OCT 21, 2018 08:35 AM PDT

The Genetic Cause of Severe Childhood Epilepsy is Revealed

WRITTEN BY: Carmen Leitch

An international team of researchers has established the cause of a hard-to-treat, severe form of epilepsy that strikes in childhood. They found that genetic mutations that occur spontaneously in a specific gene interfere with a channel that controls calcium flow. That leads to epileptic overactivity in the brain. This work, which was reported in the American Journal of Human Genetics, has opened up new therapeutic avenues for the rare disease as well.

 

"Even though variants in this gene were only just discovered to cause disease, we already have a good understanding of how changes in the gene's associated protein affect brain function - causing neural overactivity in epilepsy," said first author Katherine L. Helbig, MS, CGC, a research genetic counselor in the Neurogenetics Program in the Division of Neurology at Children's Hospital of Philadelphia (CHOP). "Furthermore, although much follow-up research remains to be done, we found that there is a possibility that specific anti-seizure medications could reduce this overactivity in some patients."

Almost one hundred scientists from several countries were involved in this study, which examined changes in a gene called CACNAIE, which has been thought to play a critical role in the control of electrical activity in neurons. This is the first time, however, that it’s been connected to epilepsy.

The researchers used next-generation sequencing to examine the genomes of 30 infants and children with childhood epilepsy. Their work revealed the variations in the CACNA1E gene sequence that were causing the disease. In the majority of cases, the mutations were not passed from parent to child, which are called de novo mutations. These are appearing in a growing number of severe childhood epilepsy cases. 

"The fact that we were able to identify 30 patients at this stage of research indicates that we could be looking at a more common cause of genetic epilepsy than we would have initially assumed," noted Helbig. “This research enables us to give some families an answer as to why their child has severe epilepsy. It also offers the potential that we can build on this knowledge to find new strategies for treatment,” she added.

The disease also causes delays in development, poor muscle tone, movement disorder, and a hardening of the muscles called contractures that begins at birth. "Many of the children were initially thought to have a severe muscular condition because of their contractures," said Helbig. "We were surprised to find that a genetic epilepsy had such severe symptoms."

A channel controls the flow of calcium in brain cells. The mutations disrupt the activation of that channel, causing it to become active too easily or be slow to inactivate, which cause epilepsy. The researchers observed that sometimes, the calcium current in the cells was off the charts.

Unfortunately, most of the patients under study were unresponsive to epilepsy treatments, although a few responded to topiramate, a drug that targets the CACNA1E channel. The team plans to follow up on those cases as well as other parts of this investigation. They are hoping to develop targeted treatments for kids with severe genetic epilepsy.


Sources: MedicalXpress, American Journal of Human Genetics

About the Author
  • Experienced research scientist and technical expert with authorships on 28 peer-reviewed publications, traveler to over 60 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
SEP 22, 2018
Videos
SEP 22, 2018
How Much of the Human Genome is Just Junk DNA?
Once written off as junk, it was suggested that some regions of the genome that don't code for protein act as regulators. But how much?...
SEP 29, 2018
Videos
SEP 29, 2018
CRISPR Technology may Have Serious Drawbacks
The CRISPR gene-editing system has been touted as a miraculous tool, but it has its problems....
OCT 16, 2018
Genetics & Genomics
OCT 16, 2018
Lab-grown Neurons Help Uncover the Genetic Changes Underlying Mental Illness
Developing therapeutics that will effectively relieve mental illness means understanding what is causing those disorders in the first place....
OCT 20, 2018
Videos
OCT 20, 2018
Understanding how the Immune System is Controlled
Scientists are trying to learn more about a gene, PTPN22, that is especially critical to the immune system....
OCT 23, 2018
Genetics & Genomics
OCT 23, 2018
Sperm Can Pass Epigenetic Information Onto Offspring
We are born with a genome that doesn't change, but small modifications can be made to that genetic material throughout our lives....
NOV 12, 2018
Cell & Molecular Biology
NOV 12, 2018
A New Look at Messenger RNA
Researchers have discovered that longstanding textbook knowledge about an important molecule called mRNA is probably incorrect....
Loading Comments...