Epilepsy genes Flashcards by Susan Fong

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)

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Genes associated with Dravet Syndrome

SCN1A (70-80%)

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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

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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

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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

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Epilepsy Genes: Ohtahara Syndrome
- Inheritance:
- Identified Genes (2)

Inheritance: variable
Genes
- STXBP1
- ARX

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Epilepsy Genes: Early-onset Spasms
- Inheritance:
- Genes

Inheritance: X-linked (girls only, possibly lethal in males
Gene: CDKL5

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Epilepsy Genes: X-linked infantile spasms
- Inheritance
- Gene

Inheritance: Boys
Gene: ARX

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Epilepsy Genes: Childhood absence epilepsy with Febrile Seizures
- Inheritance
- Gene
- Protein

Inheritance: AD
Gene: GABRG2
Protein: GABAa receptor subunit

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Epilepsy Genes: Epilepsy and mental retardation limited to females
Inheritance
Gene
Protein

Inheritance: X-linked (only seen in heterozygous females
Gene: PCDH19
Protein: procadherin

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Epilepsy Genes, Early onset Absence Epilepsy
Inheritance
Gene
Protein

Inheritance: Autosomal Dominant
Gene: SLC2A1
Protein: GLUT1 > treat w/ Keto diet

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Epilepsy Genes: Juvenile Myoclonic Epilepsy
Inheritance
Gene (2)
Protein (2)

Inheritance: Autosomal Dominant
Genes
- GABRA1 - GABAa receptor
- EFHC1 - EF hand motif protein

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Epilepsy Genes: ADNFLE
- Inheritance
- Genes
- affected protein

Inheritance: autosomal Dominant
Genes:
- CHRNA4
- CHRNA1
- CHRNB2
Protein: nicotinic acetylcholine receptor subunits

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Epilepsy Genes: Autosomal Dominant partial epilepsy with Auditory features (ADPEAF)
- Inheritance
Gene

Inheritance: Autosomal Dominant
Gene: LGI1

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Epilepsy Genes: Myoclonic Epilepsy with Ragged Red Fibers
- Inheritance
- Gene
- Best confirmation test

Inheritance: Mitochondrial
Gene (tRNA)
Diagnosed by muscle biopsy

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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