Characteristics of the test : (includes 1 gene)
KCNQ2 (OMIM #602235)
Basic characteristics of the clinical phenotype:
Benign familial neonatal convulsions, neonatal-infantile convulsions (BFNC, BFNIC) – both types of epilepsy are sporadic or familial with autosomal dominant inheritance. The seizures are heterogeneous and short. Focal or generalized, tonic-clonic convulsions, with or without cyanosis, are predominant. A characteristic feature of both electro-clinical syndromes is the spontaneous disappearance of seizures later in life. The difference between BFNC and BFNIC is the initial age of the attacks - BFNCs begin in the first week after birth, while BFNICs start within the first 4 months of life.
Early-onset epileptic encephalopathy (EIEE7) - an autosomal dominant disease characterized by refractory seizures beginning in childhood and resulting in delayed neuropsychological development. Seizures usually regress by the age of 3-4 with improvement in EEG and MRI abnormalities, but the severe neurological deficits persist.
In about 80% of patients with BFNC and BFNIC, a point mutation is found in KCNQ2 gene, while the proportion of deletions / duplications in this gene is smaller - 20-40%.
Reasons for referring:
All patients with tonic, tonic-clonic, focal or generalized, with or without cyanosis seisures and their onset in the first week after birth - suspected benign familial neonatal convulsions (BFNC); presence of tonic, tonic-clonic, focal or generalized, with or without cyanosis seizures and their onset in the first 4 months of life - suspected benign familial neonatal-infantile seizures (BFNIC); presence of a family history of epileptic disease in neonatal or early childhood; suspected early-onset epileptic encephalopathy 7 (EIEE7) combined with neurodevelopmental delay and persistent neurological disorders.
Interpretation of results:
The detection of mutation in the KCNQ2 gene allows the diagnosis of benign familial neonatal convulsions, neonatal-infantile convulsions (BFNC, BFNIC), or more severe EE Early-onset epileptic encephalopathy (EIEE7).
Genetic diagnosis allows an adequate prognosis depending on the type of mutation and the severity of the disease. In BFNC and BFNIC, spontaneous disappearance of seizures is observed in the later stages of the child's development, in contrast to EIEE7, where neurodevelopmental prognosis is poor.
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: Sanger sequencing (ABI 3130xl)
The method involves bidirectional DNA sequencing of all coding exons and intron-exon boundaries of the KCNQ2 gene. The laboratory offers single exon sequencing in relatives of patients to determine the carrier status in cases where the KCNQ2 mutation is known (Test № 128).
When no point KCNQ2 mutations are detected by this method, it is recommended to look for larger KCNQ2 deletions/insertions affecting parts of or whole exons by the hybridization-based MLPA method (Test № 35). The laboratory proposes sequencing of the KCNQ2 gene with subsequent MLPA analysis to exclude all genetic mutations affecting this gene (Test № 36).
In the presence of a complex epileptic phenotype in combination with intellectual disability, 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: 99.5%
What does the test involve?
• DNA isolation and sample storage.
• Direct sequencing of target genes / gene regions to detect pathogenic mutations.
• 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.
