Caregiver perspectives on disease burden and treatment priorities in KCNT1-related disorders.
L’essentiel
BACKGROUND Pathogenic variants in KCNT1, encoding the sodium-activated potassium channel KNa1.1 (Slack), cause severe developmental and epileptic encephalopathies marked by early-onset, treatment-resistant seizures and profound neurodevelopmental impairment. While clinical and electrophysiological features are well described, systematic caregiver-reported data on treatment effectiveness and family impact are limited. METHODS The KCNT1 Epilepsy Foundation established an international online caregiver-reported registry. Caregivers of individuals with a clinical and/or genetic diagnosis of a KCNT1-related disorder completed structured surveys between April 2023 and January 2024. Data included demographics, genetic variants, seizure characteristics, treatment history, sleep behaviors, quality of life, and family impact using validated and custom instruments. RESULTS Data from 62 individuals across 13 countries were analyzed. Seizure onset was early (median: 1 month), with diagnosis occurring shortly thereafter (median: 4 months). Sixteen distinct KCNT1 missense variants were reported across the cohort. Caregivers reported a high treatment burden, with a median of 2.5 concurrent antiseizure therapies. The ketogenic diet, clobazam, phenobarbital, and levetiracetam, and vagus nerve stimulation were perceived as highly beneficial, while many conventional antiseizure medications showed limited benefit or worsening. Profound challenges were reported, particularly in cognitive and physical functioning, along with substantial emotional and practical family burden. Treatment priorities extended beyond seizure control to include communication, overall health, and quality of life, with notable gaps between priorities and perceived effectiveness. CONCLUSIONS Caregiver-reported data demonstrate severe burden and substantial unmet needs in KCNT1-related disorders, highlighting the importance of patient- and family-centered outcome measures in care and therapeutic development.
Synthèse détaillée
Résumé original
BACKGROUND Pathogenic variants in KCNT1, encoding the sodium-activated potassium channel KNa1.1 (Slack), cause severe developmental and epileptic encephalopathies marked by early-onset, treatment-resistant seizures and profound neurodevelopmental impairment. While clinical and electrophysiological features are well described, systematic caregiver-reported data on treatment effectiveness and family impact are limited. METHODS The KCNT1 Epilepsy Foundation established an international online caregiver-reported registry. Caregivers of individuals with a clinical and/or genetic diagnosis of a KCNT1-related disorder completed structured surveys between April 2023 and January 2024. Data included demographics, genetic variants, seizure characteristics, treatment history, sleep behaviors, quality of life, and family impact using validated and custom instruments. RESULTS Data from 62 individuals across 13 countries were analyzed. Seizure onset was early (median: 1 month), with diagnosis occurring shortly thereafter (median: 4 months). Sixteen distinct KCNT1 missense variants were reported across the cohort. Caregivers reported a high treatment burden, with a median of 2.5 concurrent antiseizure therapies. The ketogenic diet, clobazam, phenobarbital, and levetiracetam, and vagus nerve stimulation were perceived as highly beneficial, while many conventional antiseizure medications showed limited benefit or worsening. Profound challenges were reported, particularly in cognitive and physical functioning, along with substantial emotional and practical family burden. Treatment priorities extended beyond seizure control to include communication, overall health, and quality of life, with notable gaps between priorities and perceived effectiveness. CONCLUSIONS Caregiver-reported data demonstrate severe burden and substantial unmet needs in KCNT1-related disorders, highlighting the importance of patient- and family-centered outcome measures in care and therapeutic development.