SCN1A variants associated with sudden infant death syndrome

We identified SCN1A variants in two infants who died of Sudden Infant Death Syndrome (SIDS) from an exome sequencing study of 10 cases of SIDS with hippocampal abnormalities but no history of seizures. One harbored SCN1A G682V, and the other had two SCN1A variants in cis: L1296M and E1308D, a variant previously associated with epilepsy. Functional evaluation in a heterologous expression system demonstrated partial loss-of-function for both G682V and the compound variant L1296M/E1308D. Our cases represent a novel association between SCN1A and SIDS, extending the SCN1A spectrum from epilepsy to SIDS. Our findings provide insights into SIDS and support genetic evaluation focused on epilepsy genes in SIDS.