First Gene Discovered For Most Common Form Of Epilepsy

[Birdbomb]

First Gene Discovered For Most Common Form Of Epilepsy

NEW YORK (January 28, 2009) — An international team of researchers, led by investigators at Columbia University Medical Center, has uncovered the first gene linked to the most common type of epilepsy, called Rolandic epilepsy. One out of every five children with epilepsy is diagnosed with this form, which is associated with seizures starting in one part of the brain.

Results of the study were published in an advance online issue of the European Journal of Human Genetics on January 28, 2009.

The finding is the first step in unlocking the causes of common childhood epilepsies and developing more effective treatments. Children with Rolandic and other types of epilepsies are usually treated with drugs that prevent seizures by suppressing electrical activity in the entire brain.

The researchers searched the entire genome of 38 families and found a single region on chromosome 11 that was linked to the EEG pattern seen in Rolandic epilepsy. Then by comparing markers in 68 patients and 187 controls across all the genes in this region, they narrowed down the association to markers within the ELP4 gene, shown as the largest red triangular block above.

"Epilepsy medications are effective for many children but there is concern that some of the cognitive and behavioral problems that children with epilepsy often suffer might be attributable in part to these drugs," says the study’s senior author, pediatric neurologist Deb Pal, M.D., Ph.D., Columbia University research scientist in the Department of Psychiatry at the College of Physicians and Surgeons and in the Division of Statistical Genetics at the Mailman School of Public Health and in the Division of Epidemiology at the New York State Psychiatric Institute. "Most epilepsies have a genetic influence, much of which has yet to be discovered. If we knew the actual genetic causes, then we could try to stop or reverse the processes that lead to seizures and other neurological impairments. This finding will hopefully help lead us to the right intervention."

In the study, the researchers searched the entire genome of 38 families and found a region on chromosome 11 that was linked with Rolandic epilepsy. Then, by comparing this region in people with Rolandic epilepsy to unaffected controls (255 people in total), the researchers pinpointed the gene, called ELP4.

The finding was replicated in a completely different set of patients and controls collected by the team’s Canadian members, with the same result. Though Dr. Pal says an outside group still needs to replicate the findings, the two independent experiments provide strong evidence that ELP4 is truly linked to Rolandic epilepsy.

ELP4 has never before been linked to a human disease but is related to a group of genes (transcriptional regulators) that recently have been associated with other common forms of epilepsy. All these genes appear to influence the organization of brain circuits during development.

The discovery of genes like ELP4 are slowly altering the prevailing view of the cause of common epilepsies. Instead of stemming from changes in the brain’s ion channels, as previously thought, the disorders likely stem from the way the brain’s neurons connect to each other during development, researchers now believe.

With that perspective, it is not surprising that children with epilepsy often have other learning and behavior problems. "We shouldn’t think of epilepsy as just about the seizures, but also about all the other brain impairments we see, like a delay in speaking, reading difficulties, and attention problems," Dr. Pal says. "Seizures are one, but not the only, consequence of these children’s slightly altered brain development."

The findings also offer possible insights into the causes of attention deficit hyperactivity disorder (ADHD), speech dyspraxia (a speech disorder in which a person has a delay in speech development due to motor coordination difficulties), and developmental coordination disorder (DCD). Children with these developmental disorders often have the same spiky brainwave pattern that is present in children with Rolandic epilepsy. Understanding how the ELP4 gene is related to the brainwave pattern may help researchers uncover the causes of these disorders.

Rolandic epilepsy, named for the region of the brain affected by the seizures, begins almost exclusively in children between the ages of 3 and 12. Seizures typically start in the morning just after the child wakes up and cause a loss of muscle tone in the face and a loss of speech. Seizures stop on their own after several minutes. Most children grow out of the disorder by adolescence.

Additional authors of this study include David A. Greenberg, Ph.D., director, Division of Statistical Genetics and professor of the Department of Biostatistics at the Mailman School of Public Health and The New York State Psychiatric Institute and Lisa Strug, Ph.D., formerly an assistant professor Columbia University Mailman School of Public Health’s Department of Biostatistics, Division of Statistical Genetics.

The study was supported by members of the Partnership for Pediatric Epilepsy Research (American Epilepsy Society, Epilepsy Foundation, Anna and Jim Fantaci, Fight Against Childhood Epilepsy and Seizures, Neurotherapy Ventures Charitable Research Fund, Parents Against Childhood Epilepsy); Epilepsy Foundation, through the generous support of the Charles L. Shor Foundation for Epilepsy Research, Inc.; and the NIH.

http://www.cumc.columbia.edu/news/press_releases/090128_RolandicEpilepsy.html

 

[brain]

Whoo Hoo! I can forward this post to a close dear
friend of mine who on earth has no clue why her
last child has Rolandic! She had been using me for
all sorts of information and a shoulder to lean on!

I'm gonna toss her over here!

 

[Bernard]

The discovery of genes like ELP4 are slowly altering the prevailing view of the cause of common epilepsies. Instead of stemming from changes in the brain’s ion channels, as previously thought, the disorders likely stem from the way the brain’s neurons connect to each other during development, researchers now believe.

Amazing. Guess what happens with neurofeedback? The brain grows new connections between the neurons as it learns to operate in a more optimal (normalized) manner.

 

[joan]

I was told in 2008, that within 5 years, they would know the gene involved with JME and start to understand if its the same for all JMEs. That my Grandchildren would be born non JME. Progress is coming. Slowly but surely. From their lips to Gods ear**

joan*

 

[Porchlight]

Has anyone tried to find out whether they have the markers on the ELP4 (Ch11) gene by uploading their raw information from 23andme, AncestryDNA, and Family Tree DNA onto GEDmatch and using the GEDmatch tools?

If so, please tell me how you did it. We have raw sequencing for our son, but I really don't understand how to use the GEDmatch tools. If he has these markers, I would really love to be able to bring the information to his epileptologist.

 

[seagull]

I have e my daughter also Bernard describe it perfectly but I also had fracture skull e started then daughter had meningitis e started then.i don't think I will ever know.maybe our threshold was low and brain accidents kicked it into action.my daughter e stopped as adolescent but if eeg or scan is done it still show abnormal but as it not effecting her putting her onto medication counter productive