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 Health and Prevention Center specialist
• Stage 5: Post-test discussion
  Health and Prevention Center 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—