Homozygous PRRT2 mutation causing a spectrum of paroxysmal neurological symptoms responsive to sodium channel blockers

Heterozygous mutations in PRRT2 (proline-rich transmembrane protein 2 gene) cause paroxysmal neurological disorders: paroxysmal kinesigenic dyskinesia, self-limited infantile epilepsy, familial hemiplegic migraine and episodic ataxia. A 36-year-old woman, with related parents and a family history of seizures and migraine, was found in adulthood to be homozygous for PRRT2 frameshift mutations, associated with a broader phenotype. Carbamazepine had controlled convulsions in infancy. When weaned, at nearly 4 years of age, she re-presented with generalised seizures and reduced responsiveness, treated for ‘encephalitis’. Carbamazepine was restarted with full control. In her teens, she reported paroxysmal sensory symptoms of an uncertain nature, which were concluded not to be epileptic. On weaning antiseizure medications at age 17 years, she developed increasing sensory symptoms and hemiplegic migraine, then was admitted with a cerebellar presentation and cerebellar vermis MR T2 hyperintensity. This recovered over weeks, after which she developed focal seizures, now fully controlled on lamotrigine for years. Stability required long-term sodium channel-blocking medication.