Prrt2-Related Infantile Epilepsy: Not That ‘Benign”: Developmental Delays and Autistic Features Are Common!

Background: PRRT2-related epilepsy in neonates and infants has been considered to have good long-term outcome. The developmental delays have not been described in this population. We describe a cohort of children with PRRT2-related epilepsy having developmental delays. Study methods: Descriptive, observational study of genetically confirmed children with PRRT2-related epilepsy Results: Twenty children included; clinical details given in table 1. The commonest seizure type was multifocal, clonic seizure (18 of 20; 90%), followed by focal-onset, non-motor seizure in 2, epileptic spasms in one. Seizure clustering was seen in 10 children (50%). At baseline, all children had normal head circumference, developmental delay in 4 children (20%), abnormal neurological examination in 2 (central hypotonia and spasticity). Commonest 1st line anti-seizure medication (ASM) used was Levetiracetam (19 of 20; 95%), while Phenobarbitone was the commonest 2nd-line ASM used. Nineteen children had pathogenic/likely pathogenic variations in PRRT2, and VUS in one child. At mean follow-up of 22.9 months age (range 5.5-60), all children were seizure-free for mean period of 11.9 months (range 1-48 months). At follow-up, developmental delay was noted in 11 children (55%): motor delay in 6 (30%), language delay in 9 (45%) and social delay in 7 (35%). Ten of these children were receiving rehabilitation for delay. Notably, four children had autistic features (20%) which is far higher than in general population. Conclusion: Although seizures are usually well controlled, significant number of children with PRRT2-related epilepsy have developmental delays and autistic features. This is important in prognostication and planning early intervention services.