Diagnostic delay in infants with very early‐onset rare and ultra‐rare genetic epilepsies
Chiara Pizzuto, Valeria Morabito, Evelina Carapancea, Maria Roberta CilioAbstract
Aim
To evaluate time to diagnosis in infants with very early‐onset genetic epilepsies, identify contributing factors to diagnostic delay, and assess the impact of a definite diagnosis on clinical management.
Method
Infants with genetic epilepsies and seizure onset before 3 months of age were retrospectively identified from a cohort of 500 children with epilepsy followed at Saint‐Luc University Hospital, Belgium, between 2018 and 2025. A correct diagnosis was defined as recognition of electroclinical phenotype before or at genetic confirmation. Diagnostic delay was defined as time to diagnosis exceeding 4 weeks from seizure onset.
Results
Thirty infants with KCNQ2/3‐, SCN2A‐, SCN1A gain‐of‐function, CDD‐, BRAT1‐, KCNT1‐, FGF12‐, SMC1A‐, STXBP1‐, GNAO1‐, PHF6‐, CELF2 ‐ , and 2q24.3 microduplication‐related epilepsies were included. Median time to diagnosis was 55 days (interquartile range 30–427). Twenty‐four patients (80%) experienced more than 4 weeks' delay. The correct diagnosis prompted change in management in 25 infants (83%). Contributing factors included deferred diagnosis by paediatric neurologists (79%), unreported/undescribed phenotypes in ultra‐rare epilepsies (33%), misinterpretation of ictal events by paediatricians (17%), and parental underestimation of events (13%).
Interpretation
Diagnostic delay in infants with rare epilepsies is a major issue, even in a universal health care context, mainly driven by mischaracterization of seizure semiology by paediatric neurologists.