Genetics of Epilepsy

Question 1

Epilepsy prevalence

Answer 1

Second most common neurological disorder affecting 65 million persons worldwide

Question 2

Etiological division of epilepsies:

Answer 2

• Genetic: the epilepsy is the direct result of a known or inferred genetic defect(s). Seizures are the core symptom of the disorder. Genetic does not exclude the possibility of environmental factors contributing.
• Structural-Metabolic: there is a distinct structural or metabolic condition or disease present that has been demonstrated to be associated to the development of epilepsy. Structural lesions of course include acquired disorders such as stroke, trauma, tumor or infection…
• Unknown: the nature of the underlying cause is as yet unknown.

Question 3

Epilepsy types pie chart:

Answer 3

• 50% genetic
• 35% - structural metabolic
  
  • 10% stroke
  • 8% congenital malformations
  • 5.5% head injury
  • 4.1% cancer
  • 3.5% degenerative
  • 2.5% infection
• 15% unknown

Question 4

Types of genetic epilepsy syndromes:

Answer 4

• Genetic Generalized Epilepsies (GGE)
• Genetic Focal Epilepsies (GFE)
• Epileptic Encephalopathies (EE)

Question 5

Forms of genetic variations at chromosome level:

Answer 5

• inversion
• translocation
• duplication
• ring chromosome
• deletion

Question 6

Differences between mutations & polymorphisms

Answer 6

Mutations:

• 1% frequency in general population
• common (3mil SNPs in the genome)
• ancient
• many have no effects, some may predispose people to disease or influence their response to drugs

Question 7

Genetic epilepsy - types of inheritance:

Answer 7

• 5% Mendelian
• 95% complex
  SNPs in several or multiple susceptibility genes with small additive effects (polygenic) + environment are responsible for the epilepsy

Question 8

Majority of epilepsy-related genes tend to encode:

Answer 8

• ion channels (great majority)
• proteins involved in brain formation
• proteins involved in brain metabolism

Question 9

Describe juvenile myoclonic epilepsy:

Answer 9

• 12-30% of all epilepsies
• most common form of Genetic Generalized epilepsy
• 60% concordance in MZT
• 50% of familial history
  • Onset in adolescence (12-18 years)
  • Typical clinical symptoms:
  – myoclonic seizure (brief, shock-like jerks of a muscle or a group of muscles, generally on arms)
  – generalized tonico-clonic seizures (convulsion)
  – sometimes absence seizures (loss of conscience)

Question 10

Structural abnormalities associated with juv myoclonic epilepsy:

Answer 10

Atrophy in:
- corpus callosum
- hippocampus
- thalamus
Increased grey matter (microdysgenesis)
- frontal lobe