THE EPILEPSY GENE
by Hoda Ossoble
A few months ago, patient X, who has had epilepsy her whole life, went into her doctor's office with a worried look on her face. Already five months pregnant, she said "Doctor, All I really want to know is……. will my child have seizures?" Although science is playing a major role in helping us to clarify whether or not genes affect epilepsy, the answer patient X was seeking, cannot be summed up in a simple "yes" or "no". In this article I will examine the complex process of heredity as well as the more recent findings on genes which relate to epilepsy.
Genes are the basic units or building blocks of inheritance. Humans have over 100 000 genes, and each gene influences a specific trait, for example: hair color, eye color, and blood type. Chromosomes are structures which are composed of DNA. Humans have 23 pairs of chromosomes, half are provided by the mother and half by the father. The genes positioned on a chromosome are arranged in a precise sequence, where each specific gene is placed in the same location, this occurs in all individuals. If the sequence were to become altered then that could result in a disease, which may later be passed on to the offspring. (1)
Some characteristics are inherited through single genes, either from your mother or your father. There are several patterns of single gene inheritance; for example sex-linked inheritance, referring to the 2 chromosomes that determine one's sex (XX for females, XY for males). Sex chromosomes make up 2 of an individual's 46 chromosomes. If the abnormal gene is located on the X chromosome, then it is X-linked. If epilepsy were to be an X-linked dominant trait, because of the term dominant (meaning that it overrides the other genes' genetic information), only one copy is needed to spread the disorder on to the offspring. In this case all who possess the dominant gene are affected with the disorder. If epilepsy was an X-linked recessive trait, (meaning the gene is often not expressed in the individual), males would be affected more because they only carry one X chromosome from their mother. For females the only way for the recessive trait to be expressed is if a second X-linked recessive gene is present. Since it is more likely that someone will inherit one copy rather than two of the abnormal gene, X-linked disorders are much more common in males than in females. Most cases of epilepsy are not caused by single gene inheritance, although a few rare cases of epilepsy are results of a single altered gene, and through studying them we have been able to closely examine the genetic complexity of epilepsy. (2)
To figure out whether or not epilepsy can be inherited is complicated for many reasons. There are many other factors that may influence whether or not the abnormal gene will cause the disorder. Sometimes inheritance of a specific gene is not enough to cause a disorder on its own, in this case environmental factors work together to cause it. This phenomenon is known as gene-environment interaction. These genes work together to increase the risk of developing epilepsy. Even when two individuals may appear to have the same type of epilepsy or epilepsy syndrome, they may have the syndrome for different reasons. For instance, two brothers may both have epilepsy with generalized tonic-clonic seizures, one as a result of a genetic cause, and the other as a result of head trauma. This is called etiologic heterogeneity, meaning the seizures are a result of different causes. (3) Since the relationship between genes and the development of seizures is so complex, instead of saying epilepsy is inherited, it is more accurate to say that the risk of epilepsy is probably influenced by genes.
The threat that hereditary inheritance poses to family members depends on the type of epilepsy the individual has. In the close relatives (parents, brothers, sisters and children) of patients with generalized epilepsy, the risk of epilepsy is higher than in the close relatives of people with partial or focal epilepsy. Absence epilepsy seems to have a particularly strong genetic influence. Several studies have shown that the risk to relatives of patients with absence seizures is higher than for other generalized or partial seizure types. But the effect of genetic factors for developing epilepsy decreases, as people get older. So exactly how many genes have been discovered that influence the risk of getting epilepsy? The only genes associated with epilepsy that have been discovered to date are responsible for relatively rare forms of epilepsy. These include generalized epilepsy with febrile seizures, dominant nocturnal frontal lobe epilepsy, and partial epilepsy with auditory features, but for most forms of epilepsy the influence of genetics has yet to be determined. (4)
Back at the doctor's office patient X was reassured that the risk of her child having seizures was quite low. Her baby will most likely be born healthy, and show no signs of epilepsy or any other neurological disorder. Although genes play an important role in epilepsy, specific genes have still not yet been identified for most epilepsy related disorders. Discovering the genes that cause epilepsy can help us to understand more about the biological processes in the brain that affect the risk of seizures. These discoveries may also someday enable us to recognize people who are at risk for seizures, and start treatment early. As well, this understanding may someday lead to the development of completely new treatments and possibly even strategies to prevent epilepsy before it begins.
SOURCES:
1) Epilepsy Family Study. 06/2003. Columbia University. Available at: http://cpmcnet.columbia.edu/dept/epilepsy/
2) Inheritance of x-linked Dominant Diseases. 2000-2005. WrongDiagnosis.com Available at:http://www.wrongdiagnosis.com/genetics/xdom.htm
3) Gene Environment Interaction Fact sheet. 08/2000. Centre for Disease Control and Prevention. Available at: http://www.cdc.gov/genomics/info/factshts/geneenviro.htm
4) Epilepsy Family Study. 06/2003. Columbia University. Available at: http://cpmcnet.columbia.edu/dept/epilepsy/discoveries.htm
ADDITIONAL RESOURCES:
