Epilepsy Genetics Program

Frequently asked questions: Genetics of Epilepsy and Related Neurological Disorders

What is the Goal of Epilepsy Genetics Research?

Many children with epilepsy experience seizures which respond well to treatment. A few types of epilepsy, however, are characterized by seizures which begin very early in childhood and are associated with severe intellectual and/or developmental disabilities. These conditions, known as progressive epileptic encephalopathies, are particularly severe and are often difficult to treat. These syndromes include infantile spasms, early infantile epileptic encephalopathy with suppression bursts (Ohtahara syndrome), malignant migrating partial epilepsy of infancy, early myoclonic epileptic encephalopathy, and severe myoclonic epilepsy of infancy (Dravet syndrome).

Our current research effort is focused on children with epileptic encephalopathies, in particular Ohtahara syndrome.  Our goal is to identify genetic alterations (known as “mutations”) that cause Ohtahara syndrome. By doing so we hope to improve diagnosis and treatment for this condition. It is also possible that understanding the genetic basis of Ohtahara syndrome may in some instances make it possible to prevent it from occurring in the future.

What is Ohtahara Syndrome?

Ohtahara syndrome is a type of epileptic encephalopathy which was first described in 1976 by Shunsuke Ohtahara, a Japanese child neurologist. The syndrome is characterized by specific types of seizures, such as tonic spasms and partial seizures, and by a characteristic EEG finding known as burst suppression. Most children with Ohtahara syndrome begin having seizures within the first three months of life, though the seizures may not be recognized by parents or caregivers immediately. Seizures become more frequent, and some children with Ohtahara may not survive infancy.  Developmental delays in young children are common, as are physical and intellectual disabilities as children get older. Some children with Ohtahara syndrome may later develop other epilepsy syndromes, such as West syndrome or Lennox-Gastaut syndrome. Ohtahara syndrome is estimated to occur in about 0.2% (2 in 1000) of childhood epilepsies.

What Causes Ohtahara Syndrome?

There is no single cause for Ohtahara syndrome, though often it is due to structural brain abnormalities and/or underlying metabolic disorders.  Genetic factors play an important role in causing Ohtahara syndrome and to date mutations have been identified in a small number of genes. Most frequently, mutations are identified in either the STXBP1 gene or the ARX gene (the latter particularly in boys). This testing is clinically available through several laboratories in the United States and elsewhere. However, in the majority of children with Ohtahara syndrome, currently available genetic testing will not lead to the identification of a specific genetic cause. For most children with Ohtahara syndrome, we still do not know the underlying genetic cause of their condition. Therefore, continued research is needed to identify additional genes that play a role in Ohtahara syndrome.

Who Can Participate in Epilepsy Genetics Research?

If your child has been diagnosed with Ohtahara syndrome, your family may be eligible to participate in Boston Children Hospital’s Genetics of Epilepsy and Related Neurological Disorders research protocol. Your family does not need to live in the Boston area to participate.

What Does Participation Involve?

Your family does not need to travel to Boston Children’s Hospital to participate in this research study. In order to participate, your child must provide a blood sample (or other source of DNA). Ideally, we also collect blood/DNA samples from both biological parents and in some instances siblings.  In addition, we will conduct a detailed interview (either by phone or in person) to collect family and medical history. This interview will last approximately 1 hour. We will also review your child’s medical records, including EEG data and any imaging studies (such as MRI) performed in the past, in order to get a complete overview of your child’s medical history.

Will I Learn the Results of the Research?

Through our research we hope to identify gene mutations that lead to Ohtahara syndrome.  In order to do this we need DNA samples from many children with Ohtahara syndrome, as well as their immediate family members.  Rather than looking at specific genes already known to play a role in Ohtahara syndrome, we will be performing exome sequencing, a technique which enables us to examine all 20,000 genes in the entire human genome.  If we identify genetic information that is relevant to your child’s epilepsy diagnosis, we will notify you and you will have the opportunity to learn the results.  It is important to note, however, that research takes considerable time and it may be months or even years before we have any information that could be clinically useful to individuals or families. 

If I Have More Questions, or Would Like to Participate, Who Can I Contact?

If you would like to participate in this study, or if you have questions about participation, you can reach the Epilepsy Genetics program by email at: EpilepsyGenetics@Childrens.Harvard.edu

We look forward to hearing from you!