Neurodevelopmental outcomes and clinical utility of genetic testing in a cohort of Australian families with self-limited (familial) epilepsy (neonatal/infantile onset)

Objectives: To clinically phenotype self-limited (familial) neonatal and/or infantile epilepsy syndromes. Firstly, to evaluate i) seizure recurrence ii) neurological co-morbidities and iii) developmental disability. Secondly, to assess clinical utility of genetic testing by determining if genetic diagnoses influence management. Methods: A retrospective cohort study (2011-2022) recruiting families from two paediatric hospitals. Families were included if two first degree relatives with seizures underwent genetic testing. Demographic data and clinical phenotype were assessed. The Vineland Adaptive Behaviour Scales measured adaptive function. A cross-sectional survey of paediatric neurologists assessed impact of genetic testing. Results: Seventeen of twenty-three eligible families consented (73%). Sixteen of seventeen families had a genetic diagnosis; n=13/16 were pathogenic: PRRT2 (n=5), KCNQ2 (n=4), SCN2A (n=4). Three were likely pathogenic: KCNQ2 (n=1), SCN8A (n=2). Seventy-two individuals reported seizures; additional data is available for n=28 children and n=16 adults. Six individuals from four families had seizure recurrence. Paroxysmal kingesiogenic dyskinesia occurred in 3 families (n=1 PRRT2, n=1 SCN2A, n=1 KCNQ2), hemiplegic migraine in 3 families (n=2 PRRT2, n=1 KCNQ2). Four children had Autism Spectrum Disorder with low-average to moderately impaired adaptive functioning. An additional seven children had developmental delay, ranging from isolated speech to moderate global delays. Ninety-two percent (n=23/25) of paediatric neurologists agreed a genetic diagnosis has or would change management. Conclusion: Self-limited (familial) epilepsy syndromes, with neonatal/infantile onset are common and associated with developmental delay, recurrent seizures and neurodevelopmental disorders. Confirmed genetic diagnoses may assist in management and prognostication.
Keywords: Epilepsy, Developmental Delay, Familial, Neonatal, Infantile