PRRT2: A major cause of infantile epilepsy and other paroxysmal disorders of childhood

In the past 2 years, mutations in the PRRT2 gene have been identified in patients and families with a variety of early-onset paroxysmal disorders, including various paroxysmal dyskinesias, benign familial infantile seizures, hemiplegic migraine, and episodic ataxia. In this chapter, we describe the wide clinical spectrum associated with PRRT2 mutations and present the current hypotheses on the underlying pathophysiology. Through its interaction with the presynaptic plasma membrane protein SNAP25, the PRRT2 protein may play a role in synaptic regulation in the cortex and basal ganglia. PRRT2 mutations likely have a loss-of-function effect and result in synaptic deregulation and neuronal hyperexcitability. The molecular bases underlying phenotypic variability are still unclear. Elucidating the molecular pathways linking the genetic defect to its clinical expression will improve treatment of these disorders.