Emerging Role of Genetic Testing in Diagnosis of Early-Life Epilepsies

Approximately 2 in 1000 children develop epilepsy in the first three years of life. However, the cause for these seizures remains unknown in half or more cases. Currently the method used to diagnose first presentation of seizures in neonates includes microarray and neuro-imaging to name a few. A study published in JAMA Pediatrics supports the use of genetic testing, especially sequencing as a first-line diagnostic method for early-life epilepsies. What is epilepsy?

Epilepsy is a central nervous system disorder characterized by unprovoked and recurrent seizures. Seizures are a result of sudden rush of brain activity. Seizures affect the way one acts or behaves for a short period of time. Epilepsy affects all age groups but is more common in young children and older adults. Treatment with the right medications can control seizures for around 80% of people with epilepsy.

Symptoms:

• Temporary confusion
• A staring spell
• Uncontrollable jerking movements of the arms and legs
• Loss of consciousness or awareness

Genetic testing of early-life epilepsies:

The study was conducted by analyzing the results of 775 children with seizure onset before their third birthday. Participants were treated at 17 centers in the U.S. that are in the Pediatric Epilepsy Research Consortium. Neonates who had unprovoked seizures and not an immediate response to stimulus were also included.

Early-life epilepsies are often a consequence of numerous neuro-developmental disorders, most of which are proving to have genetic origins. This makes genetic testing crucial in diagnosis. Genetic testing involves reading the DNA of the patient to determine cause of the disease. There are many types of genetic testing and the effectiveness varies.

• Karyotyping: Reads only large deletions or additions in the genome.
• Micoarray: Used to determine expression levels of a gene and thereby relate it to whether the gene is functional or not.
• Epileptic gene panel: This tests for alterations in already known epilepsy related genes. However, if the cause is somewhere else, these may be missed.
• Whole Genome Sequencing: This reads the entire DNA sequence letter by letter and shows even minute alterations in the DNA. However, the test is expensive.

The study suggests that the genetic test called microarray, which is commonly used in evaluating seizures, has a lower diagnostic yield than the sequencing and panel tests. The whole genome sequencing test gives precise genetic changes in the DNA which may be used in disease diagnosis. The authors claim that identifying the precise cause for a child’s epilepsy sooner will help design effective treatment to control seizures early on. Controlling these seizures early in children is crucial to healthier brain development. The study has found that the genetic sequencing tests have very high diagnostic yield and would make other tests unnecessary.

The current study also showed that -

• Genetic testing provided a diagnosis in 25% of the children whose cause would have otherwise remained unsolved.
• Specific genetic factors were found to be the cause in 40% of patients with the fist presentation of seizure.

For children with unexplained etiology, the diagnostic yield of microarray was much lower than the sequencing based tests like the whole genome sequencing and panel tests. The study suggests that the sequencing tests may be a more efficient diagnostic strategy for children with normal brain imaging.

Concluding with the words of the corresponding author, Anne T Berg, she said "Precision medicine means nothing without precision diagnosis, and we can now provide precision diagnosis. Genetic testing should be incorporated into the routine initial evaluation of young children with epilepsy."

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References:

1. Overview - Epilepsy - (http://www.mayoclinic.org/diseases-conditions/epilepsy/home/ovc-20117206)
2. Berg, A. T., Coryell, J., Saneto, R. P., Grinspan, Z. M., Alexander, J. J., Kekis, M., . . . Koh, S. (2017). Early-Life Epilepsies and the Emerging Role of Genetic Testing. JAMA Pediatrics. doi:10.1001/jamapediatrics.2017.1743

Source-Medindia