SCN2A Awareness Day: Q&A with Epilepsy Expert M. Scott Perry, M.D.
Today is SCN2A Awareness Day, a day recognizing a rare cause of epilepsy, intellectual disability, and autism. The SCN2A gene is found on chromosome 2 position 24.3, thus the significance of 2/24.
To help raise awareness of this rare genetic cause of neurodevelopmental disease, M. Scott Perry, M.D., medical director of neurology and director of the Genetic Epilepsy Clinic at Cook Children’s, shares basic information about the disorder and exciting advancements towards treatment for this rare disease.
What do SCN2A-related disorders look like?
Children with genetic variants in SCN2A can develop early onset epilepsy with various levels of severity. SCN2A was first discovered as a cause of benign familial neonatal infantile seizures (BFNIS), a syndrome that often occurs in multiple family members. These children can develop seizures as newborns or infants, but can develop normally with good seizure control.
Later, SCN2A was discovered as a cause of infantile spasms and other early onset severe epilepsies of childhood, the so-called early infantile epileptic encephalopathies. The gene has also been linked to Ohtahara Syndrome, Dravet Syndrome, Migrating Partial Epilepsy of Infancy and West Syndrome amongst others. In addition, SCN2A variants are a major cause of intellectual disability, schizophrenia, and autism which may occur without associated epilepsy. A variety of other medical conditions may be present in people with SCN2A-related disorders, including sleep problems, cerebral palsy, and movement disorders to name a few.
What is the cause of SCN2A-related disorders?
SCN2A is a gene which makes a sodium channel found primarily in the nerve cells that generate electricity. Two issues can occur with SCN2A. The first is a change in the gene which causes a gain of function – a change that allows too much sodium to enter the nerve cell and thus increases electricity – often presenting with epilepsy as a main symptom.
For others, SCN2A variants cause a loss of function – a change that decreases sodium entering the nerve cell and thus decreases electricity – more often presenting with autism and intellectual disabilities. Many mutations in SCN2A are de novo, meaning they occur spontaneously and were not inherited from the parents. This is often the case in more severe disease presentations. There are instances where SCN2A may be inherited from a parent and this is more commonly seen in benign presentations such as BFNIS.
How are SCN2A mutations diagnosed?
Often, genetic testing can diagnose SCN2A mutations. The Behind The Seizure program provides free testing for children in the U.S. under the age of 8 years.
Magnetic resonance imaging (MRI) scans are often normal and electroencephalogram (EEG) findings may vary.
Is there a treatment for SCN2A-related disorders?
While there is not yet a cure for SCN2A-related disorders, a significant amount of research is leading to exciting new therapies. Certain traditional sodium channel seizure drugs (for example, phenytoin, lamotrigine) have demonstrated more favorable responses for seizure control in select patients (often gain of function), while in others, sodium channel drugs may aggravate seizures.
New drugs are being developed that specifically target the abnormal channel produced by SCN2A. These treatments may provide more precise control of the channel without disrupting the function of other sodium channels like many traditional sodium channel seizure drugs. This may result in better seizure control with less side effects.
Potentially most exciting is the development of genetic approaches to therapy, treatments that don’t just treat symptoms, but aim to correct the genetic abnormality. Antisense oligonucleotides (ASO) are small pieces of genetic material that can be given to help increase or decrease production of SCN2A. This approach has been used in other genetic conditions (spinal muscular atrophy and Dravet syndrome) with success and represents a promising therapy for SCN2A disorders as well. This is just one of several genetic approaches to therapy on the horizon.
Where can you find more information about SCN2A disorders?
For more information about SCN2A and SCN2A Awareness Day, visit www.scn2a.org. The SCN2A Foundation serves as an excellent resource for information about SCN2A related disorders and helps connect a community of people living with these rare conditions. The site provides updates on SCN2A research as well.
Learn More about Cook Children’s Epilepsy Program
Cook Children's Comprehensive Epilepsy Program is one of the leading and most advanced pediatric epilepsy programs in the country. The National Association of Epilepsy Centers recognizes Cook Children's Comprehensive Epilepsy Program as a Level 4 Pediatric Epilepsy Center. Level 4 epilepsy centers have the professional expertise and facilities to provide the highest level of medical and surgical evaluation and treatment for patients with complex epilepsy.
Our program coordinates the skills of a highly specialized team of experts across neurosciences and Cook Children's Health Care System. This team is made up of epileptologists, neurologists, neurosurgeons, neuropsychologists, nurse specialists, EEG technologists, nutritionists, nurse educators, social workers and Child Life specialists, all working together to ensure children with epilepsy receive the most accurate diagnosis and advanced treatment available.
More than 13,000 infants and children with seizures are treated at Cook Children’s each year. Annually, we perform more than 6,000 EEGs and 40-50 epilepsy surgeries, making Cook Children's Comprehensive Epilepsy Program one of the busiest pediatric epilepsy centers in the nation. And with specialized diagnostic tools, like our MEG, the newest generation of advanced imaging technology is now available to even our youngest patients.
For more information, visit our website.
I joined the Neurosciences Program of Cook Children's in 2009 as a pediatric epileptologist, then served as the Medical Director of the Epilepsy Monitoring Unit and Tuberous Sclerosis Complex clinic before assuming the role of Medical Director of Neurology in 2016. My clinical and research interests focus on the treatment of childhood onset epilepsy, specifically those patients with uncontrolled epilepsy or those for which the cause has not been determined. I have an intense interest in the use of surgical therapies to treat and cure epilepsy. The majority of my research has investigated the use of multimodal imaging techniques to localize seizure onset, as well as the description of patient and disease characteristics that predict favorable outcomes from surgical therapies. The pool of candidates which may benefit from surgical therapy continues to expand and I came to Cook Children's specifically because the staff of the Epilepsy Monitoring Unit and Comprehensive Epilepsy Program were dedicated to improving the care of children with epilepsy through cutting-edge techniques, research, and concern for their patients' wellbeing.
In addition to my interest in surgical therapies, I care for a number of patients with epilepsy secondary to genetic cause. As our understanding of epilepsy has progressed and the sophistication of genetic testing has evolved, many new gene mutations have been discovered which lead to epilepsy. These syndromes often have certain characteristics for which treatment choices may be altered and outcome changed based on understanding the genetic mutation present. Many patients may have suffered years with uncontrolled epilepsy of unknown cause, but upon reevaluation a diagnosis may be made. With these patients in mind, I created the Genetic Epilepsy Clinic at Cook Children's, along with my partners in genetics, to improve the diagnosis, understanding, and treatment of children with these rare conditions.
Outside of my clinical and research interests, I serve on a number of local, national, and international committees dedicated to improving the care of childhood onset epilepsy. My free time is often spent with my wife and two daughters- usually at one of their cheer competitions. I enjoy music of all types as well as collecting art, especially pieces related to the blues and my childhood home of the Mississippi Delta.