Genetic Epilepsies

Genetic Epilepsy

Understanding genetics can be complicated. There are hyperlinks throughout this resource to try and help explain genetic words (click on a word highlighted in colour and this will link to a website explaining that word). You can also visit the links / resources tab for more resources to help explain genetics.

A “genetic” epilepsy is caused directly by a change in the sequence (spelling) of a gene associated with epilepsy and is relatively rare. A genetic cause means that there is a change in the instructions (or genes) that make us who we are. There are other causes of epilepsy, including head trauma and brain infections.

Genetic testing is useful in some types of epilepsy, such as the more severe genetic epilepsies that involve other symptoms (for example, developmental delay, intellectual disability, autism, behavioural issues, sleep disturbance, poor head growth (microcephaly) and/or visual problems) and that require multiple medications. These more severe epilepsies are often caused by a change in a single gene that is important in brain functioning. Your GP or specialist will decide if genetic testing might be worth considering for your child.

Occasionally where there is a clear family history of epilepsy, genetic testing may also be helpful where an inherited form of epilepsy is suspected.

For other types of epilepsy (e.g. childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy), there are likely a number of genetic changes that combine to increase the person’s chance/risk of having epilepsy. This is called polygenic (the combination of multiple genes) or multifactorial (the combination of multiple genes and the environment) inheritance. In addition, these epilepsies are often well controlled with medications. The chance of finding one single meaningful change in one gene in these forms of epilepsy is low, and therefore genetic testing is often not offered to these individuals or families with these types of epilepsy at this current time.

Having a “genetic” epilepsy does not always mean it is “inherited”. Sometimes, the genetic changes are new events that have not been inherited. Further information on genetic inheritance can be found in the “Genetic Inheritance” tab above.

 

Genetic Inheritance

The instructions that make us who we are (called genes) are carried in pairs. Genes are made up of thousands of molecules of DNA. DNA is made up of four proteins that are in a specific sequence within each gene. These genes are bunched together onto structures called chromosomes. We inherit one copy of each gene (and therefore each chromosome) from each of our parents. Additional information on DNA, chromosomes and genes can be found here.

A genetic epilepsy can occur in multiple generations in a family or be unique to one person, and may cause different symptoms in different members of the same family. There are five main ways genetic epilepsies can occur in families (there are other rare exceptions which will not be explored here but can be explained by your genetics team):

1.       A new genetic change in the affected person

  • Inheritance: This type of change is genetic, but it is not inherited from the parents, who do not have epilepsy.
  • This is called a ‘de novo’ (or new) event, resulting from a change in only one of the copies of our genes. The other copy is still working, but some particular genes require two working copies in order to provide instructions for general good health. This pattern of inheritance is called Autosomal Dominant inheritance. More details about this form of inheritance can be found here.
  • Implications for family planning:
    • Parents of a child with a de novo change have a low, but not zero, chance of having another affected child. This is because the genetic change may be present in a pocket of eggs or sperm (‘gonadal mosaicism’). This possibility can be discussed in more detail with your genetics specialist.
    • There is a 1 in 2 (50%) chance that an affected person will pass the condition on to their future children.

 

2.       An inherited genetic change from an affected parent

  • Inheritance: This change has been inherited from a parent who also has the same condition.
  • This is called ‘Autosomal Dominant inheritance’, resulting from a change in only one of the copies of our genes. The other copy is still working, but this particular gene requires two working copies in order to provide instructions for general good health. More details about this form of inheritance can be found here.
  • Implications for family planning: There is a 50% chance that an affected individual will pass the condition on to their future children.

 

3.       A combination of genetic changes from each parent

  • Inheritance: These changes are inherited from the affected individuals’ parents, although the parents themselves will be unaffected.
  • This is called Autosomal Recessive inheritance. As each parent has two copies of every gene, in their eggs or sperm, they only pass on one copy. One copy from each parent combines to create their child. Should the parents both carry a change in the same gene, the child is at risk of inheriting both changed copies and having the genetic condition. There is often no family history of the condition. More details about this form of inheritance can be found here.
  • Implications for family planning: Parents of children with recessive conditions will have a 1 in 4 (25%) chance of having another baby with the same condition. Affected individuals will be unlikely to pass the condition on to their own children, but should have their partner screened prior to family planning (to avoid the low risk of a partner being a carrier).

 

4.       A genetic condition which only affects boys

  • Inheritance: The condition may occur for the first time in an affected boy, or may be inherited from a carrier girl. There may be a family history of affected boys or no family history at all.
  • This is called X-linked recessive inheritance. The genes, which provide instructions to make a boy or a girl, are located on the X and Y chromosomes. Girls have two X chromosomes and boys have an X and Y. If there is a change in a gene located on the X chromosome, girls can carry one change and one working copy and be well and healthy (called a ‘carrier’). Boys have only one X chromosome and therefore if they have a change in their X chromosome they will have the genetic condition. More details about this form of inheritance can be found here.
  • Implications for family planning: Girls who are carriers have a 1 in 4 (25%) chance of having an affected boy. Boys who have the condition cannot have an affected son (as they will pass their Y chromosome to their sons). Boys who have the condition will pass their changed X chromosome to their daughters, making all their daughters carriers.

 

5.      A genetic condition which only affects girls

  • Inheritance: The condition may occur for the first time in an affected girl (the most common), or may be inherited from a mildly affected mother or an unaffected father (rare). There may be a family history of affected girls or no family history at all.
  • This is called X-linked dominant inheritance. The genes which provide instructions to make a boy or a girl are located on the X and Y chromosomes. Girls have two X chromosomes and boys have an X and Y. If there is a change in a gene located on the X chromosome, some genes on the X chromosome are important in females and require two functioning copies in order to be well and healthy. If an affected girl has a change in one X chromosome, this causes the condition to occur.
  • These conditions can have a wide range of variability, meaning that some girls can carry the change and be unaffected, through to a girl who is severely affected.
  • Boys who carry the variant are usually unaffected or more mildly affected.
  • Implications for family planning:
    • Parents of a child with a de novo change (in this case on the X chromosome) have a low, but not zero, chance of having another affected child. This will be the majority of patients with X-linked dominant changes. This is because the genetic change may be present in a pocket of eggs or sperm (‘gonadal mosaicism’). This possibility can be discussed in more detail with your genetics specialist.
    • A father who carries a variant on the X chromosome (but is asymptomatic) will have a 50% chance of having an affected daughter, and a 50% chance of having an unaffected son.
    • A mother who carries a change in an X-linked dominant gene has a 25% chance of an affected daughter, a 25% chance of an unaffected daughter, a 25% chance of an unaffected (non-carrier) son, and a 25% chance of having a boy who is unaffected but has the change (this would have implications for the boys children).

 

Genetic Testing

A “genetic” epilepsy is caused directly by a change in the sequence (spelling) of a gene associated with epilepsy and is relatively rare. A genetic cause means that there is a change in the instructions (or genes) that make us who we are. There are other causes of epilepsy, including head trauma and brain infections.

Genetic testing is useful in some types of epilepsy, such as the more severe genetic epilepsies that involve other symptoms (for example, developmental delay, intellectual disability, autism, behavioural issues, sleep disturbance, poor head growth (microcephaly) and/or visual problems) and that require multiple medications. These more severe epilepsies are often caused by a chang