About My Health Careers Internship MedBlogs Contact us
Medindia LOGIN REGISTER
Advertisement

Mutations that cause Severe Infant Epilepsy Identified

by Hannah Joy on March 21, 2018 at 4:05 PM
Font : A-A+

Mutations that cause Severe Infant Epilepsy Identified

A missing mutation in severe infant epilepsy has been identified that triggers brain-damaging electrical signaling leading to seizures.

Scientists also found early indications that specific anti-seizure medications might prevent disabling brain injury by controlling epilepsy during a crucial period shortly after birth.

Advertisement


"These are still early days, but we may be able to use this knowledge to protect the newborn brain and improve a child's long-term outcome," said study leader Ethan M. Goldberg, MD, PhD, a pediatric neurologist at Children's Hospital of Philadelphia.

Goldberg collaborated with European and American researchers in this neurogenetic study of early infantile epileptic encephalopathy, published online in Annals of Neurology.
Advertisement

The study focused on mutations in the gene SCN3A. Scientists already knew that the gene had a pattern of high expression in the brain, before and shortly after birth.

Variants in SCN3A had also been previously linked to less severe forms of epilepsy but the current research solidified this link and was the first to establish that SCN3A mutations cause the severe infantile form.

The gene regulates sodium channels that allow sodium ions into brain cells: "sodium influx underlies action potentials, which are the currency of information transfer in the brain," said Goldberg. Of four sodium ion channels predominantly expressed in the brain, he added, scientists had discovered that gene mutations in three of those channels already had a clear role in causing forms of epilepsy. Only one channel, called Nav1.3, encoded by the SCN3A gene, had not previously been linked to epilepsy, and hence was the "missing channel."

The new research implicated novel SCN3A mutations in severe childhood epilepsy, joining the other brain-expressed sodium channels as causes of early infantile epileptic encephalopathy.

"We identified gain-of-function mutations in SCN3A," said Goldberg. "These mutations generate increased channel activity that leaves the ion channel stuck open and leaking current. This overactivity, in turn, leads to epileptic encephalopathy, the most severe type of childhood epilepsy."

The study team reported on a cohort of four unrelated children from different countries, all of whom had severe epilepsy. Their epilepsy had a particularly early onset, within the first two weeks of life. For the children, the results were devastating: severe to profound developmental delay, seizures that did not respond to medication and lifelong disability.

The researchers used whole-exome sequencing to pinpoint mutations in SCN3A. The mutations were de novo--present in the affected children, but not inherited from the parents.

Cell studies, including electrophysiological recordings, revealed detailed properties of the electrical signaling.

Further cell culture studies also showed that existing anti-seizure medications, lacosamide and phenytoin, selectively inhibited the persistent current in mutant ion channels--suggesting a possible future therapy for this condition.

Translating these findings into potential clinical treatments, Goldberg stressed, will require considerable further research--both in nerve cells and in future animal models, in which neurologists can test possible precision-medicine treatments for safety and efficacy before they can be investigated in patients.

In addition, the current research allowed the SCN3A gene to be added to an existing diagnostic test, CHOP's Epilepsy Panel, which uses next-generation sequencing to rapidly test for over 100 genetic causes of childhood epilepsy.

Precise, early diagnosis, added Goldberg, will be crucial, because of the highly regulated timetable of early-life neurological events.

"The mutation's activity in the Nav1.3 sodium ion channel occurs during a short period in newborns, but if we can intervene during that window, we may be able to help prevent long-term neurological injury and benefit patients," he said.



Source: Eurekalert
Advertisement

Advertisement
News A-Z
A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
News Category
What's New on Medindia
Health Benefits of Giloy
Breast Cancer Awareness Month 2021 - It's time to RISE
First-Ever Successful Pig-To-Human Kidney Transplantation
View all

Medindia Newsletters Subscribe to our Free Newsletters!
Terms & Conditions and Privacy Policy.

More News on:
Epilepsy Febrile Fits / Febrile Convulsions Reye’s Syndrome McArdle Disease Convulsions Electroencephalogram Aicardi-Goutieres Syndrome Cavernous Malformation Dravet Syndrome Absence Seizure 

Recommended Reading
Cooling Treatment can Reduce Chances of Epilepsy in Kids
Therapeutic cooling treatment in babies deprived of oxygen at birth (birth asphyxia) can help ......
New Targets for Epilepsy Treatment can be Identified
New analysis shows underlying biology of genes that cause infantile spasms. This helps in the ......
Epilepsy Drug Levetiracetam may be Better Than Phenobarbital
Most commonly prescribed drug for infantile epilepsy Levetiracetam, may also be more effective than ...
Wristband Devices Improve Detection in Patients With Epilepsy
The new wristband devices developed can monitor dangerous seizures in patients with epilepsy, ......
Absence Seizure
Absence seizure (petit mal epilepsy) involves sudden lapse in consciousness and staring blankly into...
Aicardi-Goutieres Syndrome
Aicardi-Goutieres Syndrome is observed in infants and older children. To date, defects in 6 genes ar...
Cavernous Malformation
Cavernous malformations are malformations in blood vessels that can cause neurological disorders whe...
Convulsions
Seizure or a convulsion is a result of abnormal electrical activity in the brain. If there are two o...
Dravet Syndrome
The result of a rare genetic mutation, Dravet syndrome is an unusual case of epilepsy in children....
Electroencephalogram
An electroencephalogram (EEG) detects electrical activity in the brain using electrodes attached to ...
Epilepsy
Fits or convulsions or Epilepsy is characterized by recurrent, involuntary seizures and is described...
Febrile Fits / Febrile Convulsions
High fever in kids can cause convulsions and are called febrile fits that do not include the seizure...
McArdle Disease
McArdle disease is a genetic disorder in which the body cannot breakdown glycogen in the muscles. It...
Reye’s Syndrome
Reye's syndrome is a medical emergency chiefly affecting children and teenagers and is marked by the...

Disclaimer - All information and content on this site are for information and educational purposes only. The information should not be used for either diagnosis or treatment or both for any health related problem or disease. Always seek the advice of a qualified physician for medical diagnosis and treatment. Full Disclaimer

© All Rights Reserved 1997 - 2021

This site uses cookies to deliver our services. By using our site, you acknowledge that you have read and understand our Cookie Policy, Privacy Policy, and our Terms of Use