Atypical course in individuals from Spanish families with benign familial infantile seizures and mutations in the PRRT2 gene

• We describe atypical features in a high percentage of the patients with BFIS.
• We suggest to perform a long-term follow-up in patients without a benign outcome.
• We also extend the mutational spectrum of PRRT2.

SummaryA benign prognosis has been claimed in benign familial infantile seizures (BFIS). However, few studies have assessed the long-term evolution of these patients. The objective of this study is to describe atypical courses and presentations in BFIS families with mutations in PRRT2 gene.We studied clinically affected individuals from five BFIS Spanish families. We found mutations in PRRT2 in all 5 families.A non-BFIS phenotype or an atypical BFIS course was found in 9/25 (36%) patients harbouring a PRRT2 mutation. Atypical features included neonatal onset, mild hemiparesis, learning difficulties or mental retardation, and recurrent seizures during adulthood. We also report a novel PRRT2 mutation (c.121_122delGT).In BFIS families an atypical phenotype was present in a high percentage of the patients. These findings expand the clinical spectrum of PRRT2 mutations including non-benign epileptic phenotypes.