Did You Know: Epilepsy (Seizure Disorder)

Epilepsy is a group of brain disorders in which brain activity is abnormal and leads to seizures. The term epilepsy describes a range of conditions. These conditions vary based on clinical factors, such as seizure types, ages of onset, and more, but epilepsies are one of the most common types of neurological disorders, affecting 1 in 100 Canadians.¹ Approximately 20–30% of epilepsy cases are caused by acquired conditions, such as stroke, tumor, or head injury, while the remaining 70–80% of cases are believed to be caused by a combination of genetic and environmental factors.²

 Genetics and Epilepsy

Subtypes of epilepsies can be categorized into three major classes:²

• Generalized epilepsies
• Focal epilepsies
• Encephalopathic epilepsies

Genetic forms of epilepsy can be isolated or syndromic:³

• Isolated: The genetic change leads to a form of epilepsy (e.g.,: an ion-channel mutation)
• Syndromic: Epilepsy is one feature that, along with other clinical findings, leads to a recognizable condition referred to as a syndrome (e.g.,: Rett syndrome)  

Reasons for Genetic Testing

Confirmation of a clinical diagnosis through genetic testing can direct medical management, help predict progression of the disease, and provide essential information related to risk for relatives. In particular, testing is recommended for:

• Individuals with a family history of epilepsy and presentation of the most common symptoms
• Individuals without a positive family history, but who have experienced unprovoked seizures
• Individuals with a negative but suspected family history, in order to perform proper genetic counselling (prenatal testing is possible in families with affected individuals where the genetic cause is identified)

 LifeLabs Genetics offers the following Next-Generation Sequencing panels (Sequencing and Copy Number Variant analyses)

• Comprehensive Epilepsy Panel: ACY1, ADSL, ALDH7A1, AMT, ARHGEF15, ARHGEF9, ARX, ASAH1, CACNA1H, CACNB4, CDKL5, CERS1, CHRNA2, CHRNA4, CHRNB2, CLCN2, CLN3, CLN5, CLN6, CLN8, CNTNAP2, CPA6, CPT2, CSTB, CTSD, CTSF, DEPDC5, DNAJC5, EFHC1, EPM2A, FOLR1, FOXG1, GABRA1, GABRB3, GABRD, GABRG2, GAMT, GCSH, GLDC, GOSR2, GRIN2A, GRIN2B, GRN, JRK, KCNA2, KCNJ10, KCNMA1, KCNQ2, KCNQ3, KCNT1, KCTD7, LGI1, MAPK10, MBD5, MECP2, MEF2C, MFSD8, MTHFR, MTOR, NEDD4L, NEU1, NHLRC1, NOL3, NRXN1, PCDH19, PIGA, PIGO, PIGV, PLCB1, PNKP, PNPO, POLG, PPT1, PRICKLE1, PRICKLE2, PRRT2, QARS, RBFOX1, RBFOX3, RNASEH2A, RNASEH2B, RNASEH2C, ROGDI, SAMHD1, SCARB2, SCN1A, SCN1B, SCN2A, SCN3A, SCN8A, SCN9A, SGCE, SLC13A5, SLC19A3, SLC25A12, SLC25A22, SLC2A1, SLC35A2, SLC6A8, \SLC9A6, SPTAN1, SRPX2, ST3GAL3, ST3GAL5, STXBP1, SYN1, SYNGAP1, SZT2, TBC1D24, TBCE, TCF4, TPP1, TREX1, TSC1, TSC2, UBE3A, WWOX, ZEB2
• Epileptic Encephalopathy Panel: ACY1, ADSL, ALDH7A1, AMT, ARHGEF9, ARX, CDKL5, CNTNAP2, CPT2, FOLR1, FOXG1, GABRG2, GAMT, GCSH, GLDC, GRIN2A, GRIN2B, KCNA2, KCNJ10, KCNQ2, MAPK10, MECP2, MTHFR, NRXN1, PCDH19, PLCB1, PNKP, PNPO, PRRT2, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, SCN1A, SCN1B, SCN2A, SCN8A, SCN9A, SLC19A3, SLC25A22, SLC2A1, SLC9A6, SPTAN1, STXBP1, TBCE, TCF4, TREX1, UBE3A, ZEB2
• Early Infantile Epileptic Encephalopathy (EIEE) Panel: AARS, ALG13, ARHGEF9, ARV1, ARX, CACNA1A, CDKL5, DNM1, DOCK7, EEF1A2, FRRS1L, GABRA1, GABRB3, GNAO1, GRIN2B, GUF1, HCN1, ITPA, KCNA2, KCNB1, KCNQ2, KCNT1, NECAP1, PCDH19, PIGA, PLCB1, PNKP, SCN1A, SCN2A, SCN8A, SCN9A, SLC12A5, SLC13A5, SLC1A2, SLC25A12, SLC25A22, SLC35A2, SPTAN1, ST3GAL3, STXBP1, SZT2, TBC1D24, WWOX
• Hereditary Epilepsy (partial/focal) Panel: CACNA1H, CACNB4, CHRNA2, CHRNA4, CHRNB2, CLCN2, CPA6, DEPDC5, EFHC1, GABRA1, GABRB3, GABRD, GABRG2, JRK, KCNMA1, KCNQ2, KCNQ3, KCNT1, LGI1, SCN1A, SCN1B, SCN2A, SCN8A, SCN9A, SLC2A1, SRPX2
• Childhood Epilepsy (absence) Panel: CACNA1H, GABRA1, GABRB3, GABRG2, JRK, SLC2A1
• Dravet Syndrome Panel: SCN1A, GABRG2, SCN2A, SCN9A
• Epilepsy (generalized) with Febrile Seizures Panel: GABRD, GABRG2, SCN1A, SCN1B, SCN2A, SCN9A
• Myoclonic Epilepsy Panel: ASAH1, CACNB4, CERS1, CSTB, EFHC1, EPM2A, GABRA1, GABRD, GLDC, GOSR2, NEU1, NHLRC1, NOL3, POLG, PRICKLE1, PRICKLE2, SCARB2, SGCE

 References

1. Epilepsy Ontario. What is Epilepsy? http://epilepsyontario.org/about-epilepsy/what-is-epilepsy/
2. Myers and Mefford (2015) Advancing epilepsy genetics in the genomic era. Genome Med. 7:91.
3. Steinlein (2008) Genetics and epilepsy. Dialogues Clin Neurosci. 10(1):29-38.