Monday, December 7, 2015

Juvenile myoclonic epilepsy, CNVs and drug resistance

One in ten children with juvenile myoclonic epilepsy (JME) whose seizures don’t improve with antiepileptic drugs share specific copy number variants (CNVs) that could be used to identify treatment-resistant patients.
The finding, reported on Sunday at the annual meeting of American Epilepsy Society, could help families seek alternative strategies to address JME, a disorder characterized by seizures and cognitive and behavioral problems.
JME usually triggers involuntary muscle twitching upon waking, as well as tonic-clonic and absence seizures, in children between the ages of 12 and 18, the lead study author, Rhys Thomas, MD, PhD, a neurologist at the University Hospital of Wales and the MRC Centre for Neuropsychiatric Genetics and Genomics at Cardiff University in the United Kingdom, told the Neurology Today Conference Reporter ahead of the session. About 20 percent of patients do not respond to the standard treatment of sodium valproate, he said.

The results of the test could also help neurologists "change their expectations," said Dr. Thomas. "If you expect someone to be seizure free, you may accept a different level of drug control and not be heavy-handed with dosing. We have very few markers of how people will do on antiepileptic therapy. This is the beginning of personalized medicine for JME."... 

They identified 13 hotspot CNVs, and eight of them were confirmed with assays. There were two cases with 1q31.1 deletions. Another 14 CNVs, which were identified and confirmed in 11 patients, have been previously linked to autism, intellectual disability, or schizophrenia.

Commenting on the study, Heather C. Mefford, MD, PhD, an associate professor in the pediatrics division of genetic medicine at the University of Washington in Seattle, said: What's new about the Thomas abstract is that it seems these CNVs are enriched in patients who tend to be more resistant to current antiepileptic drugs. It may imply that people with these deletions and JME have a slightly different disorder, requiring a different therapeutic approach."

Dr. Mefford, who has studied genetic variants in adult epilepsy patients, added: "Understanding the genetic cause in individual patients is the first step to helping us differentiate patients and begin to individualize therapies.


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