Updated: Apr 25, 2021
The identification of KCNA2 began with research of voltage-gated potassium channels (VGKCs). These channels are specific for potassium and sensitive to voltage changes in the cell’s membrane. Voltage changes occur in the cell’s membrane as cells communicate normally. Cells communicate when an active cell sends an electric signal from the cell body down the axon to a resting neuron cell. Once the resting cell receives the electric signal, it becomes active. After the signal is complete, potassium channels, along with other specific ion channels, play a crucial role in returning the activated cell neuron to its resting state. A resting state is necessary for the cell to stabilize before reactivating. This process repeats over and over as cells continue to communicate with each other. Seizures occur when a disruption in the flow of potassium occurs, causing the active cell to remain active, unable to return to its resting state. Early research, between 2013 and 2015, of specific voltage-gated potassium (K*) channels found that a mutation in the voltage-gated channel KCNA2, is responsible for the disruption in the flow of potassium. The KCNA2 gene is located on chromosome 1p13 and encodes the voltage-gated K+ channel Kv1.2 (OMIM_176262). A mutation of KCNA2 interrupts the resting state of the cell, causing a gain or loss of function in potassium flow. Early research identified two phenotypes of the de novo KCNA2 mutation. In one, the flow of potassium is greatly reduced (loss of function), while in the other, the flow of potassium is raised enormously (gain of function). By 2017, a third phenotype was identified. This was a mixed flow pattern (gain and loss of function) where the potassium flow function is inconsistently both greatly reduced and greatly raised. All three phenotypes of KCNA2 can result in very-difficult-to-treat seizures and ataxia.
KCNA2 Syndrome Clinical Features
All three phenotypes of the KCNA2 mutation cause a number of neurodevelopmental challenges, with a broad range of severity. Multiple seizure types, intellectual delays, ataxia, general coordination problems, speech difficulties, and irregular sleep patterns are common, but not universal to everyone with the diagnosis. Life-threatening episodes of seizures are not uncommon. Clinical features of KCNA2 continue to be identified, clarified and understood through early research of this relatively newly discovered genetic mutation. The literature suggests that there are less than 300 confirmed cases of KCNA2 as of 2019.
Get to Know KCNA2epilepsy.org
We are a new organization who launched the KCNA2 Parent Connection Facebook page (private) in 2017 and will launch our web-site (KCNA2epilepsy.org) in December of 2020. We will also apply for 501© 3 status in the United States in 2021. Our mission is to educate, support and connect with individuals and families around the world. Together we can advocate locally and globally for research, treatment, and a cure for this rare epilepsy.
Short- and long-term goals include:
1. Provide information and resources to families.
2. Identify and connect with researchers, clinicians and professional bodies.
3. Identify research projects and treatments around the globe.
4. Connect with other KCNA2 groups (if available) to coordinate awareness-raising and resource sharing.
5. Raise awareness of KCNA2 with public and health professionals as well as educators.
6. Promote fundraising for KCNA2.
7. Work with relevant government departments and rare disease entities ensuring our work aligns with providing access to treatments when they become available.
I am especially proud of ...
The (first ever) KCNA2 family support group that was initiated in March of 2017, via Facebook. In only three years, we have connected with over 60 families from around the world who are affected by KCNA2 epileptic encephalopathy. Together, we have created a private, solution-focused community who share their challenges and successes as caregivers, navigating the somewhat unfamiliar worlds of medications, seizures, therapies and educational options available for their child. While we learn together, we help to educate many physicians, therapists and educators who have never before heard about KCNA2. Together, we share information about what seems to work and not work with regard to getting involved with research opportunities, treatment options and quality of life solutions. Collectively, we understand how stressful it is to watch our children experience life threatening seizures. I am proud to say that we have managed to maintain an active group who, despite stress and disappointments, continue to ask difficult questions, contribute honest answers, and support each other in kind, loving and respectful ways. We appreciate our private forum in which we communicate with each other. However, we also recognized a need for a public forum. A public forum, via a web site, will allow us to raise global awareness of KCNA2. By December, 2020, we will launch the website kcna2epilepsy.org. The goal of our site is to provide information, support and resources to families around the world. We hope to connect with medical and scientific experts, neurologists, therapists, educators, and biopharmaceutical companies to advance research and treatment available for individuals diagnosed with KCNA2. Our organization is also inquiring about 501© 3 non-profit status in the United States. Donations will focus on awareness-raising efforts and advancing research.
Excited to REN because...
Participating with REN will allow us an opportunity to collaborate with others who also strive for more advocacy, research opportunities, and effective treatment interventions pertaining to a rare epilepsy diagnosis. Collectively, we can network, share our wisdom and many resources available to enhance all of our goals.
My journey and motivation...
My daughter Giana is 23 years old. She was not diagnosed with KCNA2 until she was 17. Until then, she was tried on many medications to control seizures. Not knowing the cause of her seizures, many anti-epileptic medications (over 15) were tried, and failed. Receiving a diagnosis has helped to streamline her treatment, but control is far from perfect. A diagnosis also allowed her to become involved in a single case study targeting her specific KCNA2 phenotype. Throughout all of this, Giana has developed into a beautiful young lady. She is smart, pleasant and kind with a sense of humor others gravitate toward. She enjoys guitar and banjo and loves animals, especially her dogs. She continues to pursue her dream of becoming a dog trainer. My motivation is to help others become aware, understand, and participate in the healing of individuals who have a rare epilepsy diagnosis. Although their diagnoses are rare, they are not. Children and adults with rare epilepsies are more like others than not. They enjoy friends, activities and adventure. They appreciate it when someone listens and allows them to make choices. They understand, feel and express love. Connecting with groups like REN will lead to effective seizure control and will help individuals with rare epilepsies to achieve their goals and enjoy life with their family, friends and community (just like other kids their age do). When I ask Giana, what motivates her she says, “Because you believe in me.” Hearing that from her will motivate me forever.
In The New Normal, psychologist Nancy Musarra shares her challenges and triumphs as a mother of a child with special needs. Having interviewed hundreds of people—from parents to caregivers—who have walked the same path, Dr. Nancy shares their stories and reflections. Collectively their wisdom forms the foundation of The Seven Things You Need to Know to be prepared for your journey.
By Nancy Musarra