Genetic Epilepsies Flashcards
Autosomal dominant nocturnal frontal lobe epilepsy?
Mutations in the nicotinic acetylcholine receptor
Sodium chloride channel mutations associated epilepsy syndromes
Dravet syndrome, GEFS+
What gene is involved in Familial lateral temporal lobe epilepsy
Leucine-rich glioma inactivated 1 gene, LGI1 gene
GABA receptor associated syndromes?
JME, Absence epilepsy, GEFS+ idiopathic generalize epilepsy, Infantile spasms, Lennox-Gastaut
What are copy number variants?
Variations of DNA sequences at least 1 Kb in length
Can copy number variants be detected by karotyping?
No
What type of epilepsy have copy number variants been associated with?
Generalize epilepsy and intellectual disability
What is the average length of copy number variants?
250 mb
What genes are associated with epilepsy and hemiplegia migraine?
CACNA1A, ATP1A2, and SCN1A
Copy number variants can represent what?
Monogenic disease or act as risk alleles
Copy number variants that cause disease can be found in unaffected family members?
Yes
Can copy number variants be found with karotyping?
No
What subunits of the GABA-A receptor have been associated with epilepsy?
Genes involving the subunits GABR-A1, -B2, -B3, -G2, -D
GABA-A receptor subunit types have been associated with what milder generalized epilepsy syndromes?
JME, Absence, IGE with tonic clinic seizures.
What mildly severe phenotypes have been associated with GABA-A mutations?
MAE, mild epileptic encephalopathy
What severe phenotypes have been associated with GABA-A mutations?
Dravet syndrome, epileptic encephalopthies
What are the predominant EEG findings in patients with GABA-A mutations?
Generalized spike-wave and generalized poly spike-wave, generalized photoparoxysmal response, focal spikes bilaterally frontally and posteriorally
What seizures semiologies are associated with GABA-RA1 mutations?
Tonic clinic and myoclonic are majority but also absence, atonic, tonic, myoclonic-atonic, and status epilepticus
What does the EEG background look like in Angelman syndrome look like?
Resembles hypsarrhythmia but does not show fragmentation during sleep.
What gene mutations would be Associated with brief episodes of thrashing that occur in clusters during sleep?
Genes encoding the nicotinic acetylcholine receptor
What gene is responsible for familial lateral temporal lobe epilepsy with auditory features?
Leucine-rich glioma inactivated 1 (LGI1) gene
Benign familial neonatal epilepsy is associated with mutations in what genes?
KCNQ2 and KCNQ3 potassium channel genes.
What is the testing strategy for possible genetic epilepsies?
Detailed clinical assessment complemented by analysis of the gene single-nucleotide polymorphisms and copy number variants.
In Dravet syndrome what is the pick up of genetic testing?
80% will have a point mutation and 12% will harbor copy number variants (deletions)
What does the term GEFS+ mean?
Genetic epilepsy with febrile seizures plus
In GEFS+ associated genes in family pedigrees?
SCN1A, SCN1B, SCN9A and GABRG2
What is the inheritance pattern in patients with Sturge Weber
Sporadic, random mutation in theGNAQ gene
What is the percentage of Angelman syndrome children have seizures?
70-80%
What is the percentage of children with trisomy 21 have seizures in childhood?
Less than 5%
What is the percentage of children with DiGeorge syndrome have seizures?
21%
What is the percentage of children with fragile X syndrome?
15-20%
What is the only FDA approved indication for VGB in adults?
Refractory focal dyscognitive seizures
What is the reason for altering dosing of LTG when used with VPA?
VPA decreases the clearence of LTG
What is the most common seizure and social outcome for children with Dravet?
Intractable seizures, but with decreased seizures over time, and dependence for some or all activity of daily living
Is benign epilepsy with centrotemporal spikes considered to be a genetic etiology?
Yes
What is the only glucose transporter gene related with epilepsy?
SLC2A1 gene
What other clinical presentations can be seen with SLC2A1 mutations?
Paroxysmal kinesigenic dyskinesia, alternating hemiplegia of childhood.
What other seizure types are associated with mutations in the SLC2A1 gene?
Atypical absence, absence, drops, atonic, and myoclonic
JME is associated with mutations in what gene?
GABA(A)
What is the most common genetic mutation found in migrating partial epilepsy of infancy?
KCNT1
What genes are associated with migrating partial seizures of infancy?
PLCB1, TBC1D24, SCN1A. SCN2A, SLC25A22, and KCNT1
What gene is involved in familial focal epilepsy with variable focu?
DEPDC5
What is a gene involved in inherited focal epilepsies?
DEPDC5
What gene is involved with developmental delay, epilepsy, and neonatal diabetes?
KCNJ11
What are the range of epilepsy syndromes associated with DEPDC5?
Focal epilepsy with variable focus, autosomal dominant nocturnal frontal lobe epilepsy, facial temporal lobe epilepsy and focal cortical dysphasia
