Geneting testing: Epilepsy panel
 
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Neurology – Epilepsy panel

a-    Background

Epilepsy is a common neurological disorder characterized by recurrent seizures. It has an estimated prevalence of about 0.08% and a lifetime cumulative incidence of about 3%.

Approximately 60% of epilepsy cases have no cause other than a genetic predisposition, while the rest are due to a major acquired cause.

However, the probability of a genetic cause of epilepsy is often underestimated in routine clinical practice. Thus, genetic testing can be useful in order to facilitate appropriate counseling. In some patients, it can also help guiding the treatment and predict the risk of being affected for asymptomatic relatives.

b-   How does it work ?

  • Stage 1: Patient identification
    Discussion of personnal and family history
    Eplanation of genetic testing options
  • Stage 2: Sample submission
    The patient’s sample and necessary paperwork are sent to the laboratory
  • Stage 3: Genetic testing
    At the laboratory, genetic testing for most genes includes next-generation sequencing and/or exon aray analysis
  • Stage 4: Genetic test results
    Contains information on the results of the genetic test and available medical management options.
    The final report is sent to the ordering Incorpore specialist
  • Stage 5: Post-test discussion
    Incorpore specialist discusses the test resutls, medical management options, and implication for family members with the patient

c-   To whom it is recommended?

  • Individuals with a confirmed diagnosis of epilepsy and/or suspected genetic cause of epilepsy (epileptic seizures occurring at a young age, family history, etc.)
  • Relatives of an index case tested positive for a mutation-causing disease

d-   Why choose this assay?

Test Benefits

Benefits of this test are:

  • The diagnosis confirmation of a specific genetic syndrome of epilepsy
  • The diagnosis refinement, e.g. determination of an unequivocal genetic cause in case of inconclusive clinical picture / atypical phenotype, discrimination between syndromic and non-syndromic form of epilepsy, etc.
  • Treatment guidance and targeted management
  • The subsequent identification of affected relatives in families where a disease causing mutation has already been found. This would allow an earlier management of at-risk family members.

Risk Management

Risk and treatment management includes, but is not limited to :

For ALDH7A1 related pyridoxine-dependent epilepsy and PNPO related pyridoxamine 5′-phosphate oxidase deficiency:

Treatment

  • Pyridoxine should be used

For KCNQ2 related early infantile epileptic encephalopathy / neonatal benign seizures:

Treatment

  • Retigabine (or Ezogabine) specifically targets and modulates the opening of the involved potassium channels. However its safety and efficacy in children still need to be assessed.

For PRRT2 related infantile convulsions with paroxysmal choreoathetosis/ episodic kinesigenic dyskinesia / infantile benign seizures:

Treatment

  • Carbamazepine or oxcarbazepine might be effective

Management

  • Patients should be monitored for other neurological manifestations

For SCN1A related Dravet syndrome / GEFSP2 / familial hemiplegic migraine:

Treatment

  • Some sodium channel agents such as phenytoin, carbamazepin and lamotrigine should be avoided

Management

  • Monitoring and management of progressive changes in gait
  • Awareness of risk of sudden unexplained death in epilepsy

For SLC2A1 related GLUT1 deficiency syndrome:

Treatment

  • Ketogenic diet should be tried

Management

  • Patients should be monitored for movement disorder

 e–   What is investigated?

Panel composition

Gene MIM Gene Related disease / Phenotype MIM Phenotype
ALDH7A1 107323 Epilepsy, pyridoxine-dependent 266100
BMPR1A 601299 Juvenile polyposis syndrome 174900
ALG13 300776 Congenitale disorder of glycosylation, type IS 300884
ARHGEF9 300429 Epileptic encephalopathy, early infantile. 8 300607
CDKL5 300203 Epileptic encephalopathy, early infantile. 2 300672
CHD2 602119 Epileptic encephalopathy, childhood-onset 615369
CPA6 609562 Epilepsy, familial temporal lobe, 5 614417
DEPDC5 614191 Epilepsy, familial focal, with variable foci 604364
GABRA1 137160 Epileptic encephalopathy, early infantile. 19 615744
GABRB3 137192 Epilepsy, childhood absence, susceptibility to. 5 612269
GABRD 137163 Epilepsy, idiopathic generalized, susceptibility to. 10 613060
GABRG2 137164 Febrile seizures, familial. 8 611277
GNAO1 139311 >Epileptic encephalopathy, early infantile. 19 615473
GRIN2A 138253 Epilepsy, focal, with speech disorder and with or without mental retardation 245570
HCN1 602780 Epileptic encephalopathy, early infantile. 24 615871
HDAC4 605314 Brachydactyly-mental retardation syndrome 600430
IQSEC2 300522 Mental retardation, X-linked 1 309530
KCNQ2 602235 Seizures benign neonatal, 1/Epileptic encephalopathy, early infantile. 7 121200 613720
KCNQ3 602232 Seizures benign neonatal, type 2 121201
KCNT1 608167 Epilepsy nocturnal frontal lobe, 5/Epileptic encephalopathy, early infantile. 14 615005 614959
KCTD7 611725 Epilepsy, progressive myoclonic 3, with or without intracellular inclusions 611726
LGI1 604619 Epilepsy, familial temporal lobe, 1 600512
MBD5 611472 Mental retardation, autosomal dominant 1 156200
PCDH19 300460 Epileptic encephalopathy, early infantile. 9 300088
PLCB1 607120 Epileptic encephalopathy, early infantile. 12 613722
PNPO 603287 Pyridoxamine 5′- phosphate oxidase deficiency 610090
PRRT2 614386 Episodic kinesigenic dyskinesia 1/Seizures, Benign familial infantile, 2 128200 602066
SCN1A 182389 Dravet syndrome/Epilepsy, generalised, with febril seizures plus, type 2/Migraine, familia hemiplegic, 3 607208 604403 609634
SCN1B 600235 Epilepsy, generalised, with febril seizures plus, type 1 604233
SCN2A 182390 Epileptic encephalopathy, early infantile. 1/Seizures, Benign familial infantile, 3 613721 607745
SCN8A 600702 Epileptic encephalopathy, early infantile. 13 614558
SLC25A22 609302 Epileptic encephalopathy, early infantile. 3 609304
SLC2A1 138140 GLUT1 deficiency syndrome 1&2; Epilepsy, idiopathic generalized, susceptibility to, 12 606777 612126 614847
SLC35A3 605632 Arthrogryposis, mental retardation, and seizures 615553
SPTAN1 182810 Epileptic encephalopathy, early infantile. 5 613477
STXBP1 602926 Epileptic encephalopathy, early infantile. 4 612164
SYNGAP1 603384 Mental retardation, autosomal dominant 5 612621
TBC1D24 613577 Epileptic encephalopathy, early infantile. 16/Myoclonic epilepsy, infantile, familial 615338 605021

 

Technical Details

Methodology

  • Targeted capture of all coding exons and exon-intron boundaries followed by NGS.

 

TAT

5-6 weeks in average. Urgent testing is available upon request.

 

Cost CHF 5’700—

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