The concept of genetic epilepsy is that the epilepsy is, as best we understand, the direct result of a known or presumed genetic defect(s) in which seizures are the core symptom of the disorder. The genetic defect may arise at a chromosomal or molecular level. It is important to emphasize that "genetic" does not mean the same as "inherited" as de novo mutations are not uncommon. Having a genetic etiology does not preclude an environmental contribution to the epilepsy.
In this section of EpilepsyDiagnosis.Org, important genetic etiologies for epilepsy that can be identified on clinical testing are presented:
A gene abnormality that is inherited from a parent at conception. The gene abnormality is therefore present in the individual's parent/s. It may be in all the parent's cells, or it may only be in a percentage, and therefore only in a percentage of their egg/sperm cells (see mosaicism below). Each gene exists with two copies. Some inherited conditions require only one of copy of the gene to be abnormal (known as autosomal dominant), other inherited conditions require both copies of the gene to be abnormal for the condition to occur (autosomal recessive).
As parental gonadal cells (the egg or sperm) are randomly allocated only one copy of the parent's two copies of each gene, the inheritance of a gene abnormality in parent egg or sperm cells can be predicted. If the mothers two copies (alleles) for a particular gene are AB, and the paternal two copies for the same gene are CD, the egg may contain only allele A or B, and the sperm only allele C or D. At conception (when one egg and sperm randomly fuse), the offspring can only have the following combinations: AC, AD, BC or BD. In this case, if gene A is abnormal, then 50% of offspring will inherit the abnormal gene copy. Conditions that follow this predictable inheritance pattern are said to follow Mendelian inheritance.
A gene abnormality that occurs as a new event (also known as 'de novo', or a 'sporadic' occurrence) during cell division in an individual after his/her conception. The gene abnormality is therefore not inherited from the individual's parents. The stage of embryogenesis, or later life, when the gene abnormality occurs determines which tissues in the mature individual, and in what percentage of cells in those tissues, the gene abnormality will be found. Mosaicism is the term used when the gene abnormality is only found in a percentage of the individual's cells, and not in all. Whether the individual affected by mosaicism has a health condition or not, depends on which tissues are affected and to what degree (what the percentage of cells is that has the gene abnormality). The abnormality is considered an acquired germline gene abnormality if it is present in the individual's gonadal tissue (egg/sperm) as it may then be transmitted to offspring. If it is present in the individual's tissues (such as brain) but not in gonadal tissue (not in egg/sperm), then it is considered an acquired somatic gene abnormality. In this instance, it cannot be transmitted to the individual's offspring.
Some epilepsies are caused, not by a single gene abnormalities, but by the summed final effect of multiple gene abnormalities/variations ('polygenic'), increasing susceptibility to seizures. Individually, these gene abnormalities/variations are not sufficient to cause a health condition, however their summed effect can increase susceptibility to seizures. Some individuals with polygenic etiologies, will have spontaneous seizures, others have seizures only with additional environmental triggers present, such as increased temperature, viral illness, alcohol ingestion or sleep deprivation. When polygenic and environmental factors are required to result in seizures, this is known as a 'complex' genetic etiology for the epilepsy. Polygenic and complex genetic epilepsies occur at higher frequency in families of affected individuals, but their inheritance pattern is not as easy to predict as for single gene abnormalities. Researching these genetic causes, or testing for them in individual patients, is difficult for the same reason – the epilepsy is due to the combined sum of the effects of many genes and environmental factors.