Projects

GENE DISCOVERY PROJECT

This is an international search on the World Wide Web for families with epilepsy in order to:

More information can be found at: http://www.epilepsyfoundation.org/gdp/.

It starts with a simple blood test. Basically, DNA from family members who have seizures is compared with the DNA from those who do not.

A blood sample from each person in the family is usually required, but even a small family can often provide a great deal of information.

It is not possible yet to detect all epilepsy genes. In some families, there are too few members with seizures to complete the analysis; in others, the gene is linked to a region of the chromosome where the map is not yet complete.

Some day, many epilepsy genes will be known, and that will speed detection in most families. This project can help us reach that goal.

GENETICS OF EPILEPSY

t is now clear that most inherited epilepsies are benign and easily treated, and that the risk of having affected children is low. In an individual or family, accurate identification of the type of epilepsy syndrome now allows precise genetic counselling to be offered. Major molecular genetic advances can be realistically expected in the next five years. These are likely to change our concepts regarding the mechanisms of the epilepsies, will probably provide new avenues for therapy and perhaps even suggest strategies for prevention.

Understanding the causes of epilepsy is fundamental to improving treatment. An inherited component has been recognized since the time of Hippocrates, but the genetics have been poorly understood. Unfortunately, the fact that epilepsy may be inherited has added to inappropriate prejudice against people with epilepsy.

Until recently, progress was slow in this field and few researchers were working on the genetics of epilepsies. But there have been significant advances in the last few years. Two major developments sparked great interest in epilepsy genetics. First, the clinical recognition that there are many identifiable epilepsy syndromes, some of which are inherited, and that there are genetic distinctions between them. Second, the revolution in molecular biology now allows researchers to identify the location and nature of genes that cause epilepsies. The promise is that identification of these genes will allow deep understanding of the mechanisms of different forms of epilepsy and provide new insights into rational approaches to treatment.

Clinical research has resulted in the identification of a number of specific inherited epilepsies. Two of the syndromes to be recognized so far are benign infantile familial convulsions, and autosomal dominant nocturnal frontal lobe epilepsy. The former begins at about six months of age and is associated with clusters of partial and secondarily generalized seizures. The family history may not be apparent unless carefully searched for. It is clinically and genetically distinct from the syndrome of benign neonatal familial convulsions, which characteristically begins around five days after birth. The importance of recognizing this syndrome is that it has a uniformly excellent outcome, so parents can now be counselled that their child will not have ongoing seizures.

Autosomal dominant nocturnal frontal lobe epilepsy is a syndrome where motor seizures with tonic or hyperkinetic features occur exclusively at night. This disorder was frequently misdiagnosed as a variety of conditions including night terrors, other sleep disorders, or hysteria. Treatment with carbamazepine is usually highly effective.

Family studies of the more common epilepsies such as juvenile myoclonic epilepsy and absence epilepsies have resulted in better understanding of the complexities of their genetics. It now seems likely that these epilepsies, like certain other common disorders with an inherited component, such as diabetes and hypertension, are caused by more than one gene. Special strategies now being developed will be needed to solve the molecular genetic problems posed by these genetically complex disorders.