Epilepsy global panel [990 genes]

The underlying causes of epilepsy are multiple and heterogeneous. Some forms of epilepsy have an identifiable genetic cause (monogenic), and an increasing number of genes are known to be responsible for some of these forms of epilepsy, which had been previously labeled as ‘idiopathic’ in some cases.

This panel contains 990 genes associated with monogenic epilepsy. It intends to cover a wide phenotypic spectrum of epilepsy, including genes associated with phenotypes where epilepsy is the main clinical feature as well as genes associated with phenotypes where only some of the patients could develop epilepsy.

Thus, the panel includes genes associated with developmental and epileptic encephalopathy, progressive myoclonic epilepsy, and specific epileptic syndromes with a known genetic cause, but also other genes associated with neurodevelopmental disorders, metabolic diseases, malformations of cortical development, or other structural anomalies in which only a subset of patients will develop epilepsy.

Epilepsy is a common neurological disorder with an estimated prevalence of 5-8 per 1000 individuals, with a cumulative lifetime incidence of 3%.

Epilepsy studies increasingly seek not only diagnosis but also an approach to precision medicine in which the finding of a variant in a certain gene can contribute very valuable information for selecting the optimal therapeutic strategy. Moreover, identifying the cause allows providing the patients and/or their families with targeted genetic counseling.

Genetic testing for epilepsy is indicated in patients with:

• Childhood onset and severe epilepsy (particularly developmental and epileptic encephalopaties).
• Family history (in first-degree relatives).
• Drug-resistant epilepsy.
• Additional symptoms (e.g. intellectual disability or other neurodevelopmental disorders, malformations of cortical development, dysmorphias).
• Specific syndromes with a known genetic cause (e.g. self-limited neonatal epilepsy, self-limited infantile epilepsy, sleep-related frontal lobe hypermotor epilepsy, temporal lobe epilepsy with auditory features, familial focal epilepsy with variable foci, or genetic epilepsy with febrile seizures plus).
• Epilepsy surgery (pre-surgical study).

Different studies on the diagnostic yield of genetic testing in epilepsy have reported diagnostic rates between 15% and 25%. Of course, diagnostic yield varies depending on patient screening, clinical indications, age, and family history. As an example, studies performed on carefully selected patients have achieved diagnostic rates up to 60-70% in early-onset epileptic encephalopathies.