Compound heterozygosity with PRRT2: Pushing the phenotypic envelope in genetic epilepsies

PRRT2 pathogenic variants have been described in benign familial infantile epilepsy, episodic ataxia, paroxysmal kinesigenic dyskinesia, and hemiplegic migraines.

We describe a patient with compound heterozygous variants, infantile epilepsy with status epilepticus, paroxysmal dyskinesia and episodic ataxia.

Testing revealed a pathogenic PRRT2 duplication (c.649dupC), and a likely pathogenic missense variant (c.916G>A).

His presentation meets the severe phenotypic category with a combination of at least 3 neurological symptoms: seizures and status epilepticus, prolonged episodic ataxia, and paroxysmal dyskinesia. This further expands the clinical findings related to PRRT2, and suggests that compound heterozygous variants could confer a severe phenotype.