Epilepsy Panel

Epilepsy is a complex disorder that can be caused by various genetic factors. At IntroLab in Belgrade, a specialized genetic testing panel for epilepsy is available, allowing for the identification of relevant genetic mutations. The epilepsy panel aids in establishing an accurate diagnosis and customizing treatment, offering patients and their families essential information for better epilepsy management.

What is epilepsy?

Epilepsy is a neurological disorder characterized by recurrent, unprovoked seizures caused by abnormal and synchronized activity of neurons in the brain. It is one of the most common neurological conditions. Approximately 20-30% of epilepsy cases are caused by acquired conditions such as head injuries or stroke, while the remaining 70-80% are believed to be the result of one or more genetic factors.

Types of epilepsy

The main types of epilepsy are generally classified based on the type of seizures, underlying causes, and the parts of the brain affected. Here are some of the primary types of epilepsy:

Generalized epilepsy

Generalized epilepsy involves seizures that begin simultaneously in both hemispheres of the brain. These seizures can cause loss of consciousness and uncontrolled body movements. Some of the main subtypes of generalized epilepsy include:

• Generalized tonic-clonic seizures (grand mal): Also known as grand mal seizures, these are characterized by a sudden loss of consciousness, body stiffness (tonic phase), followed by rhythmic muscle jerking (clonic phase).
• Absence seizures (petit mal): During these seizures, a person may briefly “zone out,” staring blankly and becoming unresponsive. These seizures usually last a few seconds and are often seen in children.
• Myoclonic seizures: These seizures cause quick, brief muscle jerks, typically in the arms and legs. The person usually remains conscious during the seizure.
• Atonic seizures (drop seizures): These are characterized by a sudden loss of muscle tone, which can lead to falls or injuries as the person loses control of their muscles.

Focal (partial) epilepsy

Focal epilepsy involves seizures that originate in a specific area of the brain. Symptoms depend on the brain region affected. Focal seizures are further classified into:

• Simple focal seizures: These seizures do not cause a loss of consciousness. A person may experience unusual sensations, such as smells, tastes, or tingling sensations. Motor symptoms, such as twitching in a part of the body, may also occur.
• Complex focal seizures: These seizures alter consciousness or cause a loss of awareness. A person may appear confused, stare blankly, or engage in repetitive movements (automatisms), such as chewing or hand rubbing.
• Secondary generalized seizures: These seizures begin as focal but then spread to both hemispheres of the brain, leading to a generalized tonic-clonic seizure.

Idiopathic epilepsy

Idiopathic epilepsy occurs without a clearly defined cause and is often genetically influenced. These seizures can be either generalized or focal. Idiopathic epilepsies typically have a better prognosis and are often successfully managed with medication.

Symptomatic epilepsy

Symptomatic epilepsy results from an identifiable cause, such as head injuries, stroke, brain infections, tumors, or genetic disorders. Diagnosing this type of epilepsy often involves identifying the underlying cause through additional medical tests.

Cryptogenic epilepsy

Cryptogenic epilepsy is diagnosed when an underlying cause for the seizures is suspected, but it cannot be identified even after thorough medical examinations. These cases are often referred to as cryptogenic, meaning the cause remains hidden or unknown.

Status epilepticus

Although not a type of epilepsy, status epilepticus is a medical emergency characterized by a seizure lasting longer than five minutes or a series of seizures without a return to consciousness in between. This condition requires immediate medical intervention to prevent permanent brain damage.

What are the symptoms of epilepsy?

Epilepsy symptoms can vary depending on the type of seizure and the area of the brain affected. Common symptoms include:

• Convulsions: Uncontrolled body movements and muscle spasms.
• Loss of consciousness: A person may lose consciousness and collapse.
• Behavioral changes: Seizures can lead to changes in mood, feelings, or behavior.
• Sensory experiences: Some individuals may experience tingling, dizziness, or unusual sensations before a seizure.
• Loss of consciousness with a blank stare: Some seizures involve a brief loss of consciousness where the person appears to be staring blankly.

Why is genetic testing for epilepsy important?

Genetic testing can offer insights into the causes of epilepsy. Identifying specific genetic mutations can assist doctors in understanding the underlying cause of seizures and in developing personalized treatments. This is particularly crucial for individuals who do not respond to standard treatments or for children who develop epilepsy at an early age.

Types of genetic testing

Several types of genetic testing can be used to diagnose epilepsy:

• Epilepsy panel: Specialized panels analyze specific genes associated with epilepsy. At IntroLab Laboratory in Belgrade, this panel includes the analysis of various genes, including SCN1A, PCDH19, KCNQ2, and others.
• Exome sequencing: This method sequences all the coding genes in the human genome, which can help identify rare mutations.
• Targeted gene sequencing: Focuses on specific genes that are suspected to be involved in epilepsy.
• Microdeletion and microduplication tests: These tests look for small losses or gains of genetic material that may contribute to epilepsy.

What are the most common genetic tests for epilepsy?

The most commonly used test is the epilepsy panel. Utilizing the latest genome analysis technology—Next Generation Sequencing (NGS)—this panel analyzes the following genes:

AARS, ABAT, ABCA2, ABCD1, ACTL6B, ACY1, ADAM22, ADAR, ADNP, ADPRHL2, ADSL, AFG3L2, AGA, AIFM1, AIMP1, ALDH3A2, ALDH5A1, ALDH7A1, ALG13, ALG6, ALKBH8, AMACR, AMT, ANKRD11, AP2M1, AP3B2, AP4B1, AP4E1, AP4M1, AP4S1, APOPT1, ARG1, ARHGEF9, ARID1B, ARSA, ARV1, ARX, ASAH1, ASNS, ASPA, ASXL3, ATAD1, ATP13A2, ATP1A1, ATP1A2, ATP1A3, ATP6V1A, ATRX, BCKDK, BRAT1, BTD, C12ORF57, CACNA1A, CACNA1B, CACNA1D, CACNA1E, CACNA1G, CACNA1H, CACNA2D2, CACNB4, CAD, CAMK2B, CARS2, CASK, CASR, CC2D1A, CDK9, CDKL5, CERS1, CHD2, CHRNA2, CHRNA4, CHRNB2, CLCN2, CLCN4, CLN3, CLN5, CLN6, CLN8, CLTC, CNKSR2, CNPY3, CNTNAP2, COA7, COL4A1, COL4A2, COL4A3BP, COQ2, COQ4, COX15, COX6B1, CPLX1, CPT2, CSF1R, CSNK2B, CSTB, CTC1, CTSD, CTSF, CUL4B, CUX2, CYFIP2, CYP27A1, D2HGDH, DARS, DARS2, DCX, DDC, DDX3X, DEAF1, DEGS1, DENND5A, DEPDC5, DHDDS, DHFR, DHPS, DIAPH1, DMXL2, DNAJC5, DNM1, DNM1L, DOCK7, DOLK, DPAGT1, DPM1, DPM2, DPYD, DPYS, DYNC1H1, DYRK1A, EARS2, ECHS1, ECM1, EEF1A2, EFHC1, EIF2B1, EIF2B2, EIF2B3, EIF2B4, EIF2B5, EIF3F, EML1, EPM2A, EPRS, ETFA, ETFB, ETFDH, ETHE1, FA2H, FAM126A, FAR1, FARS2, FDFT1, FDX1L, FGF12, FH, FKTN, FLNA, FOLR1, FOXG1, FOXRED1, FRRS1L, FUT8, GABBR2, GABRA1, GABRB1, GABRB2, GABRB3, GABRG2, GALC, GAMT, GCDH, GCH1, GCSH, GFAP, GFM1, GFM2, GJC2, GLB1, GLDC, GLRB, GLS, GLUD1, GNAO1, GNB1, GNE, GOLGA2, GOSR2, GPAA1, GPHN, GRIA3, GRIA4, GRIK2, GRIN1, GRIN2A, GRIN2B, GRIN2D, GRN, GTPBP3, GUF1, HACE1, HCN1, HCN2, HECW2, HEPACAM, HIBCH, HNRNPU, HSD17B10, HSPD1, HTRA1, HTT, IBA57, ICK, IER3IP1, IFIH1, IQSEC2, IRF2BPL, ITPA, KCNA1, KCNA2, KCNB1, KCNC1, KCNH1, KCNJ10, KCNMA1, KCNQ2, KCNQ3, KCNQ5, KCNT1, KCNT2, KCTD3, KCTD7, KDM5C, KIAA1715, KIAA2022, KIF1A, KIF5A, KIF5C, KMT2E, L2HGDH, LGI1, LIAS, LMNB1, LMNB2, LRPPRC, LYRM7, MACF1, MAGI2, MARS2, MBD5, MBOAT7, MDH2, MECP2, MED12, MED17, MEF2C, MFSD8, MIPEP, MLC1, MOCS1, MOCS2, MRPL44, MTFMT, MTHFR, MTOR, NACC1, NBEA, NDST1, NDUFAF3, NDUFAF5, NDUFAF6, NDUFS2, NDUFS4, NDUFS6, NDUFS7, NDUFS8, NDUFV1, NECAP1, NEU1, NEUROD2, NFU1, NHLRC1, NKX6-2, NOTCH3, NPRL2, NPRL3, NR2F1, NRXN1, NSDHL, NT5C2, NTRK2, NUBPL, NUS1, OCLN, OFD1, OPHN1, P4HTM, PACS1, PACS2, PAFAH1B1, PARS2, PCDH19, PEX1, PEX10, PEX12, PEX13, PEX14, PEX16, PEX19, PEX2, PEX26, PEX3, PEX5, PEX6, PGK1, PHACTR1, PHF6, PIGA, PIGB, PIGC, PIGG, PIGN, PIGO, PIGP, PIGQ, PIGS, PIGT, PIGV, PIGW, PITRM1, PLAA, PLCB1, PLP1, PNKP, PNPO, POLG, POLR3A, POLR3B, PPP2CA, PPP3CA, PPT1, PRICKLE1, PRICKLE2, PRIMA1, PRODH, PROSC, PRRT2, PRUNE, PSAP, PSAT1, PTPN23, PTS, PUM1, PURA, PYCR2, QARS, QDPR, RAB11A, RAB11B, RAB39B, RALA, RARS, RELN, RHOBTB2, RMND1, RNASEH2A, RNASEH2B, RNASEH2C, RNASET2, RNF13, RNF216, ROGDI, RORA, RORB, RUSC2, SAMHD1, SCARB2, SCN1A, SCN1B, SCN2A, SCN3A, SCN8A, SCN9A, SCO1, SDHAF1, SERAC1, SERPINI1, SETBP1, SETD1B, SGSH, SIK1, SLC12A5, SLC13A5, SLC19A3, SLC1A2, SLC1A4, SLC25A1, SLC25A15, SLC25A22, SLC25A42, SLC2A1, SLC35A1, SLC35A2, SLC39A8, SLC46A1, SLC6A1, SLC6A5, SLC6A8, SLC9A6, SMARCA2, SMC1A, SMS, SNAP25, SNORD118, SOX10, SPATA5, SPTAN1, SPTBN4, SSR4, ST3GAL3, ST3GAL5, STRADA, STX1B, STXBP1, SUMF1, SUOX, SYN1, SYNGAP1, SYNJ1, SZT2, TAF1, TANGO2, TBC1D20, TBC1D24, TBCD, TBCE, TBCK, TBL1XR1, TCF4, TK2, TPK1, TPP1, TRAK1, TREX1, TRIM8, TRIT1, TSC1, TSC2, TSFM, TTC19, TUBA1A, TUBB2A, TUBB2B, TUBB4A, UBA5, UBE2A, UBE3A, UBTF, UNC80, VAMP2, VARS, VPS13A, WARS2, WASF1, WDR26, WDR45, WWOX, YWHAG, YY1, ZDHHC9, ZEB2, ZFYVE26, ZNHIT3, ZSWIM6.

How is genetic testing for epilepsy conducted?

The sample for genetic testing is typically EDTA blood. The sample is then analyzed using the NGS method, which enables precise and rapid identification of potential genetic mutations linked to epilepsy. Test results are generally available within 4 to 6 weeks.

What results can you expect from genetic testing?

The results of genetic testing may be:

• Positive: A mutation associated with epilepsy has been identified.
• Negative: No known mutation associated with epilepsy was found.
• Variant of uncertain significance: A mutation was detected, but its relevance to epilepsy is unclear.

Each analysis includes a personalized report from a geneticist, and you can also schedule a genetic counseling session at our laboratory.

Will genetic testing help my doctor and me choose the best treatment?

In many cases, genetic testing can assist your doctor in identifying the most effective treatment for epilepsy. For example, certain genetic mutations may indicate that a patient could benefit from specific medications or therapies, while other mutations might suggest avoiding particular treatments.

Should everyone with epilepsy consider an epilepsy panel?

There isn’t a one-size-fits-all answer to this question. The decision to undergo genetic testing depends on several factors, including the type of epilepsy, the patient’s age at the onset of seizures, and the family history of the condition. It’s important for patients to discuss with their doctors to evaluate the need for testing.

Should my family members get tested?

If genetic testing reveals a mutation that could be inherited, family members might also consider testing to determine if they carry the same mutation. This can be helpful in assessing the risk of epilepsy in other family members and for future planning, particularly in relation to reproductive counseling.

Advanced genetic panels at IntroLab

IntroLab offers advanced genetic panels that use NGS technology to identify various hereditary diseases.

• Autoinflammatory diseases panel
• Cardiomyopathy panel
• Arrhythmia panel
• Marfan syndrome panel
• Clinical exome sequencing
• Molecular karyotyping

As part of its prenatal services, IntroLab provides tests that enable early detection of genetic and chromosomal abnormalities in the fetus.

• Prenatal BASIC Test
• Prenatal PLUS Test
• Prenatal EXPERT Test
• Prenatal PREMIUM Test
• Prenatal SPECIAL Test
• Prenatal SPECIAL + SMA Test

These tests offer parents and doctors crucial information, allowing for better planning of prenatal care.