.

What are the types of KCNA2 epilepsy?

KCNA2 is a gene involved in encoding the potassium channel Kv1.2-neurons. The three known types of KCNA2 mutation are the gain of function (hyperexcitability of the potassium channel), loss of function (electrical silencing of the potassium channel), or a combination of a gain and loss of function.

How will KCNA2 affect the development of my child?

Unfortunately, there is not one answer to this question. With the wide spectrum of KCNA2 cases, every child is different. Some people diagnosed with KCNA2 will have little to no impact on their development whereas others will be severely impacted. So far, research has shown that those with the loss of function variant will be least impacted, then the gain of function variant can see some very significant impairments, and finally, the mixed gain and loss of function variant typically displays itself with the most severe developmental and cognitive disabilities. Keep in mind that these are only generalizations from the small group of known KCNA2 cases. We are working to facilitate KCNA2 research that can more specifically answer these questions.

What is the range of developmental delay for KCNA2 patients? Across which areas of development does it effect? Does it change over time?

At the present time, there is not available data to support a quantitative answer to this question.  However, we do know that seizure activity in the brain interrupts concentration, attention, learning and sleep.  Therefore, it seems to take longer to learn a task and more repetitions may be necessary to learn new information.  As a result, learning across the board may be delayed in all or several areas.  The pace at which one can learn can change over time and there is no way to predict a pattern of changes.  One thing common to most KCNA2 patients is that they do improve over time.  These children can learn skills and improve with each skill in time.

Is there a treatment or cure for KCNA2? 

At this time, there is no cure and no FDA approved treatment for KCNA2. Current literature available about KCNA2 is often qualitative, and focused on identifying characteristics of those individuals diagnosed with KCNA2. Characteristics such as age, symptoms, specific prototype, and course of treatment are often highlighted.  Although this information creates a general picture of individuals diagnosed with KCNA2, clinical trials focused on specific treatment options are few and not readily available At this time.  There is a lot of work to be done for infants through adults who are diagnosed with KCNA2.  The KCNA2 Parent Group/Connection (FB) and the KCNA2 Epilepsy Global Connection web site serve as the foundation for parents and professionals from around the world to come together and promote awareness, education, research, and effective therapies for KCNA2 families.  Ultimately, we will find a cure

Have any single medications been found to be effective for all KCNA2 patients?

No. KCNA2 patients are on a wide range of medications, usually including multiple anti-seizure medications.  However, additional medications can be prescribed for other symptoms common to KCNA2, such as gastrointestinal or sleep issues.  Each patient may respond to medications differently, so medications and symptoms are closely monitored on an individual basis.  Hopefully, with more research, we can better understand the similarities and differences between KCNA2 gain, loss and mix of function.  This understanding may guide our choices of medications in the future, resulting in more effective seizure and symptom control.

How can I meet other families affected by KCNA2?

 If you have been diagnosed with KCNA2 or are a caregiver to someone who is, you can ask to join a private Facebook page called KCNA2 Epilepsy Parent Group/Connection.  Over 50 families from around the world have joined since the group was introduced in 2017.  On the site, you can read about other families.  They are listed under, “Stories, Around the Globe”- Our KCNA2 Family”.   As our website evolves, we will feature video meetings on specific KCNA2 topics. There you can connect with KCNA2 families from around the world. Eventually we will host a KCNA2 conference so parents and professionals can meet in person.

How do I help my healthy child to not feel jealous of the extra attention and things that my KCNA2 child experiences?

Do your best to identify and attend to the specific needs of all your children. You may need to restructure your time so you spend quality individual time with each of your children.  You can also teach your other children (as age appropriately as possible) what KCNA2 is and how they can support their sibling. This may help them gain a sense of control, understanding, and feel a part of a loving family who is supporting a family member.  Spend time listening to your “healthy” children so you can understand life from their perspective in terms of their experiences, opinions, emotions and needs.  This will ensure that they do not feel ignored. This may also prevent acting out behaviors that frequently occur when a child is in need of attention.

Is there any study/research currently running related to KCNA2 where I/my child can participate?

There are no significant research studies specific to KCNA2 at this time. Currently, there are “single case studies” that occur sporadically with one patient at a time to monitor a trial of a medication. The idea of creating this web site is to promote research specific to KCNA2 in an effort to develop a better understanding of the mutation and effective treatment.

What is Ataxia?

Movement that is shaky and unsteady.  This results from the brains inability to regulate the body’s strength, balance, posture, and smooth movements.

What does it mean when told the genetic mutation is ‘de novo’?

This means the mutation is “new”.  The chromosome abnormality found in the individual is ‘de novo’ when it is not inherited from either biological parent.  They can confirm this by testing each biological parent and find that neither parent has the abnormal chromosome found in the offspring.

What is an EEG? (Electroencephalogram)

EEG is an abbreviation for electroencephalogram.  It is a technique for studying the electrical current within the brain.  Electrodes are attached to the scalp.  Wires attach these electrodes to a machine which records the electrical impulses.  The results are displayed on a computer screen and can be printed out.  Different patterns of electrical impulses can denote various problems in the brain including different forms of epilepsy.  Some EEG’s are conducted for a few hours and some for a few days.  Depending on the goal of the EEG, data is collected to see how the electrical impulses in the brain look during sleep and while awake.  Some individuals are monitored after sleep deprivation.

What is a seizure?

Uncontrolled electrical activity in the brain that may cause the body to physically convulse.  There are several types of seizures including Absence Seizures (Petit Mal), Myoclonic, Tonic and Atonic (Drop Attacks) and Tonic-Clonic seizures (formally called Grand Mal seizures).

What is Epilepsy?

Epilepsy occurs when the neurons of the brain (nerve cells) fire electrical impulses at a rate of up to four times higher than normal.  This causes an “electrical storm”.  As a result of these  hyperactive electrical impulses, the brain seizes, interrupting normal brain activity.  Medication can be used to regulate the rate of electrical impulses in an attempt to stop seizure activity.

What is a Gene?

A gene is a very small structure inside almost every cell of the body.  They carry the instructions, or blueprints, that tell our body how to grow, develop, and function in terms of building necessary proteins.  These instructions result in the development of one’s characteristics such as eye color, height and blood type.  There are approximately 35,000 genes in the human body.

What is a Karyotype?

The chromosomal complement of an individual, including the number of chromosomes and any abnormalities.  The term is also used to refer to a photograph of an individual’s chromosomes.

What is Genetic Counseling?

This is an educational session to learn about genes, genetic conditions, heredity, and how genes are passed from one generation to another. Genetic counseling can explain how some conditions pose a risk for developing specific conditions and why some conditions are considered ‘de novo’.  Genetic counseling is an opportunity to learn about a genetic diagnosis and the meaning of a specific mutation.  It is a place to ask questions that pertain to treatment and management of a specific condition.

What is Genotype and Phenotype?

Genotype describes the genetic make-up of an individual, not their outward characteristics.  A phenotype is an observable trait of an individual such as their eye color, height, weight, or the presence or absence of a condition such as an intellectual impairment.

What is Hypertonia?

A condition marked by an abnormal increase in muscle tension and a reduced ability of a muscle to stretch.  HYPER relates to too much tension.

What is Hypotonia?

A condition marked by an abnormal decrease in muscle tension and an increase ability of the muscle to be floppy and stretch.  HYPO relates to not enough tension.

What is an MRI?

MRI is an abbreviation for Magnetic Resonance Imaging.  This is a radiology scan technique that uses magnetism, radio waves, and a computer to produce images of body structures.  The individual is placed in a very large circular tube and inserted into a magnet.  The magnet creates a strong magnetic field that combines with beams of radio waves that produces a signal that can be detected by the receiver portion of the MRI scanner.  The image is translated by a computer.  The resulting image can detect tiny changes and structures within the body.

Why is there almost NO information available about KCNA2?

KCNA2 was identified through genetic testing in about 2015. Research about this potassium channel related gene is in its infancy.  However, in the past two decades, research about seizures and epilepsy in general has evolved.  In that time, many separate organizations have been formed that focus on rare genetic mutations that cause seizures.  Collectively, these groups are referred to as RARE Epilepsies.  As awareness increases about KCNA2, so will research leading to effective treatments.