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Genetic testing affected the medical care of nearly three of four children with unexplained epilepsy, a study of patients with infantile or childhood-onset seizures showed.

A genetic diagnosis had a direct impact on medical management in at least one category for 72% of patients and in more than one category in 34%, reported Isabel Haviland, MD, of Boston Children's Hospital, at the American Epilepsy Society annual meeting, which is being held in Chicago and online.

"The impact of genetic diagnosis on medical management was substantial in our cohort of 152 individuals with pediatric epilepsy," Haviland told 番茄社区.

"Care coordination and treatment were impacted in nearly half of participants, and prognosis changed in nearly one-third of individuals," she said. "Impact was highest in those with earlier age of epilepsy onset -- age 2 or younger -- but was also significant in those with later age of onset."

"Impact was observed both in those with developmental disorders and in those with normal development," Haviland added. "Genetic testing should be included as part of the standard evaluation of individuals with unexplained pediatric epilepsy, as a means of achieving diagnostic precision and informing clinical management."

The study is the first to report of the effect of a genetic diagnosis of medical managment of pediatric epilepsy in the clinical setting. It looked at 152 pediatric patients at Boston Children's Hospital with a clinical diagnosis of genetic epilepsy, out of 602 patients with infantile or childhood-onset epilepsy who underwent next-generation sequencing between 2012 and 2019. Of the 152 children included in the analysis, 46% were girls and median age of onset was 6 months.

A genetic diagnosis affected at least one of four categories of medical management, including care coordination (48%), treatment (45%), counseling about a change in prognosis (28%), and change in diagnosis (1%).

Care coordination changes included surveillance for disease-associated features such as later-onset symptoms, disease-specific testing to evaluate for systemic disease involvement, and referrals to specialists or disease-specific multidisciplinary clinics.

Treatment changes included:

• Anti-seizure medication choice for 36% of patients
• Gene-specific vitamin or metabolic treatments for 7%
• Pathway-driven off-label drugs for 3%
• Discussion of gene-specific clinical trials for 10%

A change in treatment course can make a significant difference in a child's life, Haviland noted. Vitamin B6 is important for brain development, for example, but some genetic disorders affect its pathway. Supplements or related vitamins may partially correct the problem and treat the epilepsy.

In the study, one child was found to have a PRRT2 variant with benign familial infantile seizures and was treated with oxcarbazepine (Trileptal) with excellent response. Another patient was found to have a variant in the GRIN2A gene and was treated with memantine (Namenda) -- which is FDA approved for Alzheimer's disease -- a switch that wouldn't have been considered without a genetic diagnosis.

"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," Haviland and colleagues noted in their presentation. "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."

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