Genetic Epilepsies

Question 1

Autosomal dominant nocturnal frontal lobe epilepsy?

Answer 1

Mutations in the nicotinic acetylcholine receptor

Question 2

Sodium chloride channel mutations associated epilepsy syndromes

Answer 2

Dravet syndrome, GEFS+

Question 3

What gene is involved in Familial lateral temporal lobe epilepsy

Answer 3

Leucine-rich glioma inactivated 1 gene, LGI1 gene

Question 4

GABA receptor associated syndromes?

Answer 4

JME, Absence epilepsy, GEFS+ idiopathic generalize epilepsy, Infantile spasms, Lennox-Gastaut

Question 5

What are copy number variants?

Answer 5

Variations of DNA sequences at least 1 Kb in length

Question 6

Can copy number variants be detected by karotyping?

Answer 6

No

Question 7

What type of epilepsy have copy number variants been associated with?

Answer 7

Generalize epilepsy and intellectual disability

Question 8

What is the average length of copy number variants?

Answer 8

250 mb

Question 9

What genes are associated with epilepsy and hemiplegia migraine?

Answer 9

CACNA1A, ATP1A2, and SCN1A

Question 10

Copy number variants can represent what?

Answer 10

Monogenic disease or act as risk alleles

Question 11

Copy number variants that cause disease can be found in unaffected family members?

Answer 11

Yes

Question 12

Can copy number variants be found with karotyping?

Answer 12

No

Question 13

What subunits of the GABA-A receptor have been associated with epilepsy?

Answer 13

Genes involving the subunits GABR-A1, -B2, -B3, -G2, -D

Question 14

GABA-A receptor subunit types have been associated with what milder generalized epilepsy syndromes?

Answer 14

JME, Absence, IGE with tonic clinic seizures.

Question 15

What mildly severe phenotypes have been associated with GABA-A mutations?

Answer 15

MAE, mild epileptic encephalopathy

Question 16

What severe phenotypes have been associated with GABA-A mutations?

Answer 16

Dravet syndrome, epileptic encephalopthies

Question 17

What are the predominant EEG findings in patients with GABA-A mutations?

Answer 17

Generalized spike-wave and generalized poly spike-wave, generalized photoparoxysmal response, focal spikes bilaterally frontally and posteriorally

Question 18

What seizures semiologies are associated with GABA-RA1 mutations?

Answer 18

Tonic clinic and myoclonic are majority but also absence, atonic, tonic, myoclonic-atonic, and status epilepticus

Question 19

What does the EEG background look like in Angelman syndrome look like?

Answer 19

Resembles hypsarrhythmia but does not show fragmentation during sleep.

Question 20

What gene mutations would be Associated with brief episodes of thrashing that occur in clusters during sleep?

Answer 20

Genes encoding the nicotinic acetylcholine receptor

Question 21

What gene is responsible for familial lateral temporal lobe epilepsy with auditory features?

Answer 21

Leucine-rich glioma inactivated 1 (LGI1) gene

Question 22

Benign familial neonatal epilepsy is associated with mutations in what genes?

Answer 22

KCNQ2 and KCNQ3 potassium channel genes.

Question 23

What is the testing strategy for possible genetic epilepsies?

Answer 23

Detailed clinical assessment complemented by analysis of the gene single-nucleotide polymorphisms and copy number variants.

Question 24

In Dravet syndrome what is the pick up of genetic testing?

Answer 24

80% will have a point mutation and 12% will harbor copy number variants (deletions)

Question 25

What does the term GEFS+ mean?

Answer 25

Genetic epilepsy with febrile seizures plus

Question 26

In GEFS+ associated genes in family pedigrees?

Answer 26

SCN1A, SCN1B, SCN9A and GABRG2

Question 27

What is the inheritance pattern in patients with Sturge Weber

Answer 27

Sporadic, random mutation in theGNAQ gene

Question 28

What is the percentage of Angelman syndrome children have seizures?

Answer 28

70-80%

Question 29

What is the percentage of children with trisomy 21 have seizures in childhood?

Answer 29

Less than 5%

Question 30

What is the percentage of children with DiGeorge syndrome have seizures?

Answer 30

21%

Question 31

What is the percentage of children with fragile X syndrome?

Answer 31

15-20%

Question 32

What is the only FDA approved indication for VGB in adults?

Answer 32

Refractory focal dyscognitive seizures

Question 33

What is the reason for altering dosing of LTG when used with VPA?

Answer 33

VPA decreases the clearence of LTG

Question 34

What is the most common seizure and social outcome for children with Dravet?

Answer 34

Intractable seizures, but with decreased seizures over time, and dependence for some or all activity of daily living

Question 35

Is benign epilepsy with centrotemporal spikes considered to be a genetic etiology?

Answer 35

Yes

Question 36

What is the only glucose transporter gene related with epilepsy?

Answer 36

SLC2A1 gene

Question 37

What other clinical presentations can be seen with SLC2A1 mutations?

Answer 37

Paroxysmal kinesigenic dyskinesia, alternating hemiplegia of childhood.

Question 38

What other seizure types are associated with mutations in the SLC2A1 gene?

Answer 38

Atypical absence, absence, drops, atonic, and myoclonic

Question 39

JME is associated with mutations in what gene?

Answer 39

GABA(A)

Question 40

What is the most common genetic mutation found in migrating partial epilepsy of infancy?

Answer 40

KCNT1

Question 41

What genes are associated with migrating partial seizures of infancy?

Answer 41

PLCB1, TBC1D24, SCN1A. SCN2A, SLC25A22, and KCNT1

Question 42

What gene is involved in familial focal epilepsy with variable focu?

Answer 42

DEPDC5

Question 43

What is a gene involved in inherited focal epilepsies?

Answer 43

DEPDC5

Question 44

What gene is involved with developmental delay, epilepsy, and neonatal diabetes?

Answer 44

KCNJ11

Question 45

What are the range of epilepsy syndromes associated with DEPDC5?

Answer 45

Focal epilepsy with variable focus, autosomal dominant nocturnal frontal lobe epilepsy, facial temporal lobe epilepsy and focal cortical dysphasia