Pediatric Epilepsy Genomic Results Should Be Reinterpreted Regularly

Jason Park, MD, PhD

In a new report reinterpreting clinical genomic epilepsy test results, about a third of patients had variants reclassified. This led to a clinically significant change in the interpretation in a third of that cohort.

Investigators from the University of Texas Southwestern Medical Center retrospectively reviewed 309 pediatric epilepsy screenings in order to examine the value of reinterpreting previously reported genomic test results. The patients underwent genomic epilepsy testing at a single tertiary care pediatric health care facility between July 2012 and August 2015. The investigators wondered how often genomic test result interpretations change, and so the reinterpretation took place in May 2017.

Genomic testing is used to judge several pediatric neurological diseases, the study authors said. While recent studies have focused on the discovery and identification of new disease relationships using the genomic data, only a few studies have looked into the scope of re-analysis to include all the gene variants of previously reported conditions.

The patients involved in the study had a mean age of 5.6 years and half were male. All reported genetic variants were reexamined using the 2015 consensus standards and guidelines used for interpreting hereditary genetic variants, the study authors explained. They used 3 classification tiers in the reinterpretation: pathogenic or likely pathogenic variant; variant of uncertain significance (VUS); or benign or likely benign variant.

There were 185 patients with a genetic variant that was reported. From there, the investigators pinpointed 61 patients with a genetic diagnosis, leaving 124 patients without.

By reinterpreting the reported variants, 67 of the 185 patients (36.2%) had a change in their variant classification, the study authors reported. Of that group, a third of the patients received a change of diagnosis.

“Before we began the study, I suspected that over time advances in medical knowledge would lead to changes in some genetic test interpretations,” study author Jason Park, MD, PhD told MD Magazine®. “However, in the present study, I was surprised that the percent of cases with a change in diagnosis exceeded 30%. I believe that interpretation of genetic tests is not a onetime event, but it is a dynamic process that should be re-performed on a periodic basis.”

Across the 5-year study period, 31% of the patients with a genetic diagnosis and 38% of the patients with undiagnosed conditions had their results reclassified, the investigators found.

When the study authors reviewed the genomic reports issued during the final 2 years of the study period, they observed a reclassification of variants in 4 of the 15 patients considered to have a pathogenic or likely pathogenic variant. There was a reclassification among 11 of the 41 patients with a VUS, they added.

“For patients with epilepsy, genetic testing is a powerful tool which is not only diagnostic, but can identify effective therapies,” Park continued. “Physicians should know that the interpretation of their patients’ genetic test results may change over time.”

Park said that physicians should consider asking laboratories to reinterpret previously reported genetic test results in a few scenarios, such as:

• when a period of 13 years has elapsed from the initially reported results;
• when they are considering making changes to a patient’s medication or other therapies;
• when they are considering ordering further genetic testing.

The paper, “Clinical Utility of Reinterpreting Previously Reported Genomic Epilepsy Test Results for Pediatric Patients,” was published in JAMA Pediatrics.