New study in pediatric epilepsy supports the value of early genetic testing as a tool for making an accurate and an early diagnosis in children

September 13, 2021

Delayed diagnosis and prolonged clinical investigations can lead to the delay in treatment and the worsening of a patient’s condition. A significant number of children with childhood-onset epilepsy have a genetic cause that can impact treatment or allows them to be part of a clinical trial for new potential treatment interventions. To maximize diagnostic yield in genetic testing, high-resolution copy number variant (CNV) detection can be a significant contributor: 25% of the diagnoses include a clinically significant CNV. A CNV is when a number of copies of a particular gene varies from normal. Many have no impact on health but some can be associated with genetic disease.

A study, recently published in PLOS ONE, evaluated the clinical utility and diagnostic yield of next-generation sequencing (NGS)–based genetic testing in children who had their first unprovoked seizure between 2 and 5 years representing one of the first studies in this age group. The diagnostic yield was over 20%, supporting the clinical utility of comprehensive genetic testing for children with seizure onset after 2 years of age.

“Studies addressing the clinical utility of genetic diagnostics for patients with seizure onset in this age group have been lacking. This study provided valuable information to support the clinical utility of genetic testing in children with seizure onset between 2 and 5 years of age, with a strikingly high diagnostic yield that was powered by high-performing NGS technology and bioinformatics,” says Blueprint Genetics Executive Medical Director Dr Tero-Pekka Alastalo.

Epilepsy is one of the most common childhood-onset neurological conditions with a genetic basis. The spectrum of epilepsies can vary from self-limited and treatable to severe, progressive and drug-resistant forms.

“Early molecular diagnosis can have a significant impact on children presenting with epilepsy, and can lead to favorable outcomes when diagnosed and treated early. Given the complexity of the disease spectrum in epilepsies and limited access to comprehensive genetic testing, it is not surprising that patients often experience delay before a genetic diagnosis is established and the underlying etiology is understood,” Alastalo continues.

A comprehensive genetic testing strategy requires a high-performing NGS platform that includes CNVs and known disease-causing noncoding variants. In this cohort, the identified CNVs ranged in size from a 242bp intragenic deletion to a 9Mb deletion affecting a number of genes, with small intragenic deletions representing 27.2% of all CNVs. This means that high-resolution CNV detection is fundamental in testing for these conditions.

Results in short:

  • The cohort included 211 consecutive patients referred for genetic testing between 2018 and 2019
  • The overall diagnostic yield was 20.4%
  • Copy number variant (CNV) analysis was performed for all patients
  • In the diagnosed cohort, 25.6% of patients were identified to have a disease-causing CNV
  • At least 63% of patients with genetic diagnosis were diagnosed with a disorder for which there is targeted treatment, evidence for optimizing pharmaceutical treatment, or ongoing clinical trials available
  • The patient cohort is part of the BioMarin Pharmaceutical Inc. sponsored testing program Beyond Paediatric Epilepsy tested between 2018 and 2019. Individuals have been consented for research as part of the programme to improve the understanding, diagnostics, and treatment of similar clinical conditions

With next-generation sequencing, genetic testing can now be considered a true diagnostic tool available to the clinician in his or her armamentarium that can be readily utilized early on as part of the diagnostic process.


Full study:

Gall K, Izzo E, Seppälä E, Alakurtti K, Koskinen L, Saarinen I, Singh A, Myllykangas S, Koskenvuo J, and Alastalo1 T. (2021) Next-generation sequencing in childhood-onset epilepsies: diagnostic yield and impact on neuronal ceroid lipofuscinosis type 2 (CLN2) disease diagnosis. PLoS ONE 16(9): e0255933.


Further information:

Saara Salonoja, Communication Specialist,

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