- Epilepsy is a
nervous system disorder characterized by repeated seizures.
- Genetic factors
played a role in 40% of patients with first presentation of seizure.
- Whole genome
sequencing and panel testing yield more data for diagnosing early-life
epilepsy when compared to microarray and karyotyping.
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
What is 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.
‘Whole genome sequencing and epilepsy panel sequencing have higher diagnostic yield when compared to frequently used microarray in early life epilepsies.’
Genetic testing of early-life epilepsies:
- A staring spell
jerking movements of the arms and legs
- Loss of
consciousness or awareness
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.
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.
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."
- Overview - Epilepsy - (http://www.mayoclinic.org/diseases-conditions/epilepsy/home/ovc-20117206)
- 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