Marked Improvement in Epilepsy, Movement Disorder and Behaviour in a Child With CDKL5 Deficiency Disorder Treated With Ganaxolone and Fenfluramine: A Case Report

CDKL5 deficiency disorder (CDD) is a severe developmental and epileptic encephalopathy characterised by early-onset, treatment-resistant seizures and severe neurodevelopmental impairment.Ganaxolone is approved for the treatment of seizures associated with CDD, while fenfluramine has shown potential antiseizure activity in a small series of patients with CDD.We report the case of a girl with CDD who experienced a marked and partially sustained clinical response to combination therapy with ganaxolone and fenfluramine.Ganaxolone reduced major motor seizure frequency by approximately 50-60%, with additional improvements in alertness, responsiveness, mood, communication and motor development.Following the addition of fenfluramine, motor seizures ceased for eight weeks before recurring at a lower frequency after a febrile illness.Overall, combination therapy was generally well tolerated, although dose escalation was limited by somnolence, which resolved promptly following dose reduction.Serial echocardiograms remained normal.Complete long-term seizure control and EEG normalisation were not achieved.This case suggests that combined ganaxolone and fenfluramine therapy may provide benefits beyond seizure reduction in CDD, including improvements in development, behaviour and overall quality of life, and warrants further investigation.