SCN1A Overview
• SCN1A is a gene on chromosome 2. It makes part of a brain ion channel (Nav1.1) that helps nerve cells fire. When SCN1Adoes not work properly, brain signals can be too active or not active enough, causing seizures or, in some families, a special type of migraine. Physicians usually order a multi-gene test that looks at many seizure genes at once. This approach finds most SCN1Achanges (called variants).
Genetic Epilepsy with Febrile Seizures Plus (GEFS+)
• Most families have a single-letter change in SCN1A that slightly weakens Nav1.1 in inhibitory brain cells. This makes the brain network easier to trigger, especially with fever. Testing both the child and parents helps estimate the chance of GEFS+ in future children.
Dravet Syndrome (DS)
• Most children have changes that reduce the amount of functional Nav1.1 (loss-of-function). This means that inhibitory brain cells, the neurons that act as the brain’s natural “brakes” on electrical activity, don’t work as well, allowing too much firing between nerve cells and causing seizures (especially with fever/overheating). Testing looks for spelling changes and for missing pieces of the genes. While these spelling errors usually happen in utero, sometimes a parent has the change in only a small fraction of cells (mosaicism).
Familial Hemiplegic Migraine, Type 3 (FHM3)
• Families usually have single-letter changes that make the channel too active (gain-of-function). This lowers the brain’s threshold for a wave of activity called cortical spreading depression – the basis of migraine aura. Testing often looks at other migraine genes (CACNA1A, ATP1A2) at the same time.
Developmental and Epileptic Encephalopathy 6B (DEE6B)
• Many babies have gain-of-function changes that make Nav1.1 over-active from birth. This fits with the very early seizure onset (under 3 months) and different seizure types compared with Dravet syndrome. Physicians recommend early trio testing of the child and both parents, and they may use published lab studies on the exact variant to help choose medicines.
SCN1A