new theory about causes of epilepsy and possible insights into apraxia

[Guest guest]

Public release date: 28-Jan-2009

Contact: Karin Eskenazi

ket2116@...

212-342-0508

Columbia University Medical Center

First gene discovered for most common form of epilepsy

Finding supports new theory about causes of epilepsy and offers

possible insights into the cause of speech dyspraxia, ADHD, DCD and

other cognitive and behavioral disorders

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.

" 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 & Surgeons and

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.