Test 39.
Epilepsy with febrile seizures, GEFS+ and Dravet syndrome

Characteristics of the test : (includes 1 gene) 

SCN1A (OMIM #182389)

Basic characteristics of the clinical phenotype:

Familial febrile seizures (FS +) - Age-related disease with epileptic seizures in infancy and early childhood. They usually disappear with the growth of the child in later stages of life, but sometimes febrile seizures plus (FS +) persist until a later age (6 years-old). FS provoking factor is high fever, a symptom of upper and lower respiratory tract infections, observed in 85-90% of the cases. The recurrent risk of the disease is 30% higher in a family with first degree sick relatives than the general population.

Generalized epilepsy with febrile seizures plus (GEFS + syndrome). When febrile generalized tonic-clonic seizures (GTCS) persist after the age of 6 and occur in combination with other types of afebrile generalized (myoclonic, atonic, absences) and partial seizures, we speak of generalized epilepsy syndrome with febrile seizures plus (GEFS + syndrome). The onset of seizures is between  6-months and 6 years of age. Psychomotor development is normal. GEFS + syndrome is characterized by spontaneous disappearance of seizures in later stages of the patient's life and preserved psychomotor development.

Severe myoclonic epilepsy in childhood (Dravet syndrome) - characterized by normal initial psychomotor development. The first manifestations are observed before 12 months of age, most often between 5 and 8 months of age, with fever-provoked generalized seizures. Between 1 and 4 years of age, another types of seizures are observed - myoclonic, atypical absences, tonic, etc. After the second year, there is a start of gradual decline of intellectual and motor development. Point mutations in the SCN1A gene are found in about 10% of patients with GEFS + syndrome, while the proportion of mutations in SCN1A in patients with Dravet syndrome is about 70-80%. 90% of the mutations in the SCN1A gene in Dravet syndrome cases occur de novo, and only 10% are inherited.

Reasons for referring:

All patients with simple/generalized febrile seizures in early childhood and suspected FS+ - sporadic or familial; presence of generalized tonic-clonic seizures and suspicion of GEFS + syndrome; presence of generalized tonic-clonic seizures, myoclonic seizures with gradual regression in intellectual development and suspicion of severe myoclonic epilepsy in childhood (SMEI / Dravet syndrome), and no point mutation by direct sequencing in SCN1A gene has been detected.

Interpretation of results:

  • The detection of mutation by MLPA analysis in the SCN1A gene allows to make the diagnosis of Dravet syndrome, which is useful for the choice of proper epileptic treatment, in order to avoid aggravation of seizures. 

  • Genetic diagnosis will allow assessment of the recurrent risk for transmitting the pathogenic mutation to the future generations.

  • The genetic counselor will interpret and answer all questions about your result.

Method: MLPA (Multiplex- Ligation dependent Probe Amplification)

MLPA analysis is a semi-quantitative method for determining copy number variations of DNA. The methodology is used to detect intragenic or whole-gene deletions or duplications. The analysis for searching for large SCN1A gene deletions or insertions is performed using the kit SALSA MLPA KIT P137-B2 SCN1A, developed by MRC-Holland (Amsterdam, Holland).

Additionally, the laboratory proposes sequencing of the SCN1A gene with subsequent MLPA analysis to exclude all genetic mutations affecting this gene (Test № 33).

In the presence of a complex epileptic phenotype in combination with mental retardation, autistic behavior and dysmorphic features, comprehensive genomic screening by microarray analysis (Tests № 130, 131) and/or next-generation sequencing (NGS) of a specific panel of genes depending on of specific clinical features (Tests № 40, 41, 42, 43, 44) is recommended.

Sensitivity of the method: 90%

What does the test involve?

• DNA isolation and sample storage.

• MLPA analysis of target genes / gene regions to detect pathogenic copy number variations.

• Forming a written result from the genetic test.

• Diagnostic interpretation of results and genetic counseling.

Biological material: Venous blood or DNA

For more information, please read "Biological Sample Requirements and Transport Information" carefully.

Sensitivity of the method: 90%

What does the test involve?

• DNA isolation and sample storage.

• MLPA analysis of target genes / gene regions to detect pathogenic copy number variations.

• Forming a written result from the genetic test.

• Diagnostic interpretation of results and genetic counseling.

Biological material: Venous blood or DNA

For more information, please read "Biological Material Requirements and Transport Information" carefully


SCN1A
Order Online:
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Test Price:
220 BGN
Deadline:
15 working days