GeneDx, Childhood-Onset Epilepsy

Collect at NMCP only Mon-Thursday by 1200

542

Genetic Testing for Epilepsy: Childhood Epilepsy Panel Sequence Analysis* and Exon-Level Deletion/Duplication Testing** of 50 Genes

Whole blood in EDTA. Adults: 8-10 ml; Children: 4 ml; Infants: 2 ml.

Ship overnight at ambient temperature, using a cool pack in hot weather. Specimens may be refrigerated for 7 days prior to shipping.

ambient

14-16 weeks

Epilepsy is defined by the occurrence of at least two unprovoked seizures occurring more than 24 hours apart. It is a common neurological disorder that affects at least 0.8% of the population. The International League against Epilepsy (ILAE) classifies seizures into two main categories.1 Generalized epileptic seizures originate in and rapidly engage both cerebral hemispheres. Tonic-clonic, absence, myoclonic, clonic, tonic, and atonic seizures are all types of generalized seizures. Focal seizures originate from neuronal networks within a single hemisphere. Traditionally, focal seizures have been classified as “simple partial seizures,” which do not result in an alteration of consciousness, and “complex partial seizures,” which cause a change in behavior or consciousness. Some types of seizures, such as infantile spasms, do not fit into either category and remain unclassified. Seizures can be self-limiting or controlled by standard therapeutic treatments in some cases; however, individuals with epileptic encephalopathy have severe seizures that are refractory to treatment, leading to cognitive and behavioral impairment secondary to the epileptic activity. Epilepsy may be an isolated neurological symptom, or it may occur in association with other neurological symptoms or medical problems.2 Some individuals with epilepsy are diagnosed with an electroclinical syndrome such as febrile seizures plus (FS+) based on the presence of characteristic EEG findings and the clinical and family history.1 Genetics: Epilepsy can be caused by genetic disorders, metabolic diseases, trauma, infection, and structural brain abnormalities, although the cause is not known in many cases. A genetic etiology underlies epilepsy in approximately 40% of individuals.3 Genes have been identified that cause both generalized seizures and focal seizures, as well as unclassified epilepsy types such as infantile spasms. The genetic etiology of idiopathic generalized epilepsy (IGE) is frequently complex because it is due to a combination of multiple genetic factors that each confer a small risk for epilepsy and may be modified by environmental influences.3 Currently, approximately 2% of patients with IGE harbor an identifiable mutation in a single gene associated with Mendelian inheritance of epilepsy.4 However, the percentage of patients with Mendelian epilepsy is higher for specific epilepsy types such as generalized epilepsy with febrile seizures plus (GEFS+), Lafora disease, and others.3,5,6,7 The inheritance pattern can be autosomal dominant, autosomal recessive, or X-linked. Mutations in a single gene may be associated with different types of seizures (clinical heterogeneity), and conversely, mutations in different genes can cause the same epilepsy phenotype (genetic heterogeneity). The Childhood Epilepsy Panel includes sequencing and deletion/duplication analysis of 50 genes causing Mendelian forms of epilepsy. Many of these genes encode subunits of ion channels involved in stabilizing or propagating neuronal activity, including components of the voltage-gated sodium and calcium channels and the ligand-gated gamma-aminobutyric (GABA) and nicotinic acetylcholine receptor channels.5,6,7,8 It also includes non-ion channel genes associated with neurotransmitter, storage, and other neurometabolic disorders, as well as genes causing syndromic forms of epilepsy, many of which are involved in transcriptional activation or repression.5,6,9,10,11