Epilepsy

Question 1

(Focal or Generalized) epilepsies are most likely to be genetic in etiology.

Answer 1

Generalized

Question 2

Which patients are best served by genetic testing for epilepsy?

Answer 2

treatment resistant epilepsy of unknown etiology

Question 3

outpatient pediatric patient with epilepsy, what is order of genetic tests?

Answer 3

1. panel
2. WES (not 1st b/c can miss small sequencing changes)
3. CMA (del/dup do not commonly cause seizures)

Question 4

Most important epilepsy gene

Answer 4

SCN1A
Dravet syndrome

many epilepsy genes have CN in name for channel, S = sodium, K = potassium

Question 5

Reasons for genetic testing in epilepsy

Answer 5

1. targeted therapies (& therapies not to use)
2. prognosis info
3. recurrence risk (most are AD/de novo, but some are inherited)

Question 6

Why is detection of SCN1A important in epilepsy patients?

Answer 6

• decreased function of sodium channels (LOS variant)
• sodium channel blockers are often used in epilepsy, but these patient should NOT have that type of drug
• other end: SCN2A = GOF variant, overactive sodium channel, so this same drug would be great for them

Question 7

KCNT1-related epilepsy

Answer 7

50% mortality by 10yo
encephalopathy
gain of function

Question 8

Antisense oligonucleotides

Answer 8

• in development for epilepsy
• degrade RNA or mdmify gene splicing

common drug in neuro space