Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing.

What is genetics?

Genetics is the study of heredity or how different characteristics (traits) are passed from a parent to a child. A person inherits these traits from their parents. Each person has several thousand genes that are made up of DNA. Genes are packaged into larger structures called chromosomes. Chromosomes are present in almost every human body cell. Genetics play a part in many types of epilepsy. 

The Role of Genetics in Epilepsy

Advances in science and technology can help identify molecular defects (for example, deletions or mutations) that contribute to the genetics of some types of epilepsy. Genetic testing helps scientists and physicians better understand how various genes may interact to produce a specific epilepsy syndrome. This genetic information may give people with epilepsy and their families more detail about their specific epilepsy syndrome. Several epilepsies have a genetic component and we know that epilepsy can run in families.

How is genetic testing done in people with epilepsy?

Usually, genetic testing requires a blood or saliva sample to be taken from the person with epilepsy. The sample is then sent to a laboratory for genetic testing. The test looks at the DNA in the person’s blood or saliva. The sample is analyzed for mutations or changes in a subset of genes that have a known association with different types of epilepsy. 

What types of genetic disorders are there?

There are five types of genetic disorders:

  • single gene disorders that result when a mutation causes a single gene to be altered or missing
  • multifactorial/complex disorders that are related to mutations in a number of genes and are often also associated with an environmental influence
  • mitochondrial disorders that result from mutations in DNA found in mitochondria; mitochondrial gene mutations cause a problem with how energy is produced in cells.
  • chromosomal disorders that occur when entire chromosomes are missing or changed
  • epigenetic disorders that are related to changes in the activity of genes, rather than a mutation in the structure of DNA

What are some examples of epilepsy syndromes where genetic testing may be helpful?

The inheritance of epilepsy is frequently complex. Genetic disorders can cause epilepsy alone or may cause a syndrome that affects various parts of the body as well as epilepsy. Some epilepsy syndromes are known to have a genetic basis, but the gene or genes that cause the syndrome have not yet been identified. Finally, some genetic disorders arise spontaneously through new gene mutations. 

More than 20 different syndromes with epilepsy as a main feature have been mapped to specific genes. Many more single gene disorders that cause brain abnormalities or metabolic disorders have epilepsy as a primary symptom. Also, scientists have identified mutations in genes that control sodium, potassium, and calcium channels that can also cause epilepsy. 

It’s important to note that genetic testing in some epilepsy syndromes has already played a significant role in clinical practice. This has been particularly true for people with epileptic encephalopathies that begin in infancy and early childhood. For example, this may include:

  • Dravet syndrome - more than 70% of people have mutations of SCN1A.
  • Epilepsy limited to females with mental retardation – involves the PCDH19 gene.

More challenging at this time are the subgroup of genetic generalized epilepsies (GGE) that include childhood absence epilepsy, juvenile absence epilepsy, juvenile myoclonic epilepsy, photosensitive epilepsy, and generalized tonic-clonic seizures. GGE has a complex genetic inheritance pattern. This subset of epilepsies present a challenge, and currently we have little information about the genes that are implicated in GGE. 

However, genetic testing still may have a key role to play. Over time, as more information is collected, the cause of these epilepsies will be better understood. Knowing the cause may improve testing, diagnosis, clinical treatment, and family counseling. 

Some Epilepsy Syndromes Seen with Genetic Disorders

Below are listed some of the epilepsy syndromes that may result from genetic disorders. New genes involved in epilepsy are being identified regularly, and the genetics of epilepsy spectrum continues in a period of rapid growth. 

Single Gene Epilepsy Syndromes

  • Autosomal dominant partial epilepsy with variable foci
  • Autosomal dominant nocturnal frontal lobe epilepsy
  • Benign familial neonatal convulsions
  • Benign infantile familial convulsions
  • Familial temporal lobe epilepsy
  • Generalized epilepsy with febrile seizures plus
  • Progressive myoclonus epilepsies
  • Epileptic encephalopathies (Dravet, PCDH19)

Other Single Gene Disorders that Can Manifest as Epilepsy

  • Neurofibromatosis 1
  • Tuberous sclerosis
  • Fragile X  syndrome
  • Rett syndrome
  • Acute intermittent porphyria
  • Leukodystrophies
  • Mucopolysaccharidoses (Sanfilippo syndrome)

Other Inherited Metabolic Conditions that May Cause Seizures

  • Phenylketonuria (PKU)
  • Galactosemia
  • Tay-Sachs disease
  • Pseudohypoparathyroidism
  • Pyridoxine dependency
  • Peroxisomal disorders

Multifactorial Disorders

  • Myoclonic-astatic epilepsy
  • Benign epilepsy of childhood with centrotemporal spikes 
  • Benign myoclonic epilepsy of infancy
  • Juvenile myoclonic epilepsy
  • Childhood absence epilepsy
  • Juvenile absence epilepsy
  • Photosensitive epilepsy

Mitochondrial Disorders

  • Myoclonus epilepsy and ragged red fibers (MERRF)

Chromosomal Disorders

  • Down syndrome 
  • Edwards syndrome
  • Patau syndrome
  • Wolf-Hirschhorn syndrome
  • Angelman syndrome
  • Ring chromosome abnormalities

How can genetic testing help people with epilepsy, their families, and their health care team? 

  • Genetic testing in a person with epilepsy can help confirm a specific diagnosis. It may also give information about other associated neurologic or medical conditions that may arise over time. 
  • It may assist your neurologist with selecting an appropriate seizure medication and also with expectations regarding appropriate seizure control. Genetic information may also influence whether or not a specialized diet, such as the ketogenic diet, is recommended. 
  • Genetic information may help to limit unnecessary or invasive testing. 
  • Genetic testing may assist with understanding the prognosis or outlook of a person’s epilepsy and provides a basis for further genetic counseling for families. 
Authored by: Elaine Kiriakopoulos MD | Drug Resistant and Rare Epilepsies Editor on 9/2015

"Over the past decade, the scientific and medical community has made significant advances in the field of DNA sequencing. These advancements have accelerated the pace at which clinicians are able to understand, diagnose, and, at times, direct treatment for various diseases, including neurological diseases. As more individuals are sequenced, we learn more about the linkages between our unique DNA makeup and how to manage certain diseases, including epilepsy. We owe it to the children we serve to collaborate together and put our best foot forward in advancing these efforts."

Brian McKernan
Chief Executive Officer
Courtagen Life Sciences