Rationale:
KCNT1-related epilepsy is a severe, often treatment-resistant epileptic encephalopathy linked to variants in the KCNT1 gene. Understanding the genetic and clinical variability within this patient population is crucial for advancing treatment strategies and improving patient outcomes. This study provides a detailed analysis of demographic, genetic, seizure, developmental, and clinical data from a cohort of 46 patients with KCNT1-related epilepsy, aiming to identify patterns that may inform future research and therapeutic approaches.
Methods:
Data were collected from 46 patients diagnosed with KCNT1-related epilepsy who submitted their medical information to Citizen, a patient-driven data sharing platform that allows individuals to securely store and share their health records for research purposes. Demographic data, including gender and age at diagnosis, were analyzed. Clinical data encompassed a wide range of diagnostic codes associated with neurological, motor, respiratory, gastrointestinal, cardiovascular, sensory, genitourinary, and other systemic functions, as well as specific data on seizure frequency, type, and severity. Developmental data were also examined to assess the impact of KCNT1 variants on cognitive and motor milestones.
Results:
The cohort consisted of 20 females and 25 males, with a median age at diagnosis of 106 days. All patients had confirmed variants in KCNT1, with 4% exhibiting multiple KCNT1 variants. Of the 48 variants identified, 34 were known pathogenic, 8 were likely pathogenic, and 6 were of uncertain significance. Clinically, 490 diagnostic codes were recorded, with 25% related to motor and musculoskeletal function, followed by respiratory (17.6%) and neurological/cognitive function (20%). Seizure data indicated that the majority of patients experienced frequent, treatment-resistant seizures, with a wide range of seizure types observed. Developmental data revealed significant delays in cognitive and motor milestones across the cohort, with varying degrees of severity.
Conclusions:
This study highlights the clinical complexity and heterogeneity of KCNT1-related epilepsy. The extensive range of clinical diagnoses highlights the multi-systemic impact of KCNT1 mutations, reinforcing the need for multidisciplinary management strategies. Future work should focus on integrating genetic and clinical data to develop personalized treatment approaches for KCNT1-related epilepsy.
Funding: This research was supported by the KCNT1 Epilepsy Foundation.