Genetic Diagnosis in Pediatric Epilepsy Impacts Medical Management

Abstract number : 2.319
Submission category : 12. Genetics / 12A. Human Studies
Year : 2021
Submission ID : 1826579
Source : www.aesnet.org
Presentation date : 12/5/2021 12:00:00 PM
Published date : Nov 22, 2021, 06:54 AM

Authors :
Isabel Haviland, MD - Boston Children's Hospital/Harvard Medical School; Carolyn Daniels, BA – Boston Children's Hospital; Caitlin Greene, BS – Boston Children's Hospital; Jacqueline Drew, MS – Boston Children's Hospital; Jamie Love-Nichols, MS, MPH, CGC – Seattle Children's Hospital; Lindsay Swanson, MS, CGC – Boston Children's Hospital; Lacey Smith, MS, CGC – Boston Children's Hospital; Beth Sheidley, MS, CGC – Boston Children's Hospital; Bo Zhang, PhD – Boston Children's Hospital; Annapurna Poduri, MD, MPH – Boston Children's Hospital; Heather Olson, MD, MS – Boston Children's Hospital

Rationale: Genetic diagnosis in epilepsy increasingly has implications for medical care, but direct impact on management in a clinical setting has not been measured1. We aimed to assess individualized medical impact of genetic diagnosis in a cohort of patients with infantile or childhood-onset epilepsy.

1. Striano, P; Minassian, BA. From Genetic Testing to Precision Medicine in Epilepsy. Neurotherapeutics. 2020;17(2):609-615.

Methods: We evaluated a cohort of individuals with infantile or childhood-onset epilepsy at Boston Children’s Hospital (BCH) who received a genetic diagnosis by next-generation sequencing between 2012 and 2019, all with an epilepsy gene panel with or without exome. We reviewed medical records to determine impact of results on medical management according to the following categories: treatment, care coordination and diagnostic testing, prognosis, and change in diagnosis.

Results: Our cohort consisted of 152 individuals (46% F, median age of onset 6 months [IQR 2 to 15 months]) with a clinical diagnosis of genetic epilepsy, out of 602 individuals with infantile or childhood-onset epilepsy who underwent next-generation sequencing. Genetic diagnosis as summarized in Figure 1 had a direct impact on medical management in at least one category for 72% of patients (110/152), and in more than one category in 34% (51/152). Treatment was impacted in 45% of individuals, including 36% with impact on anti-seizure medication choice, 7% on use of disease-specific vitamin or metabolic treatments, 3% on pathway-driven off-label use of medications, and 10% on discussion of gene-specific clinical trials (Table 1, including case examples). Care coordination was impacted in 48% of individuals, including surveillance for disease-associated features (e.g. later-onset symptoms), disease-specific diagnostic testing (e.g. to evaluate for systemic disease involvement) and specialist referrals or disease-specific multi-disciplinary clinics. Counseling on a change in prognosis was reported in 28% of individuals (e.g. degenerative disease), and 1% of individuals had a change in diagnosis.

Conclusions: Of the 25% of our cohort of individuals with unexplained infantile or childhood-onset epilepsy who received a genetic diagnosis, we demonstrated meaningful impact on medical care and prognosis beyond recurrence risk counseling in over 70% of cases. These results support the routine use of genetic testing as part of the standard evaluation for patients with unexplained epilepsy to optimize and individualize treatment, prognosis and coordination of clinical care.

Funding: Please list any funding that was received in support of this abstract.: National Institute of Neurologic Disorders and Stroke (K23 NS107646-04, PI Olson) and the Children’s Rare Disease Cohort Initiative at BCH.