SCN2A: What You Need To Know About This Rare Cause of Epilepsy
Cook Children’s Recognizes SCN2A Awareness Day
SCN2A is a gene found on chromosome 2 position 24.3 and thus 2/24 is celebrated as SNC2A Awareness Day worldwide. A rare cause of epilepsy, SCN2A mutations have also been discovered as a cause for intellectual disability and autism. To raise awareness of this rare genetic cause of neurodevelopmental disease, Dr. M. Scott Perry MD, Medical Director of Neurology and Director of the Genetic Epilepsy Clinic at Cook Children’s shares basic information about the disorder.
What are some of the presentations of SCN2A-related disorders? Children with SCN2A can often present with epilepsy which may manifest in several levels of severity. SCN2A was first discovered as a cause of benign familial neonatal infantile seizures (BFNIS), a syndrome presenting in multiple family members with seizure onset as neonates and infants with normal developmental outcome and 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. SCN2A has been implicated as one of the causes of Ohtahara Syndrome, Dravet Syndrome, Migrating Partial Epilepsy of Infancy and West Syndrome amongst others. Finally, SCN2A has been found to be a major cause of intellectual disability, schizophrenia, and autism which may occur in the absence of epilepsy.
What is the cause of SCN2A-related disorders? SCN2A is a gene which encodes a sodium channel found within the initial segments of neurons. This location is important to determining whether a neuron will generate a signal or not, thus a reason mutations can present with neurological symptoms. Most 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. SCN2A may be inherited in an autosomal dominant manner in more benign presentations such as BFNIS.
How are SCN2A mutations diagnosed? Diagnosis is made using genetic testing in patients with appropriate clinical features. MRI is often normal and EEG findings may vary.
Is there a treatment for SCN2A-related disorders? Unfortunately, there is not yet a cure for SCN2A-related disorders. Certain sodium channel drugs (for example, phenytoin, lamotrigine) have demonstrated more favorable responses for seizure control in some patients, while in others sodium channel drugs may aggravate seizures. This may be due to how the mutation impacts the function of the sodium channel (gain of function versus loss of function). Aggressive control of seizures with a clear rescue plan for prolonged seizures is important. Other manifestations such as movement disorders, dysautonomia, and neurobehavioral manifestations can be managed to some degree with medications and therapy.
What other problems might be found in patients with SCN2A disorders? In addition to epilepsy and developmental delays, other manifestations of SCN2A can include movement disorders such as dystonia, abnormal gait, ADHD, autism, dysautonomia (i.e. problems with heart rate, blood pressure, and temperature regulation), and GI problems such as feeding difficulties or reflux.
For more information about SCN2A and SCN2A Awareness Day, visit www.scn2a.org.
Get to know M. Scott Perry, M.D.
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' well-being. Click to learn more.