This template was built with Webflow's free Prospero UI Kit. Learn more
.jpg)
If your child has recently been diagnosed with a change in the SCN2A gene, you are probably swimming in unfamiliar language. Genes, sodium channels, variants, phenotypes. It can feel overwhelming when you are also processing difficult emotions and making decisions about your child's care.
This guide is here to help. Below, we explain what the SCN2A gene does, why the specific type of genetic change matters, what conditions are associated with SCN2A, and what the latest research means for your family. Our goal is simple: give you a clear, honest, and hopeful foundation of knowledge. Understanding the science is one of the most powerful things you can do for your child.
Genes are instruction sets encoded in our DNA. Each gene tells the body how to build a specific protein, a working part the body needs to function. The SCN2A gene sits on chromosome 2 and contains the instructions for building a protein called Nav1.2, a type of voltage-gated sodium channel.
Sodium channels are gateways on the surface of brain cells (neurons). When they open, they allow sodium ions to rush into the cell, creating the electrical signals neurons use to communicate. Think of them as a precisely timed switch for electrical activity in the brain.
Nav1.2 is found primarily on excitatory neurons. In the developing brain, it is concentrated at the axon initial segment, the cell body, and the dendrites. It plays important roles in starting electrical signals, integrating incoming signals from other neurons, and sending signals back through the cell. As the brain matures, another sodium channel (Nav1.6) gradually takes over some of Nav1.2's responsibilities in certain regions. This developmental shift helps explain why the timing and presentation of symptoms can vary depending on when in development the channel's function is most critical.
To learn more about the SCN2A gene and what it means for your family, visit our dedicated overview page.
A genetic variant is any change in the DNA sequence of a gene. Not all variants cause problems. Some are harmless, some have uncertain effects, and some disrupt how the gene works. When a laboratory determines that a specific variant is responsible for causing disease, it is classified as pathogenic or likely pathogenic using standardized guidelines from the American College of Medical Genetics and Genomics (ACMG). The word "mutation" is still widely used in everyday language, but clinicians and researchers increasingly prefer the term "variant" because it avoids implying that every DNA change is harmful.
When the SCN2A gene carries a disease-causing variant, the Nav1.2 sodium channel does not function normally. Electrical signaling in the brain is disrupted. The consequences depend on the nature of the specific change. Not all SCN2A variants cause the channel to malfunction in the same way, and this distinction has direct implications for understanding a child's diagnosis and care.
In most cases, disease-causing SCN2A variants occur de novo. This means the change arises spontaneously for the first time in the child and was not inherited from either parent. De novo variants are especially common in severe presentations such as developmental and epileptic encephalopathy.
In a smaller number of cases, the variant is inherited from a parent, following an autosomal dominant pattern. This is more common in milder, self-limited forms of epilepsy, where a parent may carry the same variant with mild or no symptoms. It is also possible for a parent to carry a variant in only some of their cells, a phenomenon called mosaicism. In these cases, standard blood testing in the parent may come back negative even though the variant can still be passed to a child. A genetic counselor can help clarify which scenario applies to your family and discuss recurrence risk.
One of the most important things caregivers can understand about an SCN2A diagnosis is that not all variants work the same way. Researchers classify SCN2A variants into functional categories, and this distinction matters for understanding your child's condition and guiding their care.
Gain-of-function (GOF) variants cause the Nav1.2 sodium channel to be more active than normal. This increased activity can happen through several different biophysical mechanisms. In some cases the channel opens too easily, in others it fails to close properly, and in others it recovers too quickly between firings. The shared result is greater overall electrical excitability in neurons. This overactivity typically leads to early-onset seizures, often beginning in the first weeks or months of life. Children with GOF variants may be diagnosed with early infantile epilepsy or Developmental and Epileptic Encephalopathy (DEE). Some children experience seizures that are difficult to control, while others have self-limited forms that may resolve in early childhood.
Loss-of-function (LOF) variants reduce Nav1.2 channel activity. One common LOF mechanism is haploinsufficiency, where one copy of the gene is disrupted so severely (by a deletion, truncation, or splice-site change) that the body cannot produce enough working Nav1.2 protein from the remaining copy alone. However, not every LOF variant works through classic haploinsufficiency. Some missense variants produce a channel that still reaches the cell surface but functions at reduced capacity, or that is impaired in specific ways. The functional picture can be complex.
LOF variants are more often associated with autism spectrum disorder (ASD) and developmental differences, with or without seizures. When seizures do occur in LOF cases, they tend to appear later in life rather than in infancy.
Because LOF variants reduce channel activity, medications that further decrease sodium channel function (known as sodium channel blockers) may be less effective or could potentially worsen seizures in some individuals. However, treatment response is not determined perfectly by a broad GOF or LOF label. Medication decisions should always be individualized based on a child's seizure type, age of onset, functional evidence, and specialist evaluation. Families should never change medication based solely on reading about variant classification. This is a conversation to have with your child's neurologist.
Some SCN2A variants do not fit neatly into the GOF or LOF category. These mixed-function variants may show features of both increased and decreased channel activity depending on context, or their functional impact may not yet be fully characterized. Research into these variants is ongoing. Families whose child carries a mixed-function or unclassified variant can discuss the implications with their medical team and genetic counselor.
For a detailed look at the symptoms associated with each variant type, read our SCN2A symptoms guide for families.
SCN2A variants are associated with a range of neurological and developmental conditions. The specific presentation varies widely between individuals, even among those with similar variants. Your child's experience is unique. The sections below describe the most commonly reported presentations, but many children show features of more than one category.
Epilepsy is one of the most common presentations, particularly in children with GOF variants. Seizures may begin in the neonatal period (the first four weeks of life) or during infancy. Some children experience seizures that are difficult to control with medication. Others may have milder seizure types that respond well to treatment. In some cases, particularly with certain self-limited variant types, seizures resolve within the first two years of life.
SCN2A is a high-confidence autism-associated gene with one of the strongest established single-gene associations with autism spectrum disorder (ASD). Children with SCN2A-related ASD may show early signs such as limited eye contact, delayed speech, and differences in social interaction. Many children are deeply engaged with their caregivers in their own way, even when verbal communication is limited.
Many children with SCN2A variants experience some degree of developmental difference, ranging from mild delays to more significant intellectual disability. Areas that may be affected include speech and language, motor skills, memory, and learning. Every child's profile is different, and progress unfolds on its own timeline.
Some individuals with SCN2A variants experience motor challenges, including low muscle tone (hypotonia), difficulty with coordination, dystonia, or episodic ataxia. These findings are less common than seizures or developmental differences but remain an important part of the full clinical picture.
An SCN2A variant is identified through genetic testing. The most common methods include epilepsy gene panel tests, whole exome sequencing (WES), and whole genome sequencing (WGS). Depending on the situation, additional analyses such as deletion/duplication testing or copy-number analysis may also be relevant.
Genetic testing is typically ordered by a pediatric neurologist, geneticist, or genetic counselor after a child presents with unexplained seizures, developmental delay, or autism. Many families receive a diagnosis after months or even years of searching for answers. The SCN2A Foundation advocates strongly for early and accessible genetic testing because a genetic diagnosis can directly shape treatment decisions.
The diagnostic journey can feel long and uncertain. If earlier testing came back inconclusive, it may be worth discussing updated testing options with your medical team. Genetic testing technology has improved significantly, and variants that were previously undetectable may now be identifiable.
Once a variant is identified, a genetic counselor can help interpret the laboratory's findings, including whether the variant is classified as pathogenic, likely pathogenic, or of uncertain significance. This pathogenicity classification is different from functional classification (GOF vs. LOF), which may require additional research such as published electrophysiology studies, computational analysis, or comparison with previously characterized variants. Many missense variants remain functionally uncertain. The Foundation is working to advance SCN2A research and emerging therapies that depend on this kind of precise genetic information.
A diagnosis is the beginning of a new chapter. It comes with a name, a direction, and a community. For many families, receiving an SCN2A diagnosis after months of uncertainty brings a complex mix of grief and relief. The name does not change your child. It changes what is possible for their care.
With a genetic diagnosis in hand, conversations with your child's medical team become more focused. Medication choices, therapy priorities, and long-term planning can all be shaped by the specific variant your child carries. A diagnosis also opens doors to research programs that may not have been available before.
Care for children with SCN2A variants is typically multidisciplinary. A team may include neurologists, developmental pediatricians, speech and occupational therapists, and behavioral health specialists. Each child's care plan looks different because each child's needs are different.
You do not have to figure this out alone. Connect with the SCN2A Foundation community to find support, practical resources, and connection with other families who understand what you are going through.
The pace of SCN2A research has accelerated significantly. Scientists now have a deeper understanding of how different SCN2A variants work and what that means for developing therapies that target the root cause of the disorder. Several programs are actively advancing toward the clinic.
Elsunersen is an investigational antisense oligonucleotide (ASO) being developed by Praxis Precision Medicines. An ASO is a short, synthetic strand of genetic material designed to modulate the activity of a target gene. Elsunersen is designed to selectively decrease SCN2A gene expression, targeting the underlying cause of seizures in children with early-seizure-onset SCN2A-DEE caused by gain-of-function variants. The EMBRAVE clinical trials have enrolled participants aged 2 to 18 with a documented SCN2A variant and seizure onset prior to 3 months of age. Elsunersen is not FDA approved and remains under clinical investigation.
In the Phase 1/2 EMBRAVE Part A trial, Praxis reported results from nine pediatric patients aged 2 to 12 who were randomized 3:1 to receive either elsunersen or a sham procedure every four weeks for 24 weeks. The company reported a 77% sham-adjusted reduction in monthly seizures from baseline (p=0.015, 95% CI 33 to 92). According to Praxis, 71% of elsunersen-treated patients achieved greater than 50% seizure reduction, and 57% experienced at least one 28-day seizure-free period. Treatment benefits were sustained for up to one year in an ongoing open-label extension. These results were announced by the sponsor and have not yet been published in a peer-reviewed journal.
In June 2026, the FDA granted elsunersen Breakthrough Therapy Designation. This designation is intended to expedite the development and review of therapies for serious conditions. It is not an approval and does not establish that the treatment is safe or effective. The pivotal EMBRAVE3 registrational study is currently enrolling under a single-arm, baseline-controlled design.
For children whose loss-of-function variant causes haploinsufficiency (where one copy of the gene is disrupted and the remaining copy cannot produce enough Nav1.2 protein), researchers at the University of California, San Francisco (UCSF) published preclinical results in Nature in 2025 exploring a technology called CRISPRa (CRISPR activation). Unlike conventional gene editing, CRISPRa does not cut or rewrite DNA. Instead, it increases how much protein the existing healthy copy of the gene produces.
The study, from the laboratories of Dr. Kevin Bender and Dr. Nadav Ahituv at UCSF, tested this approach in mouse models and in human neurons grown in a laboratory (not in patients). In mice, the treatment improved brain-cell function and made the animals less prone to seizures. In human neurons grown in a laboratory, restoring SCN2A protein levels allowed the cells to grow normal-length connections capable of linking with other nerve cells. These are promising preclinical findings, but this approach has not yet been tested in people. Regel Therapeutics has licensed UCSF's CRISPRa technology to develop treatments for SCN2A haploinsufficiency. As the researchers noted, future work will need to confirm the safety of this approach in humans.
SCN2A is one of the most broadly researched rare disease genes, with active clinical networks and a growing base of natural history data. Several publicly available databases and registries allow families, researchers, and clinicians to access and contribute to the global knowledge base around SCN2A. Below are some of the most important resources.
Simons Searchlight is a research program that collects genetic data and medical histories from individuals with SCN2A and other neurodevelopmental gene variants. Families who enroll contribute to a growing database that researchers worldwide use to study how SCN2A-related disorders present and progress over time. Simons Searchlight also provides gene guides written for families and connects participants with new research opportunities.
PubMed is a free database maintained by the National Library of Medicine where families and researchers can find published medical research about SCN2A. Searching "SCN2A" on PubMed returns citations for scientific articles on the gene, including clinical studies, case reports, and laboratory research, often with links to the full text.
ClinVar is a public archive hosted by the National Center for Biotechnology Information (NCBI) that collects reports on the relationship between specific genetic variants and human health conditions. For SCN2A, ClinVar contains records showing how individual variants have been classified (pathogenic, likely pathogenic, uncertain significance, likely benign, or benign) by clinical laboratories. This resource helps clinicians and genetic counselors interpret a child's specific variant in the context of what is already known.
The Jackson Laboratory (JAX) develops and distributes genetically defined mouse models used in biomedical research. JAX maintains SCN2A mouse strains that allow researchers to study how specific SCN2A variants affect brain function, behavior, and seizure susceptibility in a controlled setting. These animal models are a critical step in testing potential therapies before they can move into human clinical trials.
The Human Protein Atlas is a Swedish-based research program that maps where human genes are expressed across cells, tissues, and organs. It presents two complementary types of data: protein-level data (generated through antibody-based imaging of tissue samples) and RNA-level data (generated through RNA sequencing, which measures gene transcript activity). For SCN2A, the Atlas shows that expression is concentrated in the brain and central nervous system. Comparing the RNA and protein data helps researchers understand which brain regions and cell types are most affected by SCN2A variants and informs the design of targeted therapies.
Families can also contribute directly to research by enrolling in the Dragonfly Study, a longitudinal natural history registry for individuals with SCN2A-related disorders of all variant types. The Dragonfly Study is sponsored by FamilieSCN2A Foundation and hosted through NORD's IAMRARE platform. It collects information on diagnosis, symptoms, treatment, and outcomes over time. Natural history data like this can support clinical trial design, regulatory review, endpoint selection, and the interpretation of treatment outcomes. Every family that participates is helping build the evidence base that future therapies will depend on.
Every family navigating an SCN2A diagnosis deserves answers, access to emerging research, and real hope for the future. There are three powerful ways to be part of the work that moves us forward.
Join the SCN2A World Map to connect with the global SCN2A community and help us understand the full scope of SCN2A-related disorders worldwide.
Sign up for the contact registry to ensure your family is part of the network shaping what comes next, including research opportunities and clinical trial updates.
And if you are able, please consider making a donation to help fund the research and resources that bring us all closer to answers.
Medical Disclaimer: This content is provided for educational and informational purposes only and does not constitute medical advice. The information on this page is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the guidance of a qualified healthcare provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
3. Children's Hospital of Philadelphia — SCN2A-Related Disorders
4. Simons Searchlight — SCN2A Gene Guide
9. Praxis Precision Medicines — EMBRAVE Part A Topline Results, April 2026
10. Praxis Precision Medicines — Elsunersen Breakthrough Therapy Designation, June 2026
11. Tamura S. et al. (2025) — CRISPR Activation Restores SCN2A Expression. Nature
12. The Dragonfly Study — SCN2A Natural History Registry (IAMRARE)
13. ClinVar — SCN2A Variant Archive
15. The Human Protein Atlas — SCN2A
16. The Jackson Laboratory — SCN2A Mouse Models
17. ClinicalTrials.gov — EMBRAVE Trial of PRAX-222 (NCT05737784)
Share
If your child has recently been diagnosed with a change in the SCN2A gene, you are probably swimming in unfamiliar language. Genes, sodium channels, variants, phenotypes. It can feel overwhelming when you are also processing difficult emotions and making decisions about your child's care.
This guide is here to help. Below, we explain what the SCN2A gene does, why the specific type of genetic change matters, what conditions are associated with SCN2A, and what the latest research means for your family. Our goal is simple: give you a clear, honest, and hopeful foundation of knowledge. Understanding the science is one of the most powerful things you can do for your child.
Genes are instruction sets encoded in our DNA. Each gene tells the body how to build a specific protein, a working part the body needs to function. The SCN2A gene sits on chromosome 2 and contains the instructions for building a protein called Nav1.2, a type of voltage-gated sodium channel.
Sodium channels are gateways on the surface of brain cells (neurons). When they open, they allow sodium ions to rush into the cell, creating the electrical signals neurons use to communicate. Think of them as a precisely timed switch for electrical activity in the brain.
Nav1.2 is found primarily on excitatory neurons. In the developing brain, it is concentrated at the axon initial segment, the cell body, and the dendrites. It plays important roles in starting electrical signals, integrating incoming signals from other neurons, and sending signals back through the cell. As the brain matures, another sodium channel (Nav1.6) gradually takes over some of Nav1.2's responsibilities in certain regions. This developmental shift helps explain why the timing and presentation of symptoms can vary depending on when in development the channel's function is most critical.
To learn more about the SCN2A gene and what it means for your family, visit our dedicated overview page.
A genetic variant is any change in the DNA sequence of a gene. Not all variants cause problems. Some are harmless, some have uncertain effects, and some disrupt how the gene works. When a laboratory determines that a specific variant is responsible for causing disease, it is classified as pathogenic or likely pathogenic using standardized guidelines from the American College of Medical Genetics and Genomics (ACMG). The word "mutation" is still widely used in everyday language, but clinicians and researchers increasingly prefer the term "variant" because it avoids implying that every DNA change is harmful.
When the SCN2A gene carries a disease-causing variant, the Nav1.2 sodium channel does not function normally. Electrical signaling in the brain is disrupted. The consequences depend on the nature of the specific change. Not all SCN2A variants cause the channel to malfunction in the same way, and this distinction has direct implications for understanding a child's diagnosis and care.
In most cases, disease-causing SCN2A variants occur de novo. This means the change arises spontaneously for the first time in the child and was not inherited from either parent. De novo variants are especially common in severe presentations such as developmental and epileptic encephalopathy.
In a smaller number of cases, the variant is inherited from a parent, following an autosomal dominant pattern. This is more common in milder, self-limited forms of epilepsy, where a parent may carry the same variant with mild or no symptoms. It is also possible for a parent to carry a variant in only some of their cells, a phenomenon called mosaicism. In these cases, standard blood testing in the parent may come back negative even though the variant can still be passed to a child. A genetic counselor can help clarify which scenario applies to your family and discuss recurrence risk.
One of the most important things caregivers can understand about an SCN2A diagnosis is that not all variants work the same way. Researchers classify SCN2A variants into functional categories, and this distinction matters for understanding your child's condition and guiding their care.
Gain-of-function (GOF) variants cause the Nav1.2 sodium channel to be more active than normal. This increased activity can happen through several different biophysical mechanisms. In some cases the channel opens too easily, in others it fails to close properly, and in others it recovers too quickly between firings. The shared result is greater overall electrical excitability in neurons. This overactivity typically leads to early-onset seizures, often beginning in the first weeks or months of life. Children with GOF variants may be diagnosed with early infantile epilepsy or Developmental and Epileptic Encephalopathy (DEE). Some children experience seizures that are difficult to control, while others have self-limited forms that may resolve in early childhood.
Loss-of-function (LOF) variants reduce Nav1.2 channel activity. One common LOF mechanism is haploinsufficiency, where one copy of the gene is disrupted so severely (by a deletion, truncation, or splice-site change) that the body cannot produce enough working Nav1.2 protein from the remaining copy alone. However, not every LOF variant works through classic haploinsufficiency. Some missense variants produce a channel that still reaches the cell surface but functions at reduced capacity, or that is impaired in specific ways. The functional picture can be complex.
LOF variants are more often associated with autism spectrum disorder (ASD) and developmental differences, with or without seizures. When seizures do occur in LOF cases, they tend to appear later in life rather than in infancy.
Because LOF variants reduce channel activity, medications that further decrease sodium channel function (known as sodium channel blockers) may be less effective or could potentially worsen seizures in some individuals. However, treatment response is not determined perfectly by a broad GOF or LOF label. Medication decisions should always be individualized based on a child's seizure type, age of onset, functional evidence, and specialist evaluation. Families should never change medication based solely on reading about variant classification. This is a conversation to have with your child's neurologist.
Some SCN2A variants do not fit neatly into the GOF or LOF category. These mixed-function variants may show features of both increased and decreased channel activity depending on context, or their functional impact may not yet be fully characterized. Research into these variants is ongoing. Families whose child carries a mixed-function or unclassified variant can discuss the implications with their medical team and genetic counselor.
For a detailed look at the symptoms associated with each variant type, read our SCN2A symptoms guide for families.
SCN2A variants are associated with a range of neurological and developmental conditions. The specific presentation varies widely between individuals, even among those with similar variants. Your child's experience is unique. The sections below describe the most commonly reported presentations, but many children show features of more than one category.
Epilepsy is one of the most common presentations, particularly in children with GOF variants. Seizures may begin in the neonatal period (the first four weeks of life) or during infancy. Some children experience seizures that are difficult to control with medication. Others may have milder seizure types that respond well to treatment. In some cases, particularly with certain self-limited variant types, seizures resolve within the first two years of life.
SCN2A is a high-confidence autism-associated gene with one of the strongest established single-gene associations with autism spectrum disorder (ASD). Children with SCN2A-related ASD may show early signs such as limited eye contact, delayed speech, and differences in social interaction. Many children are deeply engaged with their caregivers in their own way, even when verbal communication is limited.
Many children with SCN2A variants experience some degree of developmental difference, ranging from mild delays to more significant intellectual disability. Areas that may be affected include speech and language, motor skills, memory, and learning. Every child's profile is different, and progress unfolds on its own timeline.
Some individuals with SCN2A variants experience motor challenges, including low muscle tone (hypotonia), difficulty with coordination, dystonia, or episodic ataxia. These findings are less common than seizures or developmental differences but remain an important part of the full clinical picture.
An SCN2A variant is identified through genetic testing. The most common methods include epilepsy gene panel tests, whole exome sequencing (WES), and whole genome sequencing (WGS). Depending on the situation, additional analyses such as deletion/duplication testing or copy-number analysis may also be relevant.
Genetic testing is typically ordered by a pediatric neurologist, geneticist, or genetic counselor after a child presents with unexplained seizures, developmental delay, or autism. Many families receive a diagnosis after months or even years of searching for answers. The SCN2A Foundation advocates strongly for early and accessible genetic testing because a genetic diagnosis can directly shape treatment decisions.
The diagnostic journey can feel long and uncertain. If earlier testing came back inconclusive, it may be worth discussing updated testing options with your medical team. Genetic testing technology has improved significantly, and variants that were previously undetectable may now be identifiable.
Once a variant is identified, a genetic counselor can help interpret the laboratory's findings, including whether the variant is classified as pathogenic, likely pathogenic, or of uncertain significance. This pathogenicity classification is different from functional classification (GOF vs. LOF), which may require additional research such as published electrophysiology studies, computational analysis, or comparison with previously characterized variants. Many missense variants remain functionally uncertain. The Foundation is working to advance SCN2A research and emerging therapies that depend on this kind of precise genetic information.
A diagnosis is the beginning of a new chapter. It comes with a name, a direction, and a community. For many families, receiving an SCN2A diagnosis after months of uncertainty brings a complex mix of grief and relief. The name does not change your child. It changes what is possible for their care.
With a genetic diagnosis in hand, conversations with your child's medical team become more focused. Medication choices, therapy priorities, and long-term planning can all be shaped by the specific variant your child carries. A diagnosis also opens doors to research programs that may not have been available before.
Care for children with SCN2A variants is typically multidisciplinary. A team may include neurologists, developmental pediatricians, speech and occupational therapists, and behavioral health specialists. Each child's care plan looks different because each child's needs are different.
You do not have to figure this out alone. Connect with the SCN2A Foundation community to find support, practical resources, and connection with other families who understand what you are going through.
The pace of SCN2A research has accelerated significantly. Scientists now have a deeper understanding of how different SCN2A variants work and what that means for developing therapies that target the root cause of the disorder. Several programs are actively advancing toward the clinic.
Elsunersen is an investigational antisense oligonucleotide (ASO) being developed by Praxis Precision Medicines. An ASO is a short, synthetic strand of genetic material designed to modulate the activity of a target gene. Elsunersen is designed to selectively decrease SCN2A gene expression, targeting the underlying cause of seizures in children with early-seizure-onset SCN2A-DEE caused by gain-of-function variants. The EMBRAVE clinical trials have enrolled participants aged 2 to 18 with a documented SCN2A variant and seizure onset prior to 3 months of age. Elsunersen is not FDA approved and remains under clinical investigation.
In the Phase 1/2 EMBRAVE Part A trial, Praxis reported results from nine pediatric patients aged 2 to 12 who were randomized 3:1 to receive either elsunersen or a sham procedure every four weeks for 24 weeks. The company reported a 77% sham-adjusted reduction in monthly seizures from baseline (p=0.015, 95% CI 33 to 92). According to Praxis, 71% of elsunersen-treated patients achieved greater than 50% seizure reduction, and 57% experienced at least one 28-day seizure-free period. Treatment benefits were sustained for up to one year in an ongoing open-label extension. These results were announced by the sponsor and have not yet been published in a peer-reviewed journal.
In June 2026, the FDA granted elsunersen Breakthrough Therapy Designation. This designation is intended to expedite the development and review of therapies for serious conditions. It is not an approval and does not establish that the treatment is safe or effective. The pivotal EMBRAVE3 registrational study is currently enrolling under a single-arm, baseline-controlled design.
For children whose loss-of-function variant causes haploinsufficiency (where one copy of the gene is disrupted and the remaining copy cannot produce enough Nav1.2 protein), researchers at the University of California, San Francisco (UCSF) published preclinical results in Nature in 2025 exploring a technology called CRISPRa (CRISPR activation). Unlike conventional gene editing, CRISPRa does not cut or rewrite DNA. Instead, it increases how much protein the existing healthy copy of the gene produces.
The study, from the laboratories of Dr. Kevin Bender and Dr. Nadav Ahituv at UCSF, tested this approach in mouse models and in human neurons grown in a laboratory (not in patients). In mice, the treatment improved brain-cell function and made the animals less prone to seizures. In human neurons grown in a laboratory, restoring SCN2A protein levels allowed the cells to grow normal-length connections capable of linking with other nerve cells. These are promising preclinical findings, but this approach has not yet been tested in people. Regel Therapeutics has licensed UCSF's CRISPRa technology to develop treatments for SCN2A haploinsufficiency. As the researchers noted, future work will need to confirm the safety of this approach in humans.
SCN2A is one of the most broadly researched rare disease genes, with active clinical networks and a growing base of natural history data. Several publicly available databases and registries allow families, researchers, and clinicians to access and contribute to the global knowledge base around SCN2A. Below are some of the most important resources.
Simons Searchlight is a research program that collects genetic data and medical histories from individuals with SCN2A and other neurodevelopmental gene variants. Families who enroll contribute to a growing database that researchers worldwide use to study how SCN2A-related disorders present and progress over time. Simons Searchlight also provides gene guides written for families and connects participants with new research opportunities.
PubMed is a free database maintained by the National Library of Medicine where families and researchers can find published medical research about SCN2A. Searching "SCN2A" on PubMed returns citations for scientific articles on the gene, including clinical studies, case reports, and laboratory research, often with links to the full text.
ClinVar is a public archive hosted by the National Center for Biotechnology Information (NCBI) that collects reports on the relationship between specific genetic variants and human health conditions. For SCN2A, ClinVar contains records showing how individual variants have been classified (pathogenic, likely pathogenic, uncertain significance, likely benign, or benign) by clinical laboratories. This resource helps clinicians and genetic counselors interpret a child's specific variant in the context of what is already known.
The Jackson Laboratory (JAX) develops and distributes genetically defined mouse models used in biomedical research. JAX maintains SCN2A mouse strains that allow researchers to study how specific SCN2A variants affect brain function, behavior, and seizure susceptibility in a controlled setting. These animal models are a critical step in testing potential therapies before they can move into human clinical trials.
The Human Protein Atlas is a Swedish-based research program that maps where human genes are expressed across cells, tissues, and organs. It presents two complementary types of data: protein-level data (generated through antibody-based imaging of tissue samples) and RNA-level data (generated through RNA sequencing, which measures gene transcript activity). For SCN2A, the Atlas shows that expression is concentrated in the brain and central nervous system. Comparing the RNA and protein data helps researchers understand which brain regions and cell types are most affected by SCN2A variants and informs the design of targeted therapies.
Families can also contribute directly to research by enrolling in the Dragonfly Study, a longitudinal natural history registry for individuals with SCN2A-related disorders of all variant types. The Dragonfly Study is sponsored by FamilieSCN2A Foundation and hosted through NORD's IAMRARE platform. It collects information on diagnosis, symptoms, treatment, and outcomes over time. Natural history data like this can support clinical trial design, regulatory review, endpoint selection, and the interpretation of treatment outcomes. Every family that participates is helping build the evidence base that future therapies will depend on.
Every family navigating an SCN2A diagnosis deserves answers, access to emerging research, and real hope for the future. There are three powerful ways to be part of the work that moves us forward.
Join the SCN2A World Map to connect with the global SCN2A community and help us understand the full scope of SCN2A-related disorders worldwide.
Sign up for the contact registry to ensure your family is part of the network shaping what comes next, including research opportunities and clinical trial updates.
And if you are able, please consider making a donation to help fund the research and resources that bring us all closer to answers.
Medical Disclaimer: This content is provided for educational and informational purposes only and does not constitute medical advice. The information on this page is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the guidance of a qualified healthcare provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
3. Children's Hospital of Philadelphia — SCN2A-Related Disorders
4. Simons Searchlight — SCN2A Gene Guide
9. Praxis Precision Medicines — EMBRAVE Part A Topline Results, April 2026
10. Praxis Precision Medicines — Elsunersen Breakthrough Therapy Designation, June 2026
11. Tamura S. et al. (2025) — CRISPR Activation Restores SCN2A Expression. Nature
12. The Dragonfly Study — SCN2A Natural History Registry (IAMRARE)
13. ClinVar — SCN2A Variant Archive
15. The Human Protein Atlas — SCN2A
16. The Jackson Laboratory — SCN2A Mouse Models
17. ClinicalTrials.gov — EMBRAVE Trial of PRAX-222 (NCT05737784)
Vlad Magdalin
Accelerating research and treatment for SCN2A-related disorders.
Get the latest SCN2A research and community news.