Genetic Testing in Early-Life Epilepsies

Study Overview

A recent study published in JAMA Pediatrics advocates for the use of genetic testing, particularly DNA sequencing, as a primary diagnostic approach for children under three years old who experience epilepsy and seizures.

Challenges in Seizure Management

Epilepsy, a disorder of the nervous system, is defined by unprovoked and recurrent seizures. While it can affect individuals of any age, it is particularly prevalent among young children. Approximately 80% of people with epilepsy can manage their seizures effectively through medication. However, treating children under three presents unique challenges, as early-life epilepsies often stem from a variety of neuro-developmental disorders with genetic roots. Compounding the difficulty is the fact that the underlying causes of seizures in this age group often remain unidentified.

Identifying the Cause of Seizures

Rapid identification of the specific cause of a child’s epilepsy is essential for healthcare providers to select the most effective treatment strategies, ultimately supporting healthy brain development. Typically, young patients presenting with seizures undergo neuroimaging as part of their initial diagnostic evaluation. Genetic testing, which analyzes a patient’s DNA for disease-related changes, is becoming an increasingly viable option. Various genetic tests available include:

– Karyotyping to analyze the structure and number of chromosomes.
– Microarray analysis to assess gene expression levels.
– Epileptic gene panels that sequence genes to identify alterations in known epilepsy-related genes.
– Whole genome sequencing that examines the complete DNA sequence.

Results of the Diagnostic Testing

Researchers led by Dr. Anne Berg examined medical records of 775 children (408 males and 367 females, with a median age of seizure onset at 7.5 months) to evaluate the utilization and diagnostic effectiveness of genetic tests for early-life epilepsies. Among these, 725 children underwent neuroimaging, with 80% receiving epilepsy protocol magnetic resonance imaging. However, only 38% of these imaging tests resulted in a specific diagnosis or indicated a developmental or progressive brain disorder.

Genetic testing yielded the following results:

– Karyotyping confirmed genetic diagnoses in 44 children (including conditions such as trisomy and other chromosomal abnormalities).
– Chromosomal microarrays were performed for 188 children.
– Gene panels were conducted for 114 children, while 43 received whole exome sequencing.

The study revealed that whole genome sequencing and epileptic gene panels provided diagnoses in 33% and 27% of cases, respectively, while microarray and karyotyping offered a diagnosis in only 17% of instances. Notably, specific genetic factors were identified as the cause of seizures in 40% of the patients. Additionally, genetic testing diagnosed 25% of children whose seizure causes would have otherwise remained unknown.

Limitations of Genetic Testing

Despite its findings, the study published in JAMA Pediatrics has limitations. It was not population-based, and the data were derived from medical records, leading to inconsistencies in testing and result availability. Nevertheless, the authors emphasize that not all genetic tests yield the same effectiveness. They advocate for routine genetic testing to be included in the initial evaluation of seizures in young children. This genetic information can also assist in treatment decisions, helping physicians determine whether specific drugs may exacerbate or alleviate seizures based on the underlying cause of epilepsy.

Reference

Berg AT, Coryell J, Saneto RP, et al. Early-life epilepsies and the emerging role of genetic testing. JAMA Pediatr. 2017;171(9):863-871. doi:10.1001/jamapediatrics.2017.1743