Diagnostic Yield of Epilepsy Panel Testing in Patients With Seizure Onset Within the First Year of Life

Area of Science:

• Genetics
• Neurology
• Pediatrics

Background:

• Infantile onset epilepsy (IOE) presents significant diagnostic challenges.
• Identifying the genetic underpinnings of IOE is critical for targeted treatment and prognosis.
• A substantial portion of IOE cases remain undiagnosed with standard etiological investigations.

Purpose of the Study:

• To assess the diagnostic yield of epilepsy gene panel testing in infants with seizure onset within the first year of life.
• To determine the effectiveness of genetic testing in identifying pathogenic variants in unexplained infantile epilepsy.

Main Methods:

• Deep targeted sequencing was employed using custom capture probes.
• Analysis included germline and mosaic sequence variants, as well as copy number variations (CNVs).
• 112 patients with seizure onset before 12 months and no known etiology were studied.

Main Results:

• Pathogenic or likely pathogenic variants were identified in 47.3% (53/112) of patients.
• This included five pathogenic copy number variations (CNVs) and two validated mosaic variants.
• Diagnostic rates were higher for neonatal (61.5%) and early infantile (50.0%) onset compared to late infantile onset (28.5%).

Conclusions:

• Epilepsy gene panel testing is a valuable tool, identifying genetic causes in nearly half of infantile epilepsy patients.
• Given the expanding phenotypic spectrum and diagnostic difficulties, infantile epilepsy patients should be prioritized for genetic panel testing.
• This approach aids in understanding the genetic basis of epilepsy and improving patient management.