Coming soon SCN2A-Related Disorders
Expected online publication date:
01 July 2024
- Alfred L. George, Jr.
- Affiliation:
Northwestern University Feinberg School of Medicine
- Megan Abbott
- Affiliation:
University of Colorado School of Medicine
- Kevin J. Bender
- Affiliation:
University of California, San Francisco
- Andreas Brunklaus
- Affiliation:
Royal Hospital for Children and University of Glasgow
- Scott Demarest
- Affiliation:
University of Colorado School of Medicine
- Shawn Egan
- Affiliation:
FamilieSCN2A Foundation
- Isabel Haviland
- Affiliation:
Boston Children’s Hospital and Harvard Medical School
- Jennifer A. Kearney
- Affiliation:
Northwestern University Feinberg School of Medicine
- Leah Schust Myers
- Affiliation:
FamilieSCN2A Foundation
- Heather E. Olson
- Affiliation:
Boston Children's Hospital and Harvard Medical School
- Stephan J. Sanders
- Affiliation:
University of Oxford
- Christina SanInocencio
- Affiliation:
FamilieSCN2A Foundation
- Joseph Symonds
- Affiliation:
Royal Hospital for Children and University of Glasgow
- Christopher H. Thompson
- Affiliation:
Northwestern University Feinberg School of Medicine
Summary
SCN2A encodes a voltage-gated sodium channel (designated NaV1.2) vital for generating neuronal action potentials. Pathogenic SCN2A variants are associated with a diverse array of neurodevelopmental disorders featuring neonatal or infantile onset epilepsy, developmental delay, autism, intellectual disability and movement disorders. SCN2A is a high confidence risk gene for autism spectrum disorder and a commonly discovered cause of neonatal onset epilepsy. This remarkable clinical heterogeneity is mirrored by extensive allelic heterogeneity and complex genotype-phenotype relationships partially explained by divergent functional consequences of pathogenic variants. Emerging therapeutic strategies targeted to specific patterns of NaV1.2 dysfunction offer hope to improving the lives of individuals affected by SCN2A-related disorders. This Element provides a review of the clinical features, genetic basis, pathophysiology, pharmacology and treatment of these genetic conditions authored by leading experts in the field and accompanied by perspectives shared by affected families. This title is also available as Open Access on Cambridge Core.