Abstracts

Rationale: Genetic testing has become a routine part of the diagnostic process for patients with unexplained epilepsy and the number of genes with direct treatment or management implications continues to grow.¹ However, many patients have difficulty accessing testing due to insurance or other barriers. Delays in testing can impact the treatment and outcomes of patients who could benefit from targeted therapies.² We aimed to assess the extent of and the reasons for delays in obtaining a genetic diagnosis in pediatric patients with epilepsy followed at or referred to a tertiary care center with an epilepsy genetics specialized program.

Methods: We assessed a cohort of 94 patients with epilepsy at Boston Children’s Hospital who received a genetic diagnosis associated with clinically available targeted therapy (Table 1). We excluded conditions for which only experimental treatments are available.¹ We included patients born after 2003. We reviewed medical records to identify any barriers to obtaining genetic testing and whether these barriers caused a delay in diagnosis and medical management.

Results: In our cohort of 839 patients diagnosed with genetic epilepsy, 94 had a pathogenic or likely pathogenic variant in a gene with an established treatment recommendation (44% F, median epilepsy onset age 4 months). Average time to diagnosis after onset was 2.7 years (median=1 year). Patients were divided into 2 groups: 1- those with seizure onset before 2015 and 2- those with onset after; reflecting the increased availability of testing. Out of the 38 individuals in group 2, 12 (32%) had barriers to testing, including insurance (n=10, 26%) and access to testing (e.g., locally unavailable) (n=4, 11%). Out of those 12, 8 (67%) had changes to their treatments after diagnosis (the remaining 4 already had well-controlled seizures or were on an effective anti-seizure medication). For example, insurance denied testing twice for a 3-year-old with delays, regression, and new epilepsy whose final genetic diagnosis was neuronal ceroid lipofuscinosis type II, delaying the start of intra-ventricular enzymatic replacement (cerliponase alpha). Also, sodium channel blockers were used in 3 children (25%) prior to diagnosis with SCN1A-related epilepsy, causing significant seizure worsening in 2. Their use was also imminent in at least one patient prior to receiving the SCN1A diagnosis.

Conclusions: Despite increased understanding of both clinical and personal utility (e.g., family planning) of genetic testing in the epilepsies, patients and providers still face challenges in obtaining testing. This can result in delays in diagnosis and the use of available gene-based therapies.

References:
_x000D_ 1. Zimmern et al. A Review of Targeted Therapies for Monogenic Epilepsy Syndromes. Front Neurol 2022;13:829116._x000D_ 2. Gall et al. Next-generation sequencing in childhood-onset epilepsies: Diagnostic yield and impact on neuronal ceroid lipofuscinosis type 2 (CLN2) disease diagnosis. PLoS One 2021;16:e0255933._x000D_
Funding: The Children’s Rare Disease Cohort Initiative at BCH