Epilepsy genes Flashcards
Genes associated with GEFs+ (3)
Important note on these
SCN1A
SCN1B
GABRG2
mutations are seen in only 10-20% of GEFS+ (why genetic testing is not often advised)
Genes associated with Dravet Syndrome
SCN1A (70-80%)
Hyperekplexia
AKA:
Onset (2)
Symptoms (3)
Associated genes (2)
Protein
Treatment of choice
AKA - Stiff baby syndrome
Onset
- usually infancy
- Can be delayed in adolecence / adulthood
Symptoms
- Generalized stiffness
- Nocturnal myoclonus
tonic spasms usually triggered by auditory or generalized stiffness
Associated genes
- GLRA1
- GLRB
Associated protein
- Inhibitory glycine receptor
Treatment of choice: Clonazepam
Epilepsy Genes - Benign Familial neonatal Seizures
- Inheritance
- Identified Genes (2)
- Affected protein
- Outcome
Inheritance: AD
Genes:
- KCNQ2
- KCNQ3
Protein: M-channel subunit of voltage-gated potassium channel
- Benign outcome
Epilepsy Genes: Benign female Neonatal-infantile seizures
- Inheritance
- Identified Gene
- Affected protein
- Outcome/prognosis
Inheritance: Autosomal Dominant
Identified Gene: SCN2A
Protein: sodium channel subunit
Outcome/Prognosis: Benign
- normal development
- Seizures from 2 days to 6 months
- Self-resolve
Epilepsy Genes: Ohtahara Syndrome
- Inheritance:
- Identified Genes (2)
Inheritance: variable
Genes
- STXBP1
- ARX
Epilepsy Genes: Early-onset Spasms
- Inheritance:
- Genes
Inheritance: X-linked (girls only, possibly lethal in males
Gene: CDKL5
Epilepsy Genes: X-linked infantile spasms
- Inheritance
- Gene
- Inheritance: Boys
- Gene: ARX
Epilepsy Genes: Childhood absence epilepsy with Febrile Seizures
- Inheritance
- Gene
- Protein
Inheritance: AD
Gene: GABRG2
Protein: GABAa receptor subunit
Epilepsy Genes: Epilepsy and mental retardation limited to females
Inheritance
Gene
Protein
Inheritance: X-linked (only seen in heterozygous females
Gene: PCDH19
Protein: procadherin
Epilepsy Genes, Early onset Absence Epilepsy
Inheritance
Gene
Protein
Inheritance: Autosomal Dominant
Gene: SLC2A1
Protein: GLUT1 > treat w/ Keto diet
Epilepsy Genes: Juvenile Myoclonic Epilepsy
Inheritance
Gene (2)
Protein (2)
Inheritance: Autosomal Dominant
Genes
- GABRA1 - GABAa receptor
- EFHC1 - EF hand motif protein
Epilepsy Genes: ADNFLE
- Inheritance
- Genes
- affected protein
Inheritance: autosomal Dominant
Genes:
- CHRNA4
- CHRNA1
- CHRNB2
Protein: nicotinic acetylcholine receptor subunits
Epilepsy Genes: Autosomal Dominant partial epilepsy with Auditory features (ADPEAF)
- Inheritance
Gene
Inheritance: Autosomal Dominant
Gene: LGI1
Epilepsy Genes: Myoclonic Epilepsy with Ragged Red Fibers
- Inheritance
- Gene
- Best confirmation test
Inheritance: Mitochondrial
Gene (tRNA)
Diagnosed by muscle biopsy
Epilepsy Genes: Unverricht-Lundborg
- Inheritance
- Gene
- Protein
Inheritance: autosomal recessive
- Gene: EPM1 (CSTB)
- protein: Cystatin B
Epilepsy Genes: Lafora Disease
Inheritance
Gene (2)
Protein (2)
Inheritance: autosomal recessive
Genes
- EPM2A
- NHRC1 (EPM2B)
Proteins
- Laforin
- malin
Epilepsy Genes: Sialidosis
- Inheritance
- Gene
- Affected Protein
- Other test
Inheritance: Autosomal recessive
Gene: NEU
Protein: neuraminidase
Other test: increased urinary oligosaccharides
Epilepsy Genes: Dentatorubral-pallidoluysian atropy (DRPLA)
- Inheritance
- Gene
- Type of disroder
Inheritance: Autosomal dominant
Gene: ATN1
type of disorder: Trinucleotide repeat
Epilepsy Genes: Lissencephaly
Inheritance:
Gene
Specifics about this type of Lissencephaly
Inheritance: autosomal dominant
Gene: LIS1
Specifcs: Posterior predominant
Epilepsy Genes: X-linked lissencephaly / double cortex syndrome / Subcortical band heterotopia
- Inheritance
- Gene
Inheritance: X-linked dominant
Gene: DCX
DCX mutation presentations:
Males
Females
Males
- lissencephaly
- epilepsy
- DMD
Females
- broad heterotopic zone
- Frontally predominant
Epilepsy Genes: Periventricular nodular heterotopia
Inheritance:
Genes (2)
Features specific to second gene mutation
Inheritance:
- X-linked dominant (FLNA)
- Autosomal recessive (ARFGEF2)
- Also with microcephaly
Epilepsy Genes: Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS)
Inheritance: mitochondrial
Gene: tRNA - Leu
Epilepsy Genes: Alpers Syndrome
- Inheritance
- Gene
- Protein
Inheritance: autosomal recessive
Gene: POLG1
Protein: Nuclear gene for DNA polymerase Gamma
Epilepsy Genes: Fragile X
Inheritance
Protein
Type of disorder
Inheritance: autosomal Dominant
Gene: FMR1
Type of disorder: Trinucleotide repeat
Epilepsy Gene: Rett syndrome
- Inheritance
- Gene
Inheritance: x-linked
Gene MECP2
Epilepsy Genes: Angelman syndrome
Genetic test
DNA methylation analysis (UBE3A0
Gene mutations found in Childhood absence epilepsy (2)
GABRG2
GABRA1
Patient with 6 fingers is found to have a hypothalamic hamartoma.
- What condition and gene could be causing this?
- What else should you look for? (4)
Pallister Hall syndrome (LGI-1)
Other features
- Fused fingers
- Bifid epiglottis
- Imperforate anus
- kidney abnormalities
Glut1 disorder
- diagnostic criteria (3)
- Associated mutation
Hypoglycorrhachia with normoglycemia and low-to-normal CSF lactate
- CSF Glucose <60 mg/dL (3.3 mmol/dL) but most cases needs to be <40 mg/dl (2.2 mmol/L)
- CSF: blood glucose ratio <0.4
Associated mutation
- SLC2A1 (90%) - de novo
Patient with intractable absence seizures and mild developmental delays. What should you rule out and how (3)? How common is this?
GLUT1 deficiency syndrome
Tests
- Low lactate
- Glucose <40
- Gene test for SLC2A1
how common
10% of early-onset absence seizure (<4 years)
“buzzword” seizure with ring 20 chromosome syndrome
Nocturnal frontal seizures (confusion / wandering)
Early childhood seizures triggered by fever. Name two genes and ways to differentiate them
A (4)
B(3)
SCN1A
- GEFS+ and Dravet
- typically more with Status epilepticus
- hemiclonic or generalized
- Developmentally initially normal but then plateau/regression
PCD19
- Epilepsy limited to Females with Mental Retardation (EFMR)
- 10+ clusters of brief focl or generalized seizure every few days
- Also Developmentally initially normal but then with plateau/regression
Benign familial Neonatal seizures (BFNS)
- Interitance
- mutations (2) and respective chromosome (2)
- typical seizures (3)
- EEG
