Unverricht–Lundborg disease (CSTB expansions)

Epilepsy is a common neurological disorder with an estimated prevalence of 5-8 per 1,000 individuals, with a cumulative incidence of 3% (Fiest et al., 2017). The underlying causes of epilepsy are heterogeneous and many. Some forms of epilepsy have an identifiable genetic cause, and every time there are more and more genes that are found to cause some of these forms of epilepsy previously labelled as ‘idiopathic’.

The clinical manifestations of the different forms of epilepsy provide very valuable information when deciding which genetic test to choose, since there are certain epileptic syndromes that will influence the selection of the most appropriate study. We have designed a range of panels that address the most common causes of epilepsy from a genetic point of view, classified according to the epileptic phenotype to carry out a specific diagnostic genetic study, while maintaining a comprehensive panel for more imprecise semiological classifications or more complex cases where it is necessary to cover a wide differential diagnosis.

Different studies of the diagnostic yield of genetic tests in epilepsy report the diagnostic rate to be between 15% and 25% (Mercimek-Mahmutoglu et al., 2015; Wang et al., 2014). Indeed, the diagnostic yield varies depending on patient selection, clinical indications, age, and family history. It is likely that we do not know about many genes involved in epilepsy, but it should be noted that because it is so frequent and heterogeneous, its multifactorial nature must be considered. As an example, studies of carefully selected patients have achieved diagnostic rates of up to 60-70% in early-onset epileptic encephalopathies (Myers et al., 2019).

Genetic tests in epilepsy have traditionally been relegated to complex or refractory patients. However, there are many cost benefits to consider a genetic test among the first few tests ordered for a patient presenting with a form of epilepsy. On the other hand, epilepsy studies increasingly seek not only diagnosis but also an approach to individualized medicine in which the finding of a variant in a certain gene can provide a very valuable aid in selecting the best therapeutic strategy.