SCN2A-related disorders

SCN2A-related disorders are a group of rare neurodevelopmental disorders caused by pathogenic variants in the SCN2A gene, which encodes a subunit of the voltage-gated sodium channel NaV1.2.^[1] Mutations in the SCN2A gene can cause a broad spectrum of disorders collectively referred to as SCN2A-related disorders. These include cases of autism, self-limited epilepsy, early infantile developmental and epileptic encephalopathy, later onset developmental and epileptic encephalopathy, infantile spasms, SCN2A-related disorders without epilepsy, episodic ataxia, and further movement disorders.

Clinical significance

Main article: SCN2A

Mutations in the SCN2A gene can cause a broad spectrum of disorders collectively referred to as SCN2A-related disorders. These include cases of autism^[2], self-limited epilepsy, early infantile developmental and epileptic encephalopathy, later onset developmental and epileptic encephalopathy, infantile spasms, SCN2A-related disorders without epilepsy, episodic ataxia, and further movement disorders.^[1] Two major groups of SCN2A mutations can be distinguished based on their functional consequences and response to seizure medication: gain of function mutations, typically associated with seizure onset within the first three months of life, and loss of function mutations, in which seizures begin after the first three months or may never occur. The former group tends to benefit from treatment with sodium channel blockers, whereas in the latter, such treatment is often ineffective or may even exacerbate seizures.^[3] Notably, SCN2A is known to be the most prominent genetic risk factor for autism-spectrum-disorders.^[2]

SCN2A gene mutations have also been identified in bitemporal glucose hypometabolism^[4], and bipolar disorder.^[5]

February 24th - International SCN2A Awareness Day

Main article: International SCN2A Awareness Day

International SCN2A Awareness Day is globally recognized as February 24 each year. The goal is to raise awareness of disorders caused by pathological variants in the SCN2A gene, including epilepsy, autism, intellectual disability, and self-limited familial infantile epilepsy (SelFIE). Advocacy goals for SCN2A Awareness Day include improving care, funding research and community support efforts, and promoting early genetic testing and counseling.

ICD-10-CM Code

Effective October 1, 2025, the ICD-10-CM code for SCN2A-related neurodevelopmental disorder is QA0.0101.^[6]

External Links

SCN2A Patient Advocacy Organizations (PAOs / PAGs)

• FamilieSCN2A Foundation (United States / Global)
• SCN2A SCN2A Australia
• SCN2A Brasil
• SCN2A Georgia
• SCN2A Europe
• SCN2A Foundation (United States)
• SCN2A Germany e. V.
• SCN2A Italia
• SCN2A UK
• SCN2A Ukraine

Further reading

Review Articles

• SCN2A-Related Disorders – Elements in Genetics in Epilepsy^[1]

Genotype/Phenotype

• Expanded clinical phenotype spectrum correlates with variant function in SCN2A-related disorders^[7]
• Assessing communication impairments in a rare neurodevelopmental disorder: The SCN2A Clinical Trials Readiness Study^[8]
• Decoding SCN2A Variants: Bridging Genetics and Phenotypes in Autism Spectrum Disorder^[9]
• Expanded clinical phenotype spectrum correlates with variant function in SCN2A -related disorders ^[10]
• Gene variant effects across sodium channelopathies predict function and guide precision therapy^[11]
• Computational analysis of 10,860 phenotypic annotations in individuals with SCN2A-related disorders^[12]
• Large-scale exome sequencing study implicates both developmental and functional changes in the neurobiology of autism^[13]
• Phenotypic spectrum and genetics of SCN2A‐related disorders, treatment options, and outcomes in epilepsy and beyond^[14]
• Found in translation: Autism genetics and the quest for its Rosetta Stone^[15]
• Progress in understanding and treating SCN2A-mediated disorders^[16]
• Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders^[17]
• SCN2A – a 2016 update^[18]
• Story of a genetic shape-shifter: SCN2A in benign seizures, autism and epileptic encephalopathy^[19]

Treatment (Current and Emerging)

• CRISPR activation for SCN2A-related neurodevelopmental disorders^[20]
• Antisense oligonucleotide treatment in a preterm infant with early-onset SCN2A developmental and epileptic encephalopathy^[21]

Research Readiness, Clinical Outcome Assessments, and Clinical Trial Design

• A Patient Organization Perspective: charting the course to a cure for SCN2A-related disorders ^[22]
• The feasibility of personalized endpoints in assessing treatment outcomes for rare diseases: a pilot study of goal attainment scaling in SCN2A-associated Developmental Epileptic Encephalopathy^[23]
• Vineland-3 growth scale values: psychometric properties for clinical trial readiness in SCN2A^[24]
• What does better look like in individuals with severe neurodevelopmental impairments? A qualitative descriptive study on SCN2A-related developmental and epileptic encephalopathy^[25]
• Novel approaches to measuring cognition in individuals with severe to profound functional impairment: A pilot study in SCN2A-related disorder^[26]
• Caregiver assessment of quality of life in individuals with genetic developmental and epileptic encephalopathies^[27]
• SCN2A-Developmental and Epileptic Encephalopathies: Challenges to trial-readiness for non-seizure outcomes^[28]