Early Infantile Epileptic Encephalopathy NGS Panel

Turnaround Time

8 weeks

CPT Code(s)

81443

Cost

$3,500

Genes

• Dravet syndrome
• Early Infantile Epileptic Encephalopathy
• GLUT1 Deficiency
• Ohtahara Syndrome
• Pyroxidine-dependent Epilepsy
• Raynaud-Claes Syndrome
• West syndrome
• Infantile cerebellar, retinal degeneration
• Lethal neonatal rigidity and multifocal seizure syndrome
• Primary coenzyme Q10 deficiency-7
• Multiple congenital anomalies-hypotonia-seizures syndrome-2
• Microcephaly, seizures, and developmental delay
• Congenital Disorder of Glycosylation type IIm

The panel consists of 86 genes associated with early infantile epileptic encephalopathy. The group of genes included in this panel represent inheritance patterns that are approximately half autosomal dominant and half autosomal recessive plus a few instances of X-linked dominant or recessive conditions. Variants in these genes can be inherited or occur as de novo events. Patients may present in the neonatal period or the first months of life with infantile spasms or overt tonic or myoclonic seizures that may occur up to 100 times per day. EEG findings may be consistent with hypsarrhythmia or burst-suppression patterns. Seizures may be intractable and progressive with subsequent developmental delays and intellectual disability. Neurological signs include spasticity, movement disorders, dystonia, or ataxia. Microcephaly may occur along with changes on brain MRI, and dysphagia or other feeding difficulties may be present. Early death is a risk in these conditions with the most frequent causes being pneumonia or other respiratory compromise or Sudden Unexpected Death in Epilepsy (SUDEP).

Molecular testing is useful to confirm the diagnosis and to identify the disease causing mutations within a family to allow for carrier testing and prenatal diagnosis. Identification of the causative variants may assist with clinical management and potential treatment.

Next Generation Sequencing

The current design of this panel covers all genes and the flanking intronic sequences. This method allows for analysis of greater than 98% of the targeted sequence for the detection of nucleotide substitutions and small deletions and duplications. Large deletions and duplications will not be detected by this panel. Mutations and variants identified on the panel are confirmed with Sanger sequencing. Novel and apparently pathogenic changes are reported when found within the coding region as well as within 10 basepairs of each intron/exon boundary for each gene. Promoter and 3' untranslated sequences are not included in the current analysis. It should be noted that the current protocol is not specifically designed to detect copy number alterations, and single exon deletions may require additional follow-up to determine whether or not they represent technical artifacts. We recommend further array-based testing to more accurately address the concerns of dosage alterations. The Cytogenetic Laboratory at GGC offers a high resolution microarray to complement the sequencing. The GGC Diagnostic Laboratory Directors are available for further consultation regarding the limitations of the NGS and array testing procedures.

The preferred sample type is 3-5 ml of peripheral blood collected in an EDTA (purple top) tube. Extracted DNA and saliva are also accepted for this test. Saliva samples must be submitted in an approved saliva kit. Contact the lab to receive a saliva kit or to have one sent to your patient.

The specimen should be kept at room temperature and delivered via overnight shipping. If shipment is delayed by one or two days, the specimen should be refrigerated and shipped at room temperature. Do not freeze the specimen. Samples collected on Friday can be safely designated for Monday delivery.

If the pathogenic mutation(s) are identified in an affected individual using this panel, prenatal diagnosis is available for future pregnancies. Sanger sequencing will be used for prenatal diagnosis when there is a known familial mutation. Additional fees for cell culture and maternal cell contamination may apply. Maternal cell contamination studies are required for all prenatal molecular tests. Contact the laboratory prior to sending a prenatal specimen.