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Volume 09
Journal of Alzheimers Disease & Parkinsonism
ISSN: 2161-0460
Epilepsy 2019
Parkinsons Congress 2019
August 29-31, 2019
JOINT EVENT
conferenceseries
.com
August 29-31, 2019 Vienna, Austria
&
5
th
International Conference on
Epilepsy & Treatment
5
th
World Congress on
Parkinsons & Huntington Disease
The importance of genetic testing in pediatric epilepsy
Stephen Nelson
Tulane University School of Medicine, USA
Background and Objective:
Epilepsy is a very common medical problem worldwide, affecting 0.5-1 percent of
the population. Although there can be multiple etiologies for seizures, such as brain malformations or traumatic
brain injury, it is increasingly recognized that genetics plays an important role in epilepsy. Testing options include
chromosomal microarrays, epilepsy panels, and whole Exome sequencing. Genetic causes of epilepsy are many,
but include mutations in ion transporters or channels, neurotransmitter receptors, metabolic disorders, and many
others. The discovery of a genetic etiology can have profound impacts on treatment decisions, recurrence risk,
and prognosis, and thus testing should be considered in all patients with an otherwise unexplained cause for their
seizures.
Study Design:
More than 100 patients with epilepsy were tested by a combination of chromosomal microarrays,
epilepsy panels, and whole Exome sequencing as part of their evaluation for recurrent seizures. Additionally, MRI
imaging and EEGs were done, to correlate with seizures and genetic test results. Some patients underwent Vagus
Nerve Stimulation (VNS) placement for refractory seizures with demonstrated benefit above medical therapy alone.
Study Participants and Settings:
All patients were between the ages of newborn to 30 years old and seen as inpatients
or outpatients through Tulane University School of Medicine.
Materials and Methods:
Samples were collected from > 100 patients with a variety of epilepsy types, and sent for
chromosomal microarray, epilepsy panels, or whole Exome sequencing, depending on the clinical indications. Some
patients with negative microarrays and epilepsy panels were reflexed to whole Exome, to determine if that increased
the yield of detecting abnormalities.
Results:
Avariety of pathogenicmutations were found, some of which had tremendous impact on treatment decisions.
Chromosomal duplications and deletions detected by chromosomal microarray can be rapidly tested for at low cost,
but had a lower yield than epilepsy panels, where genes suspected to be involved with epilepsy are fully sequenced.
Whole Exome sequencing or mitochondrial DNA testing rarely added additional information regarding etiology in
patients without other neurological signs and symptoms such as autism or developmental delay. Additionally, VNS
implantation demonstrated benefit even in young children and those with generalized seizures, with both reductions
in seizures and improvements in behavior and development.
Conclusion:
Epilepsy panels were very high yield, followed by chromosomal microarrays and whole Exome
sequencing. Important examples include avoiding sodium channel blocking antiepileptic medications in patients
with sodium channel mutations, treatment by Ketogenic diet in patients with CSF glucose transporter mutations,
etc. Furthermore, the fact that some patients with genetic mutations associated with severe epilepsy phenotypes
that were refractory to multidrug therapy were responsive to VNS suggests this should be an early consideration in
patients with genetic epilepsies. Early genetic testing can have significant impacts on treatment decisions, and thus
should be strongly considered in patients with epilepsy, especially those that are refractory to medications or who
have comorbid conditions such as autism or developmental delay.
J Alzheimers Dis Parkinsonism 2019, Volume 09