Alekhya Narravula (Germany)
InvitaeAuthor Of 2 Presentations
GENETIC TESTING FOR ADULTS WITH EPILEPSY REVEALS A SIGNIFICANT DIAGNOSTIC YIELD AND PRECISION MEDICINE IMPLICATIONS FOR MANY INDIVIDUALS WITH A MOLECULAR DIAGNOSIS
- Dianalee McKnight (United States of America)
Abstract
Background and Aims:
The benefit of genetic testing in children with epilepsy is well-demonstrated, yet little is known about its utility in adults. This study aims to investigate the diagnostic yield and potential precision medicine implications of genetic testing in adults with epilepsy.
Methods:
Genetic testing results from an epilepsy gene panel of up to 186 genes were analyzed for a cohort of 2008 unselected adults (ages 18-78 years, mean 27.8). A definitive, positive molecular diagnosis (PosMD) included either single pathogenic/likely pathogenic (P/LP) variants in autosomal dominant or X-linked genes, or two P/LP (homozygous or compound heterozygous) in recessive genes.
Results:
A PosMD was identified in 221 (11.0%) individuals. Adults with infantile-onset seizures (0-1 years) had the highest PosMD rate (29.6%), followed by early childhood-onset (13.6%, 2-4 years), late childhood-onset (7.0%, 5-10 years), adolescence-onset (2.4%, 11-17 years) and adult-onset (3.7%, ≥18 years). Individuals with epilepsy and intellectual disability and/or developmental delay (ID/DD) had an increased PosMD rate (16.4%). Overall, 54.8% of PosMD individuals had findings in genes with precision medicine implications (PMI-genes, e.g., SCN1A, TSC1, KCNQ2, and SCN2A). Among individuals with pharmacoresistant epilepsy, 13.5% had a PosMD, of which, 57.4% were in PMI-genes.
Conclusions:
Genetic testing has a significant PosMD yield for adults with epilepsy. Nearly half of PosMD are in PMI-genes, suggesting that genetic testing could have a direct impact on clinical management. Genetic testing should be broadly considered in adults, particularly for those with infancy/childhood-onset seizures or with ID/DD.
GENETIC TESTING GUIDES CLINICAL MANAGEMENT OF EPILEPSY AND IMPROVES PATIENT OUTCOMES
- Dianalee McKnight (United States of America)
Abstract
Background and Aims:
Nearly half of positive genetic testing findings for epilepsy are in clinically actionable genes and can help guide clinical management. However, little information is available on how genetic information is used by clinicians to guide management and what the patient outcomes are. In this study, we addressed this gap by investigating changes in clinical management and patient outcomes after a definitive genetic diagnosis of epilepsy was identified.
Methods:
Between May-November 2020, 170 of 1,567 invited clinicians completed case report forms for 429 patients with epilepsy and a positive genetic diagnosis.
Results:
In 49.9% of cases (n=214), the positive genetic diagnosis led to a change in clinical management. In most cases (81.3%, n=174), providers changed clinical management within 3 months of receiving the genetic result. Over half of the reported clinical management changes pertained to medication adjustments. Of those who were followed up on after treatment change (n = 172), 75% (n = 129) were reported to have improvement in their condition. Specifically, 65% (n=111) of patients had improved seizure control (reduced or stopped seizures).
Conclusions:
Our study demonstrates that genetic testing can enable critical clinical management changes that improve patient outcomes. Previous patient studies demonstrated reduced healthcare costs for individuals with good seizure management compared to individuals with poor seizure control (~$14,000/year vs. ~$23,000/year, respectively), due to decreased hospitalizations and emergency department visits. Collectively these data can inform updates to guidelines to include genetic testing to improve health outcomes, and ultimately reduce healthcare costs.