SCN1B-related disorders are caused by pathogenic variants in the SCN1Bgene, which encodes for the voltage gated sodium channel beta 1 subunits. Different variant types and inheritance patterns have been reported including missense variants with incomplete penetrance that often cause the GEFS+ or Brugada syndrome phenotypes vs homozygous variants more often resulting in complete loss of function and a Dravet Syndrome or DEE type phenotype. However, these are not absolute rules and Dravet Syndrome and DEE phenotypes have been seen with missense variants as well. While this condition is mainly thought to represent a loss of function type of impairment to the channel, there are isolated reports of variants which appear to have a gain of function type effect and respond to sodium channel blockade. There is new evidence that dysregulation of SCN1Bis among several genes which contribute to the neuronal excitation/inhibition imbalance in autism. As more is learned about this mechanism SCN1B may become a key gene in autism phenotypes as well.
SCN1B