Variable Phenotypes in the Same Patient with PRRT2-Associated Disorders

Abstract

Mutations in the PRRT2 gene lead to a spectrum of diseases with a commonpathophysiology including self-limited (familial) infantile epilepsy and paroxysmalkinesigenic dyskinesia as well as other paroxysmal diseases involving movement andheadache disorders. Atypical phenotypes, associated with episodic ataxia, epilepsy,hemiplegic migraine, developmental delay, and intellectual disability, have beenreported in approximately 5% of the patients, which is probably an underestimation.Here, we present three patients with variable PRRT2 phenotypes in each patient. In thefirst two patients, the manifestations were characterized by episodes of nonepilepticparoxysms and focal seizures starting in the first years of life with good response tocarbamazepine. One of them had no family history either of epilepsy or nonepilepticmotor manifestations. The other patient simultaneously developed epileptic spasms.Neurodevelopment was normal in both. The third patient presented with early-onsetfocal epilepsy that was resistant to antiseizure medications and evolved to spike-waveactivation in sleep associated with cognitive impairment and ataxia. In this patient, inaddition to the mutation in the PRRT2 gene, a novel pathogenic SCN1A variant wasidentified. The distinct clinical presentations in the same patient observed in our casesconfirm the broad spectrum of PRRT2-associated diseases.