Genetic Testing Found Causes In Many Children With Epilepsy

What was studied

Researchers evaluated how useful next-generation sequencing was for identifying genetic causes of epilepsy in 250 children in Turkey whose epilepsy did not have a known cause. The children were assessed between January 2021 and December 2024. Of the 250 children, 104 had whole-exome sequencing and 146 had clinical exome sequencing.

The team retrospectively reviewed each child’s seizure semiology, brain imaging, EEG findings, and treatment response. Genetic changes were classified using ACMG guidelines to determine whether they were pathogenic, likely pathogenic, or uncertain.

What they found

A definitive molecular diagnosis was found in 89 of 250 children, or 35.6%. When the researchers also included variants of uncertain significance with strong phenotypic correlation, the yield increased to 57.6%, but those cases were not all definitive diagnoses.

The genetic findings were highly heterogeneous, with 59 different genes involved. SCN1A was the most frequently implicated gene, followed by MECP2 and PRRT2. A specific PRRT2 variant was identified in four unrelated Turkish families. Among confirmed diagnoses, most were autosomal dominant, with smaller numbers of autosomal recessive and X-linked conditions.

Whole-exome sequencing and clinical exome sequencing had similar diagnostic yields. Neonatal-onset epilepsy and the presence of autistic features were significantly associated with a positive genetic diagnosis.

Limits of the evidence

This was a retrospective study from a single center, so the results may not apply in the same way to other settings or populations. The study included only children with epilepsy of unknown cause, which may affect how often a genetic diagnosis was found.

The higher 57.6% number includes variants of uncertain significance with strong phenotypic correlation, so that number should not be interpreted the same way as a confirmed diagnosis. The abstract also does not report how often the genetic results changed treatment or long-term outcomes.

For families and caregivers

This study suggests that exome-based genetic testing found a definitive genetic cause in about 1 out of 3 children with unexplained epilepsy in this setting. A genetic answer may help explain the condition and support genetic counseling, although this abstract does not show how often treatment changed.

It also shows that genetic findings can vary across populations, and some variants may recur within a region. For families, this supports asking whether genetic testing is appropriate when a child has epilepsy without a clear cause, especially if seizures began in the neonatal period or there are autistic features.

What to watch next

Future studies could test these findings in multiple centers and examine how often genetic results affect treatment, prognosis, and family counseling.

Terms in this summary

exome sequencing

A genetic test that looks at the parts of genes most likely to affect how the body works.

whole-exome sequencing

A broad exome test that examines many genes across most of the exome.

clinical exome sequencing

An exome-based test focused on genes most relevant to known medical conditions.

variant

A change in DNA.

pathogenic

A DNA change known to cause disease.

variant of uncertain significance

A DNA change where it is not yet clear whether it causes disease.

autosomal dominant

A condition that can happen when a person has one disease-causing copy of a gene.

autosomal recessive

A condition that usually happens when a person has two disease-causing copies of a gene, one from each parent.