SCN2A Learning Portal
Continuing Medical Education (CME) and other learning opportunities for professionals
Introduction to SCN2A-Related Disorders
Clinicians can learn the essentials of SCN2A-related disorders and receive CME credit in just 15 minutes.
The video entitled "Introduction to SCN2A-Related Disorders for Clinicians and Professionals" is part 1 of the 2026 SCN2A-Related Disorders Continuing Medical Education Series. Click on the poster below to watch the video, or scroll down to see individual chapters and narration text.
This activity has been approved for AMA PRA Category 1 Credit™.
See below for more details and to take the post-video survey.
2026 Science Talk Series
February 20, 2026
Jun Hee Kim, PhD-
Kresge Hearing Research Institute, Department of Otolaryngology–Head and Neck Surgery,
University of Michigan, Ann Arbor
Topic: SCN2A-linked Oligodendrocyte Dysfunction and Autism Spectrum Disorder
Nick Page,
Neuroscience PhD Candidate,
University of California San Francisco
Topic: Discovery and Characterization of the SCN2A Enhancer for Cis-Regulation Therapies
The 2026 SCN2A Science Talk Series has been approved for AMA PRA Category 1 Credit™.
Continuing Medical Education (CME)
CME Statement: This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of the Minnesota Medical Association and FamilieSCN2A Foundation. The Minnesota Medical Association (MMA) is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.
This activity has been approved for AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Disclosure to learners: None of the planners for this educational activity have relevant financial relationship(s) to disclose with ineligible companies whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.
Clinician Resources
Please visit our Clinician Information page for comprehensive resources for professionals, including comprehensive review articles, clinical care resources, and emergency protocols.
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Credits and Acknowledgements
CME Planning Team:
Caitlin Anderson, PhD - Harvard University Medical School; FamilieSCN2A TASCO
Eloise Austin, MD - Columbia University; FamilieSCN2A TASCO and MSAB
Melody Kisor, MS, BCPA - Director of Advocacy, FamilieSCN2A Foundation
Lizz Lyon, MS, MSCR, CGC - Genetic Counseling Volunteer, FamilieSCN2A Foundation
Leah Schust Myers - Executive Director, FamilieSCN2A Foundation
Mery Oman, MSN, FNP-C - Vice Chair of Board of Trustees, FamilieSCN2A Foundation
Morgan Weberg, BS - Research Coordinator, FamilieSCN2A
Foundation
Expert Review:
Vanessa Bender, PhD - UCSF; Scientific Consultant to FamilieSCN2A TASCO
Jenny Burke, BA - Chair of Board of Trustees, FamilieSCN2A Foundation
Jeffrey Cottrell, PhD - FamilieSCN2A Interim Chief Scientific Officer
Amanda Gale, BA - Director of Programs and Operations, FamilieSCN2A Foundation
Alfred L. George, Jr., M.D. - Northwestern University; FamilieSCN2A Foundation MSAB
Olivia Kim-McManus, M.D. - UCSD
Emile Moura Coelho da Silva, MS, CGC - UTHealth Houston
Christina SanInocencio, PhD, CPH CNP - TASCO; Fairfield University
Elliott Wack, BS, --Graduate Student at University of Pennsylvania; FamilieSCN2A Student Intern
Illustration Team: Kinshasa Anglin and Grace Hanson – Ink Factory Studios
Narration: Caitlin Anderson, PhD and Alfred George, Jr., MD
Design & Style: Kayla Aughe, Amanda Gale, Klaudia Pszczolińska, and Angie Weaver
Music: Licensed from Adobe Stock; selected by Amanda Gale
Quick Video Chapters
Don't have time to watch the whole video? Check out the narration text and view mini clips for each topic below.
Section 1 - SCN2A-Related Disorders
SCN2A-related disorders are a group of neurodevelopmental conditions caused by pathogenic variants in the gene SCN2A that alter neuronal function. SCN2A plays a particularly important role during early brain development, when neuronal networks are being established and refined. Pathogenic variants in SCN2A have been identified as a leading cause of autism spectrum disorder, or ASD, intellectual disability, or ID, and epilepsy.
Section 2 - SCN2A Gene
The SCN2A gene resides on the long arm of chromosome 2 at position 24.3, and encodes the ion conducting subunit of the brain sodium channel designated as NaV1.2. These sodium channels open briefly, allowing sodium ions to flow into neurons of the central nervous system, causing those neurons to fire and send electrical signals to other parts of the body. In other words, they generate action potentials important for nerve impulses that are critical for a properly functioning nervous system.
Section 3 - Genotype / Phenotype
Importantly, SCN2A-related disorders exhibit a strong genotype-phenotype correlation, and can be caused by gain-of-function, loss-of-function, or complex and mixed function variants that have different clinical presentations.
Section 4 - Gain of Function
Roughly 20% of pathogenic SCN2A variants exhibit gain-of-function effects. In these cases, the NaV1.2 channel is altered, often by a missense variant, such that the channel opens more readily, inactivates less completely, or allows a persistent “leak” of sodium current. The net result is increased neuronal excitability that causes developmental epileptic encephalopathy, or DEE, characterized by neonatal or early infantile onset seizures that can vary in type and severity. Mortality is high in this group, most commonly due to Sudden Unexpected Death in Epilepsy (SUDEP), respiratory illnesses, status epilepticus, severe infection, and autonomic nervous system dysfunction.
Section 5 - SeLFNIE
That said, a subset of individuals with gain-of-function SCN2A variants have only modest alterations in sodium channel behavior and may present with an epilepsy phenotype known as Self-Limited Familial Neonatal-Infantile Epilepsy (SeLFNIE). In these cases, seizures typically begin in the neonatal or early infantile period but often improve or remit within the first few years of life, with generally better developmental outcomes than seen in DEE.
Section 6 - Loss of Function
On the other hand, close to 80% of pathogenic variants in SCN2A are loss-of-function variants, meaning channel activity is reduced or absent. Truncating variants, including nonsense, frameshift, and many splice variants, typically fall into this category because they result in an incomplete protein that gets degraded or is non-functional. Certain missense variants can also cause loss of function. In these cases, specific circuits may be under‑active or fail to support normal information processing. Patients with loss-of-function variants typically present with ASD and ID which is characterized by global developmental delay, though about a third of these children also develop childhood-onset seizures that are largely refractory to treatment. The difference in age at which epilepsy presents in children with gain-of-function versus loss-of-function variants is a general trend, but there are exceptions.
Section 7 - Developmental Excitability
You can think of SCN2A as a “developmental excitability” gene: push excitability up too much early on, you get severe epilepsy early in life; push it down or knock it out in certain circuits, you get more of a neurodevelopmental ASD/ID picture, with or without seizures.
Section 8 - Mixed Function
In addition to gain- and loss-of-function variants, some variants are difficult to categorize because they exhibit features of both gain and loss-of-function variants. These are known as mixed-function variants and are associated with a range of phenotypes, including both epilepsy and ASD.
Section 9 - Comorbidities
Comorbidities are common in SCN2A-related disorders and involve all body systems. Be vigilant in diagnosing and treating cortical visual impairment; sleep disorders; autonomic dysfunction; movement disorders like chorea, ataxia, and dystonia; urology issues like infections & urinary retention; spasticity, hypotonia; gastrointestinal dysfunction (especially reflux & constipation); neuropathic pain; speech and language deficit; pulmonary issues and chronic lung disease; scoliosis, osteoporosis, and other orthopedic issues.
Section 10 - Diagnostic Red Flags
So when should you suspect SCN2A? From a diagnostic standpoint, there are a few scenarios where SCN2A should be high on your list.One is very early‑onset epilepsy without a clear structural or metabolic cause, particularly focal or tonic seizures in a neonate or young infant. Another is epilepsy with developmental impairment that does not fit a classic electroclinical syndrome, especially when MRI is unrevealing or shows nonspecific findings.On the neurodevelopmental side, SCN2A should be considered in children with ASD and moderate to severe intellectual disability, especially when accompanied by hypotonia, abnormal movements, or a history of seizures or abnormal EEG.
Section 11 - Genetic Testing
In current practice, most diagnoses are made by genetic testing either with targeted epilepsy or neurodevelopmental gene panels, or broader exome or genome sequencing, often in a parent-child trio including both parents. Pathogenic SCN2A variants are most often heterozygous, meaning only one copy of the gene has the variant. Most SCN2A variants also arise de novo, meaning they were not inherited. Once a variant is identified, interpretation follows standard ACMG criteria but benefits from SCN2A‑specific nuance.
Section 12 - Functional Consequence
The clinician should ask: what is the likely functional consequence? Are there published functional data, case series, or at least strong computational predictions that can inform whether the effect is likely gain or loss of function? It’s also important to note that not all variants identified in SCN2A are pathogenic, as many are benign with no discernible effect on protein function. These mechanistic inferences are increasingly important because they shape therapeutic decisions, especially around sodium channel blockers for the treatment of seizures.
Section 13 - Sodium Channel Blockers
In a child whose phenotype and genotype are most consistent with gain‑of‑function, sodium channel blockers may be particularly effective as these agents can counteract hyperexcitability driven by overactive sodium channels.In contrast, in presumed loss‑of‑function or mixed function scenarios associated primarily with ASD and ID phenotypes, sodium channel blockers could exacerbate negative symptoms by further reducing excitability in already compromised networks. In these patients, sodium channel blockers are generally avoided, as the consequences can be severe and potentially lead to irreversible harm.
Sections 14 & 15 - Emerging Treatments and Variant Interpretation
Section 14 & 15 - Emerging TreatmentsUnderstanding the genetic basis of a patient’s SCN2A disorder is also critical for assessing whether they could be eligible for emerging therapies such as gene therapy or antisense oligonucleotide drugs.Because treatment decisions increasingly hinge on gain versus loss of function, collaboration between neurology, clinical genetics, and sometimes research labs is important. And when you’re unsure, it’s crucial to be transparent with families about that uncertainty. If you need assistance interpreting variants, The FamilieSCN2A Foundation can connect you with an international clinical and research network of experts that can help interpret variants.
Section 16 - Comprehensive Care
Equally important is recognizing that optimal management of SCN2A‑related disorders goes far beyond seizures. Early and sustained developmental and behavioral interventions are central to care regardless of seizure burden. These include physical, occupational, and speech therapies, augmentative communication, and autism‑specific supports. Many families will also need help with sleep, feeding, GI issues, and behavior, meaning that partnering early with developmental pediatrics, psychology, and social work is essential. Lifespan coordinated care is ideal, as many adult providers are unfamiliar with SCN2A-related disorders, but in the absence of that, a strong transition plan from pediatric to adult care should begin early and involve coordinated care, especially when transferring facilities.
Section 17 - ICD-10-CM
When documenting SCN2A-related disorders and comorbid conditions in the medical record, it’s important for clinicians to be aware of and use the proper ICD-10 codes. Effective October 1, 2025, the ICD-10-CM code for SCN2A-Related Neurodevelopmental Disorders is QA0.0101. Importantly, this is not meant to replace other condition codes; rather, it should be used in addition to other codes to document the clinical presentation, such as epilepsy and ASD.
Section 18 - Partner with Families
Clinicians should always partner directly with caregivers to make informed care decisions, ensuring the highest quality of life for the affected individual and their families. Consultation with child life specialists and palliative care teams can help provide comfort and support, and in some cases, hospice and end-of-life planning may be indicated.
Section 19 - Advocacy Support
Caregivers should also be referred to the The FamilieSCN2A Foundation, a patient advocacy group that can help connect families with the emotional, educational, and financial resources they need, including home and school supports. The FamilieSCN2A Foundation also provides the opportunity to build community with other affected families, participate in valuable research such as natural history studies, and stay abreast of the latest developments in the field. It cannot be overstated what a profound and tangible difference advocacy support can make in the everyday lives of those living with SCN2A-related disorders.
Section 20 - Key Clinical Messages
For practicing clinicians, the key clinical messages are to use genetic testing early; interpret variants with an eye toward determining gain or loss of function; and let that mechanistic understanding alongside the phenotypic presentation inform your treatment plan. By learning more about SCN2A related disorders, you can help the right patients receive the right treatment at the right time.