Abstracts

Rationale: In order to optimize clinical use, this study aimed to determine what patient characteristics are most predictive of a pathogenic or likely pathogenic result from epilepsy gene panel testing.Methods: The study evaluated Boston Children’s Hospital patients (N= 131) who had epilepsy gene panel testing in a CLIA laboratory between 6/2012 and 10/2014. Patient records were reviewed and data collected for diagnostic test results and clinical characteristics. For the purpose of this study, we defined a positive result as an identified variant in an epilepsy gene interpreted clinically as a likely or possible explanation for the patient’s neurologic phenotype. Predictor variables included the following: age of epilepsy onset, epilepsy type, seizures types, seizure frequency, status epilepticus, tendency for seizure clusters, EEG encephalopathy pattern, brain malformation and type, gestational age, epilepsy in a first degree relative, developmental disorder, developmental regression, cortical visual impairment, movement disorder, muscle tone, and head size. Following univariate analysis, logistic regression modeling was used to evaluate for the strongest predictors of a positive result while accounting for confounding, using a purposeful selection technique.Results: The overall probability of a positive epilepsy gene panel result was 48%. In a multivariate logistic regression model the significant predictors of positive epilepsy gene test were limited to age at epilepsy onset and tonic-clonic seizures (Table 1, Figure 1). The odds of a positive epilepsy gene panel result was 9.5 times higher in patients with epilepsy onset at ≤ 2 years compared to patients with epilepsy onset after 2 years, 95% confidence interval [3.0, 30.5], adjusted for tonic-clonic seizures. The odds of a positive epilepsy gene panel result was 2.3 times higher in patients with tonic-clonic seizures compared to patients without tonic-clonic seizures, 95% confidence interval [1.0, 5.1], adjusted for age of epilepsy onset. There was no effect modification by spasms, muscle tone or developmental disorder. Age of epilepsy onset was then divided into 4 groups, quartiles in the study base rounded to clinically meaningful values. There was a clear trend with higher odds of a positive result the younger the age of epilepsy onset (p<0.001). The odds of a positive test result was 12.2 times higher in patients with epilepsy onset at ≤ 0.25 years, 10.6 times higher in patients with epilepsy onset at >0.25 to ≤ 0.75 years, and 9.7 times higher in patients with epilepsy onset at >0.75 to ≤ 1.5 years, each compared to patients with epilepsy onset at >1.5 years, adjusted for tonic-clonic seizures.Conclusions: With a 48% yield of positive results, epilepsy gene panel testing was not over-used. While diagnostic for a variety of seizure types and epilepsy syndromes including infantile spasms, younger age of epilepsy onset and tonic-clonic seizures were statistically most predictive of a positive epilepsy gene panel result in a clinically relevant series.