The economic burden of KCNT1-related disorders in the United States: insights from caregiver-reported and EMR-derived data

KCNT1-related disorders are rare, severe neurogenetic disorders associated with early-onset, treatment-resistant seizures and significant developmental comorbidities. Currently there are no treatment-modifying therapeutics for this condition, and the condition necessitates complex, lifelong care that places a profound financial strain on affected families and healthcare systems. However, data quantifying this economic burden is sparse. To evaluate the annual cost burden of KCNT1-related disorders in the United States using both caregiver-reported expenditures and electronic medical record (EMR) data, providing a comprehensive analysis of direct, indirect, and out-of-pocket expenses. A retrospective cohort analysis was conducted using two complementary data sources. In 2025, 34 U.S-based caregivers from the KCNT1 Epilepsy Foundation registry completed a survey capturing insurance status, medical and non-medical expenses, and indirect costs. Separately, EMR data from 49 U.S.-based patients with KCNT1 variants were extracted from the Citizen Health database. Clinical services were mapped to CPT and HCPCS codes, and costs were calculated using Medicare fee schedules and other publicly available datasets. Caregiver-reported data revealed that all respondents possessed some form of insurance coverage, primarily through private insurance purchased independently or through their employer, or Medicaid. Nearly half of respondents (18/34) experienced financial hardship, citing high out-of-pocket expenses, medical debt, and loss of income due to caregiving responsibilities, and twelve percent of respondents delayed treatment due to financial strain (n = 4). The estimated mean total annual medical cost per family—including direct, indirect, non-medical, and non-covered expenses—ranged from $355,474 to $797,727, based on upper and lower bounds of response categories from 10 respondents. EMR analysis, which only reported on direct medical costs, revealed that average first-year direct medical costs reached $154,389 per patient based on the records from 49 patients. This cost was primarily driven by hospitalizations, medications, and therapeutic procedures. Based on EMR data, direct medical costs declined once the patients reached two years of age and stabilized in subsequent years. Hospitalizations remained the most substantial cost contributor regardless of the age of the patient. KCNT1-related disorders impose a substantial economic burden on families and healthcare systems, particularly in the first year after diagnosis. This study highlights the need for rapid diagnostic procedures, targeted therapies, improved insurance coverage, and legislative support for families managing rare, high-burden conditions. These findings provide essential cost data to support drug development, healthcare planning, and rare disease policy reform. This is the first U.S.-based study to quantify both medical and non-medical costs associated with KCNT1-related disorders using combined caregiver and EMR data. The results highlight the urgency of disease-modifying treatments and equitable access to care, informing clinical trials and advocacy for systemic healthcare support.