Phenotype diversity in patients with PRRT2 gene variant: Case series report

Abstract

Objectives Pathogenic variants in the PRRT2 (proline-rich transmembrane protein 2) gene have been identified as the main cause of an expanding spectrum of disorders, including paroxysmal kinesigenic dyskinesia and benign familial infantile epilepsy, which places this gene at the border between epilepsy and movement disorders. The clinical spectrum has largely expanded to include episodic ataxia, hemiplegic migraine, and complex neurodevelopmental disorders in cases with biallelic mutations. In this case series report we would like to explore clinical symptoms for patients with PRRT2 gene variant. Materials and Methods We report 8 patients (1 male and 7 females) from 4 different families. Each family had one member diagnosed with early onset epilepsy undergo whole exome sequencing with epilepsy gene virtual panel. Other family members were tested by targeted Sanger sequencing. The most common PRRT2 gene pathogenic variant NM_145239.3:c.649del was confirmed for all patients. Results 6/8 patients had early onset epileptic seizures (median age 5 months) which responded well to standard treatment. 4 patients are on medication at the analysis time and 3 patients were prescribed valproic acid and one patient uses phenytoin. 6/8 of these patients had appropriate development for age. 2/8 patients have autistic traits and intellectual disability with psychiatric disease possibly caused by other reasons. Seizures resolved without treatment in one case. 2 adult patients have symptoms of hemiplegic migraine that started in the teenage years. One patient had seizures as a baby and now involuntary movements were noticed in adulthood. Conclusions We confirm that PRRT2 gene variants cause wide range of symptoms: familial benign epilepsy, hemiplegic migraine and movement disorder. Treatment with valproic acid was effective for our patients. It is very important to properly recognize families with possible PRRT2 gene variants to hasten and optimize genetic testing.