Jody Westbrook (United States of America)
Invitae Department of Medical AffairsAuthor Of 1 Presentation
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.